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CompletedNCT03118570AsteroidUpdated Jul 5, 2023Results posted

A Study in Adult Patients With Type I, III or IV Osteogenesis Imperfecta Treated With BPS804

A Phase 2 interventional study of setrusumab and Calcium in Osteogenesis Imperfecta, Type I, Osteogenesis Imperfecta Type III and Osteogenesis Imperfecta Type IV, sponsored by Ultragenyx Pharmaceutical Inc. Completed at 25 sites in 5 countries. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-07-05.

Sponsored by Ultragenyx Pharmaceutical Inc · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
112
Allocation
Randomized
Ages
18 Years to 75 Years
Sex
All
01

Study summary

The purpose of this study is to select a suitable dose of BPS804 by measuring the strength/quality of bone using a special type of CT scanner. Participants will be treated for 12 months and followed up for a further 12 months.

Read the detailed description

This study was previously posted by Mereo Biopharma and was transferred to Ultragenyx in February 2021.

02

Conditions studied

  • Osteogenesis Imperfecta, Type I
  • Osteogenesis Imperfecta Type III
  • Osteogenesis Imperfecta Type IV

Keywords

  • Osteogenesis Imperfecta
  • Brittle Bone Disease
03

Who can participate

Ages eligible
18 Years to 75 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Patients with a clinical diagnosis of OI Type I, III or IV with a confirmed defect in the COL1A1/COL1A2 genes, as confirmed by genetic testing
  • One or more fractures in the past 5 years
  • Capable of giving signed consent

Exclusion criteria

Exclusion Criteria:

  • History of skeletal malignancies or other bone diseases (other than OI)
  • History of neural foraminal stenosis (except if due to scoliosis)
  • History of myocardial infarction, angina pectoris, ischaemic stroke or transient ischaemic attack
  • History of endocrine or thyroid/parathyroid conditions that could affect bone metabolism
  • Treatment with bisphosphonates within 3 months of randomisation
  • Treatment with teraparatide, denosumab or other anabolic/anti-reabsorptive medications within 6 months of randomisation
04

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Investigator)
Enrollment
112 participants (actual)

Study arms

  • Experimental
    Setrusumab 20 mg/kg (Blinded)

    Setrusumab 20 mg/kg intravenous (IV) infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

    Drug: setrusumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D · Drug: zoledronic acid (optional)

  • Experimental
    Setrusumab 8 mg/kg (Blinded)

    Setrusumab 8 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

    Drug: setrusumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D · Drug: zoledronic acid (optional)

  • Experimental
    Setrusumab 2 mg/kg (Blinded)

    Setrusumab 2 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

    Drug: setrusumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D · Drug: zoledronic acid (optional)

  • Experimental
    Setrusumab 20 mg/kg (Open-Label)

    Setrusumab 20 mg/kg IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

    Drug: setrusumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D · Drug: zoledronic acid (optional)

  • Placebo comparator
    Placebo

    Placebo IV infusion once a month for 12 months plus 500 mg calcium oral tablets and 800 IU vitamin D capsules.

    Dietary Supplement: Calcium · Dietary Supplement: Vitamin D

Interventions

  • Drugsetrusumab

    Intravenous infusion

    Also known as: BPS804

  • Dietary supplementCalcium

    tablets

  • Dietary supplementVitamin D

    capsules

  • Drugzoledronic acid (optional)

    Following completion of the study treatment (Month 12) participants can receive an optional single dose of zoledronic acid. Participants can receive an optional further dose of zoledronic acid at Month 18 at the discretion of their treating physician.

05

What researchers measure

Primary outcomes

  1. Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12

    Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).

    Time frame: Baseline, Month 12 (end of treatment [EOT])

  2. Change From Baseline in Radial Bone Strength (Failure Load) at Month 12

    Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Month 12 (EOT)

  3. Change From Baseline in Radial Bone Strength (Stiffness) at Month 12

    Assessed by FEA of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Month 12 (EOT)

Secondary outcomes

  1. Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set

    Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

    Time frame: Baseline, Months 6, 12 (EOT), 18, 24

  2. Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm

    Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

    Time frame: Baseline, Months 6, 12 (EOT)

  3. Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set

    Assessed by FEA of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Months 6, 12 (EOT), 18, 24

  4. Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm

    Assessed by FEA of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Months 6, 12 (EOT)

  5. Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set

    Assessed by FEA of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Months 6, 12 (EOT), 18, 24

  6. Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm

    Assessed by FEA of models generated from HRpQCT images of the distal radius.

    Time frame: Baseline, Months 6, 12 (EOT)

  7. Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12

    Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis.

    Time frame: Month 12 (EOT)

  8. Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6

    BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.

    Time frame: Baseline, Month 6

  9. Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6

    BMD was evaluated by DXA.

    Time frame: Baseline, Month 6

  10. Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12

    BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.

    Time frame: Baseline, Month 12 (EOT)

  11. Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12

    BMD was evaluated by DXA.

    Time frame: Baseline, Month 12 (EOT)

  12. Change From Baseline in Total vBMD (Radial and Tibial) Over Time

    Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

    Time frame: Baseline, Months 6, 12 (EOT), 18, and 24

  13. Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time

    Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

    Time frame: Baseline, Months 6, 12 (EOT), 18, and 24

  14. Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set

    Time frame: Baseline, Month 6, Month 12 (EOT)

  15. Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12

    Lean and fat body mass was evaluated using whole body DXA (including the head).

    Time frame: Baseline, Months 6, 12 (EOT)

  16. Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12

    Time frame: Baseline, Months 1, 3, 6, 9, 12 (EOT)

  17. Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12

    Time frame: Baseline, Months 1, 3, 6, 9, 12 (EOT)

  18. Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12

    The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning.

    Time frame: Baseline, Months 6, 12 (EOT)

  19. Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12

    The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning.

    Time frame: Baseline, Months 6, 12 (EOT)

  20. Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12

    The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is "no problems" and 5 is "extreme problems". The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health).

    Time frame: Baseline, Months 6 and 12 (EOT)

  21. Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12

    The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life.

    Time frame: Baseline, Months 6, 12 (EOT)

  22. Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12

    The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain.

    Time frame: Baseline, Months 6, 12 (EOT)

  23. Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12

    The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty.

    Time frame: Baseline, Months 6, 12 (EOT)

  24. Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14

    Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor.

    Time frame: up to Month 14

  25. Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death

    An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a "reasonable possibility" of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication.

    Time frame: Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)

06

Results

Posted Mar 2, 2022

Participant flow

Participant flow — Overall Study
MilestoneSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)Placebo
Started312930220
Reassigned from placebo to 20 mg/kg open-label setrusumab000019
Completed262225215
Not completed57505
Withdrew: Adverse event20003
Withdrew: Withdrawal by subject01401
Withdrew: Lost to follow-up23101
Withdrew: Other, not specified13000

Outcome measures

PrimaryChange From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12

Assessed by high resolution peripheral quantitative computed tomography (HRpQCT). HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presents the ratio of the means between the visit and Baseline from analysis of covariance (ANCOVA).

Time frame:
Baseline, Month 12 (end of treatment [EOT])
Reported as:
Number · ratio
Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 12
ratioSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Change From Baseline in Radial Trabecular Volumetric Bone Mineral Density (Tr vBMD) at Month 121.004 (0.987 to 1.021)0.993 (0.975 to 1.012)0.992 (0.974 to 1.011)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.644 (Analysis is based on a log transformed analysis of covariance (ANCOVA) model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.485 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.404 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
PrimaryChange From Baseline in Radial Bone Strength (Failure Load) at Month 12

Assessed by finite element analysis (FEA) of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Month 12 (EOT)
Reported as:
Least squares mean · newton (N)
Change From Baseline in Radial Bone Strength (Failure Load) at Month 12
newton (N)Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Change From Baseline in Radial Bone Strength (Failure Load) at Month 1261.25 ± 21.66932.25 ± 24.3428.86 ± 23.200
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.006 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.190 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.704 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
PrimaryChange From Baseline in Radial Bone Strength (Stiffness) at Month 12

Assessed by FEA of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Month 12 (EOT)
Reported as:
Least squares mean · N/mm
Change From Baseline in Radial Bone Strength (Stiffness) at Month 12
N/mmSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Change From Baseline in Radial Bone Strength (Stiffness) at Month 121638.70 ± 625.8081422.00 ± 703.275209.89 ± 671.777
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.011 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.047 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.756 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set

Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

Time frame:
Baseline, Months 6, 12 (EOT), 18, 24
Reported as:
Number · ratio
Change From Baseline in Radial and Tibial Tr VBMD Over Time: Full Analysis Set
ratioSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Radial: Month 61.007 (0.993 to 1.021)1.000 (0.986 to 1.015)0.998 (0.984 to 1.013)
Radial: Month 121.004 (0.987 to 1.021)0.993 (0.975 to 1.012)0.992 (0.974 to 1.011)
Radial: Month 181.002 (0.984 to 1.020)0.992 (0.973 to 1.013)0.979 (0.962 to 0.997)
Radial: Month 240.997 (0.972 to 1.023)0.998 (0.970 to 1.027)0.979 (0.951 to 1.008)
Tibial: Month 61.004 (0.986 to 1.022)1.016 (0.996 to 1.036)0.990 (0.969 to 1.012)
Tibial: Month 120.991 (0.940 to 1.046)1.018 (0.955 to 1.086)0.973 (0.909 to 1.042)
Tibial: Month 180.989 (0.945 to 1.035)1.042 (0.985 to 1.102)0.983 (0.933 to 1.036)
Tibial: Month 241.000 (0.949 to 1.054)1.062 (0.995 to 1.133)1.017 (0.949 to 1.090)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.329 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.953 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.795 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.644 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.485 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.404 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.827 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.459 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.022 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.821 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.911 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.152 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.668 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.109 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.358 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.742 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.567 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.430 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.634 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.146 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.521 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.991 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.069 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.625 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChanges From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm

Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Number · ratio
Changes From Baseline in Radial and Tibial Tr VBMD at Months 6 and 12: Open-Label Arm
ratioSetrusumab 20 mg/kg (Open-Label)
Radial: Month 60.994 (0.972 to 1.017)
Radial: Month 121.011 (0.986 to 1.036)
Tibial: Month 61.013 (0.991 to 1.035)
Tibial: Month 121.035 (0.975 to 1.099)
Statistical analysis
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.615 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.376 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.259 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.253 (Analysis is based on a log transformed ANCOVA model with change from baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChanges From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set

Assessed by FEA of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Months 6, 12 (EOT), 18, 24
Reported as:
Least squares mean · N
Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) Over Time: Full Analysis Set
NSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Radial: Month 631.22 (-1.80 to 64.23)39.95 (6.63 to 73.27)-3.28 (-36.57 to 30.00)
Radial: Month 1261.25 (18.03 to 104.46)32.25 (-16.30 to 80.80)8.86 (-37.41 to 55.13)
Radial: Month 1850.39 (19.11 to 81.68)43.11 (6.79 to 79.42)-10.53 (-41.86 to 20.80)
Radial: Month 24-19.59 (-72.66 to 33.47)45.03 (-14.40 to 104.47)-50.65 (-108.69 to 7.39)
Tibial: Month 646.00 (-24.91 to 116.92)45.91 (-28.16 to 119.98)-65.33 (-146.39 to 15.72)
Tibial: Month 1276.15 (-11.23 to 163.54)60.20 (-42.63 to 163.04)-65.96 (-175.43 to 43.51)
Tibial: Month 1850.69 (-34.55 to 135.93)88.33 (-13.67 to 190.32)-49.50 (-144.93 to 45.94)
Tibial: Month 24-24.75 (-126.76 to 77.27)41.37 (-86.68 to 169.43)-74.94 (-208.22 to 58.34)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.064 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.019 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.845 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.006 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.190 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.704 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.002 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.021 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.504 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.462 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.134 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.086 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.199 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.219 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.112 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.086 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.245 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.232 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.237 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.088 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.302 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.626 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.517 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.262 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChanges From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm

Assessed by FEA of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · N
Changes From Baseline in Radial and Tibial Bone Strength (Failure Load) at Months 6 and 12: Open-Label Arm
NSetrusumab 20 mg/kg (Open-Label)
Radial: Month 6110.16 (61.30 to 159.01)
Radial: Month 1288.32 (28.55 to 148.09)
Tibial: Month 669.78 (-8.61 to 148.18)
Tibial: Month 12112.92 (10.76 to 215.07)
Statistical analysis
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.004 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.080 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = 0.031 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChanges From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set

Assessed by FEA of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Months 6, 12 (EOT), 18, 24
Reported as:
Least squares mean · N/mm
Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) Over Time: Full Analysis Set
N/mmSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Radial: Month 6795.67 (-34.71 to 1626.04)1048.61 (209.47 to 1887.75)109.65 (-728.52 to 947.82)
Radial: Month 121638.70 (390.57 to 2886.83)1422.00 (19.37 to 2824.64)209.89 (-1129.93 to 1549.71)
Radial: Month 181295.98 (390.54 to 2201.42)803.50 (-263.21 to 1870.21)-215.92 (-1132.78 to 700.94)
Radial: Month 24-625.46 (-1888.53 to 637.60)1172.45 (-265.87 to 2610.76)-1258.55 (-2663.69 to 146.60)
Tibial: Month 61344.84 (-296.83 to 2986.52)1051.40 (-708.46 to 2811.25)-1356.71 (-3284.14 to 570.73)
Tibial: Month 122326.63 (221.71 to 4431.55)1543.85 (-973.70 to 4061.40)-1428.87 (-4118.78 to 1261.03)
Tibial: Month 181047.16 (-1070.79 to 3165.11)1697.21 (-861.80 to 4256.23)-815.38 (-3247.85 to 1617.09)
Tibial: Month 24-1250.69 (-4131.64 to 1630.26)622.77 (-2966.46 to 4212.01)-1844.84 (-5695.04 to 2005.37)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.060 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.015 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.795 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.011 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.047 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.756 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.006 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.137 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.639 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.325 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.108 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.078 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.106 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.236 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.164 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.031 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.224 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.291 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.324 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.188 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.503 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.385 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.727 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.338 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChanges From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm

Assessed by FEA of models generated from HRpQCT images of the distal radius.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · N/mm
Changes From Baseline in Radial and Tibial Bone Strength (Stiffness) at Months 6 and 12: Open-Label Arm
N/mmSetrusumab 20 mg/kg (Open-Label)
Radial: Month 65056.51 (3404.58 to 6708.45)
Radial: Month 124992.82 (3056.80 to 6928.84)
Tibial: Month 64225.92 (1840.16 to 6611.68)
Tibial: Month 125827.81 (2601.54 to 9054.08)
Statistical analysis
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Open-Label) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryPercentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12

Fracture assessment, confirmed by central radiographic reading, was carried out for peripheral including all major long bones, minor bone (digits, ribs) and vertebral fractures. Fractures without clinical symptoms, detected only by means of radiographic investigations, were not included in the analysis.

Time frame:
Month 12 (EOT)
Reported as:
Number · percentage of participants
Percentage of Participants With at Least 1 New Fracture (Peripheral, Vertebral, Long-Bone, Any) at Month 12
percentage of participantsSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Peripheral6.517.213.3
Vertebral000
Long-Bone3.213.83.3
Any16.134.523.3
SecondaryChange From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6

BMD was evaluated by dual-energy x-ray absorptiometry (DXA). T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.

Time frame:
Baseline, Month 6
Reported as:
Least squares mean · T-score
Change From Baseline in Lumbar, Total Body, and Femoral Neck Bone Mineral Density (BMD) T-score at Month 6
T-scoreSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Lumbar0.273 (0.142 to 0.405)0.338 (0.213 to 0.464)0.110 (-0.014 to 0.233)
Total Body0.072 (-0.049 to 0.194)0.071 (-0.048 to 0.189)0.122 (0.009 to 0.235)
Femoral Neck-0.024 (-0.143 to 0.095)0.102 (-0.023 to 0.226)0.087 (-0.026 to 0.199)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.080 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.238 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.238 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.035 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.687 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.107 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.128 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6

BMD was evaluated by DXA.

Time frame:
Baseline, Month 6
Reported as:
Least squares mean · g/cm^2
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 6
g/cm^2Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Lumbar4.06 (2.12 to 6.00)4.70 (2.86 to 6.55)1.58 (-0.24 to 3.40)
Total Body0.77 (-0.38 to 1.92)0.83 (-0.29 to 1.94)1.21 (0.14 to 2.28)
Femoral Neck-0.42 (-2.51 to 1.68)1.64 (-0.57 to 3.84)1.61 (-0.38 to 3.59)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.088 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.184 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.144 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.028 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.694 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.143 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.111 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12

BMD was evaluated by DXA. T-Score was calculated based on actual measured bone density value. T-scores are standardized scores that reflect the standard deviations (SDs) above/below the normal mean for young adults. A score of 50 indicates the population mean with a standard deviation of 10. A positive change in DXA T-score indicates an improvement in BMD.

Time frame:
Baseline, Month 12 (EOT)
Reported as:
Least squares mean · T-score
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD T-score at Month 12
T-scoreSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Lumbar0.587 (0.427 to 0.746)0.486 (0.324 to 0.648)0.174 (0.022 to 0.327)
Total Body0.181 (0.051 to 0.310)0.199 (0.068 to 0.330)0.108 (-0.015 to 0.231)
Femoral Neck0.163 (0.008 to 0.319)0.159 (-0.007 to 0.326)0.104 (-0.053 to 0.260)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.026 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.007 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.004 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.085 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.040 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.061 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.189 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12

BMD was evaluated by DXA.

Time frame:
Baseline, Month 12 (EOT)
Reported as:
Least squares mean · g/cm^2
Change From Baseline in Lumbar, Total Body, and Femoral Neck BMD at Month 12
g/cm^2Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Lumbar8.55 (6.13 to 10.97)6.79 (4.34 to 9.25)2.50 (0.19 to 4.81)
Total Body1.98 (0.70 to 3.25)2.03 (0.73 to 3.33)1.06 (-0.16 to 2.27)
Femoral Neck3.30 (0.64 to 5.96)2.65 (-0.20 to 5.51)1.90 (-0.77 to 4.56)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.035 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.003 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.003 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.088 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.016 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.068 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.160 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Total vBMD (Radial and Tibial) Over Time

Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

Time frame:
Baseline, Months 6, 12 (EOT), 18, and 24
Reported as:
Number · ratio
Change From Baseline in Total vBMD (Radial and Tibial) Over Time
ratioSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Radial, Month 61.011 (0.999 to 1.022)0.995 (0.984 to 1.007)1.000 (0.989 to 1.012)
Radial, Month 121.017 (1.006 to 1.029)1.008 (0.995 to 1.021)0.999 (0.986 to 1.011)
Radial, Month 181.013 (1.000 to 1.026)0.992 (0.978 to 1.007)0.996 (0.983 to 1.009)
Radial, Month 240.998 (0.984 to 1.012)1.009 (0.994 to 1.025)0.985 (0.969 to 1.000)
Tibial, Month 61.017 (1.001 to 1.033)1.011 (0.995 to 1.028)0.995 (0.977 to 1.031)
Tibial, Month 121.024 (1.004 to 1.045)1.011 (0.988 to 1.035)0.989 (0.965 to 1.014)
Tibial, Month 181.020 (0.997 to 1.045)1.021 (0.992 to 1.050)0.987 (0.961 to 1.014)
Tibial, Month 241.001 (0.982 to 1.021)1.025 (1.001 to 1.050)0.994 (0.970 to 1.019)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.065 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.405 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.966 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.003 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.229 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.807 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.042 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.283 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.536 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.765 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.247 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.050 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.037 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.174 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.558 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.020 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.346 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.387 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.093 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.156 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.324 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.920 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.040 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.643 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Cortical vBMD (Radial and Tibial) Over Time

Assessed by HRpQCT. HRpQCT scans were performed on the participant's distal non-dominant arm. In cases of an arm that had been supported with rods or had significant deformity, the dominant limb was selected. Data presented is the ratio of the means between the Visit and Baseline from ANCOVA.

Time frame:
Baseline, Months 6, 12 (EOT), 18, and 24
Reported as:
Number · ratio
Change From Baseline in Cortical vBMD (Radial and Tibial) Over Time
ratioSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Radial, Month 61.004 (0.997 to 1.010)1.002 (0.996 to 1.009)0.998 (0.992 to 1.005)
Radial, Month 121.005 (0.998 to 1.012)1.003 (0.995 to 1.010)1.001 (0.993 to 1.008)
Radial, Month 181.011 (1.001 to 1.021)1.001 (0.989 to 1.012)1.007 (0.997 to 1.017)
Radial, Month 241.011 (0.999 to 1.022)1.018 (1.005 to 1.031)1.002 (0.989 to 1.015)
Tibial, Month 61.012 (1.003 to 1.022)0.997 (0.987 to 1.007)0.998 (0.987 to 1.008)
Tibial, Month 121.017 (1.008 to 1.026)1.004 (0.993 to 1.014)0.998 (0.987 to 1.009)
Tibial, Month 181.024 (1.009 to 1.039)1.004 (0.986 to 1.022)0.993 (0.976 to 1.009)
Tibial, Month 241.020 (1.004 to 1.035)1.017 (0.998 to 1.036)0.996 (0.976 to 1.017)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.285 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.544 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.615 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.179 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.513 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.849 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.037 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.880 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.153 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.073 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.007 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.791 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.010 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.553 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.652 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.482 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.685 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.002 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.672 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.377 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.015 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.086 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.712 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryNumber of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set
Time frame:
Baseline, Month 6, Month 12 (EOT)
Reported as:
Count of participants · Participants
Number of Participants With Clinically Significant Changes From Baseline in Body Height, Weight and Body Mass Index (BMI) at 6 and 12 Months: Full Analysis Set
ParticipantsSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 6: Body Height000
Month 6: Weight000
Month 6: BMI000
Month 12: Body Height000
Month 12: Weight000
Month 12: BMI000
SecondaryChange From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12

Lean and fat body mass was evaluated using whole body DXA (including the head).

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · grams
Change From Baseline in Lean and Fat Body Mass From Whole Body at Months 6 and 12
gramsSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 6: Lean519.152 (13.020 to 1025.284)-410.664 (-903.724 to 82.395)168.206 (-306.981 to 643.393)
Month 12: Lean867.668 (204.535 to 1530.801)-225.474 (-901.083 to 450.136)184.164 (-448.625 to 816.953)
Month 6: Fat42.567 (-771.815 to 856.949)105.420 (-676.720 to 887.561)426.388 (-326.298 to 1179.074)
Month 12: Fat421.266 (-629.870 to 1472.401)-85.495 (-1136.234 to 965.245)792.485 (-191.238 to 1776.208)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.045 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.101 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.482 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.011 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.508 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.563 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.917 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.789 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.262 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.426 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.871 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.113 (Analysis is based on a log transformed ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12
Time frame:
Baseline, Months 1, 3, 6, 9, 12 (EOT)
Reported as:
Least squares mean · µg/L
Change From Baseline in Amino-Terminal Propeptide of Type 1 Procollagen (P1NP) up to Month 12
µg/LSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 124.349 (18.604 to 30.095)14.288 (8.221 to 20.354)0.060 (-5.827 to 5.948)
Month 317.903 (11.412 to 24.395)6.735 (0.015 to 13.455)0.640 (-6.389 to 7.670)
Month 613.096 (5.468 to 20.725)6.665 (-0.788 to 14.118)-0.429 (-8.116 to 7.258)
Month 97.265 (-0.115 to 14.644)0.238 (-7.353 to 7.830)-2.254 (-9.820 to 5.312)
Month 125.452 (-3.362 to 14.267)4.172 (-5.529 to 13.874)4.428 (-5.689 to 14.545)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.984 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.050 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.857 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.079 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.912 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.054 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.950 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.555 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.221 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.393 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.385 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12
Time frame:
Baseline, Months 1, 3, 6, 9, 12 (EOT)
Reported as:
Least squares mean · µg/L
Change From Baseline in Carboxy-Terminal Telo-Peptide [CTX-1] up to Month 12
µg/LSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 1-0.077 (-0.100 to -0.054)-0.047 (-0.071 to -0.022)-0.041 (-0.064 to -0.017)
Month 3-0.044 (-0.071 to -0.016)-0.029 (-0.058 to 0.000)-0.043 (-0.073 to -0.013)
Month 6-0.013 (-0.055 to 0.028)-0.025 (-0.065 to 0.016)-0.028 (-0.069 to 0.014)
Month 9-0.020 (-0.067 to 0.026)-0.039 (-0.087 to 0.009)-0.031 (-0.079 to 0.017)
Month 12-0.037 (-0.083 to 0.010)-0.002 (-0.053 to 0.049)-0.034 (-0.087 to 0.019)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = < 0.001 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.003 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.050 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.006 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.519 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.226 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.190 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.388 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.109 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.204 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.119 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.925 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.204 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12

The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Physical Component Summary ranges from 0 to 100, where higher scores reflect better physical functioning.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in Short Form 12 Health Survey (SF-12) Physical Component Summary Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 60.672 (-1.788 to 3.132)-0.463 (-2.821 to 1.895)1.342 (-1.129 to 3.814)
Month 12-1.178 (-3.698 to 1.341)-0.994 (-3.488 to 1.501)2.171 (-0.352 to 4.695)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.588 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.697 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.283 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.354 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.430 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.091 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12

The SF-12 is a generic, 12-item survey that measures 8 domains of health: physical functioning, role limitations due to physical health, bodily pain, general health perceptions, vitality, social functioning, role limitations due to emotional problems, and mental health. It yields scale scores for each of these 8 domains and 2 summary measures of physical and mental health: The Physical Component Summary and the Mental Component Summary. The total score for the Mental Component Summary ranges from 0 to 100, where higher scores reflect better mental health functioning.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in SF-12 Mental Component Summary Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 60.966 (-2.064 to 3.996)-0.492 (-3.411 to 2.427)-1.133 (-4.202 to 1.936)
Month 122.807 (-0.216 to 5.831)-1.473 (-4.457 to 1.511)-1.664 (-4.694 to 1.366)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.527 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.738 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.465 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.068 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.328 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.277 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12

The EQ-5D-5L is a standardised measure of health status comprised of a descriptive system of 5 health-related quality of life states (i.e., mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) and a Visual Analogue Scale (VAS) of overall health. Each dimension is rated on a 5-point response scale indicating severity of problems, where 1 is "no problems" and 5 is "extreme problems". The 5 questions are scored and together contribute to the EQ-5D index (utility) score between 0 and 1 (1 being perfect health).

Time frame:
Baseline, Months 6 and 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in Index (Utility) Score on EuroQol 5-Dimension 5-Level Descriptive System (EQ-5D-5L) Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 60.0627 (-0.0105 to 0.1359)0.0362 (-0.0343 to 0.1067)-0.0383 (-0.1121 to 0.0354)
Month 120.0424 (-0.0163 to 0.1012)0.0252 (-0.0332 to 0.0837)0.0214 (-0.0365 to 0.0793)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.092 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.310 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.304 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.155 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.392 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.464 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The total score is calculated on a 0-100 scale, where higher scores indicate a greater (negative) impact on quality of life.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in Osteogenesis Imperfecta Specific Quality of Life Questionnaire for Adults (OIQoL-A) Total Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 6-3.584 (-8.491 to 1.324)-1.848 (-6.899 to 3.203)-0.649 (-5.751 to 4.452)
Month 12-1.668 (-7.395 to 4.059)-0.587 (-6.310 to 5.137)-3.846 (-9.592 to 1.901)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.150 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.468 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.800 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.563 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.839 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.186 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Pain subscale ranges from 0 to 10, with higher value representing worse pain.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in OIQoL-A Pain Subscale Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 6-3.990 (-11.267 to 3.287)-3.906 (-11.239 to 3.426)-6.003 (-13.495 to 1.489)
Month 12-3.655 (-11.505 to 4.195)-4.968 (-12.709 to 2.772)-7.178 (-15.183 to 0.827)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.278 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.292 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.115 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.356 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.205 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.078 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryChange From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12

The OIQoL-A measures 5 areas of quality of life related to OI (Physical Function, Pain, Hearing Loss, Taking Care/Concerns, Social and Family Life and Activities). The Activities subscale ranges from 0 to 100, with higher value representing increased difficulty.

Time frame:
Baseline, Months 6, 12 (EOT)
Reported as:
Least squares mean · score on a scale
Change From Baseline in OIQoL-A Activity Subscale Score at Months 6 and 12
score on a scaleSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)
Month 6-5.980 (-11.597 to -0.363)-2.722 (-8.397 to 2.953)1.907 (-3.906 to 7.719)
Month 12-0.964 (-8.006 to 6.079)4.489 (-2.620 to 11.598)-1.630 (-8.869 to 5.609)
Statistical analysis
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.037 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.342 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.515 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 20 mg/kg (Blinded) · ANCOVA · p = 0.786 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 8 mg/kg (Blinded) · ANCOVA · p = 0.212 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
  • Setrusumab 2 mg/kg (Blinded) · ANCOVA · p = 0.655 (Analysis is based on an ANCOVA model with Change from Baseline as outcome parameter; including categorical effects of treatment and randomization stratum as well as the associated baseline value as a covariate.)
SecondaryPercentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14

Serum samples were screened for antibodies binding to setrusumab using a validated assay method by or under the supervision of the sponsor.

Time frame:
up to Month 14
Reported as:
Number · percentage of participants
Percentage of Participants Who Were Positive for Anti-Setrusumab Antibodies at Any Time During the Study up to Month 14
percentage of participantsSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)Placebo
Binding Antibodies16.117.216.79.515.0
Neutralizing Antibodies16.117.216.700
Both Binding and Neutralizing Antibodies16.117.216.700
SecondaryPercentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death

An AE is any untoward medical occurrence, which does not necessarily have a causal relationship with treatment. A serious AE (SAE) is defined as any untoward medical occurrence that, at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent disability/incapacity; is a congenital anomaly/birth defect; is another important medical event. The intensity for each AE was graded as mild, moderate or severe, according to the investigator's judgement. An event was considered related to study drug if there were a "reasonable possibility" of a relationship, according to the investigator's clinical judgment. A TEAE was defined as an event occurring or worsening on or after the first dose of study medication.

Time frame:
Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.)
Reported as:
Number · percentage of participants
Percentage of Participants With Adverse Events (AEs), Treatment-Emergent AEs (TEAEs), Serious TEAEs, and TEAEs Leading to Discontinuation or Death
percentage of participantsSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)Placebo
All AEs100.096.690.0100.090.0
TEAEs100.096.690.095.280.0
Treatment-Related TEAEs71.041.436.742.925.0
Serious TEAEs12.924.123.323.810.0
Treatment-Related Serious TEAEs6.5009.50
TEAEs Leading to Death00000
TEAEs Leading to Permanent Study Treatment Discontinuation6.5009.55.0

Adverse events

Collected over Non-serious AEs: up to Month 14; Serious AEs: up to Month 24. (Average duration of exposure to placebo was 5 months and for setrusumab was 11 month plus follow-up to 24 months.). Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Setrusumab 20 mg/kg (Blinded)0/31 (0%)4/31 (12.9%)29/31 (93.5%)
Setrusumab 8 mg/kg (Blinded)0/29 (0%)7/29 (24.1%)28/29 (96.6%)
Setrusumab 2 mg/kg (Blinded)0/30 (0%)7/30 (23.3%)27/30 (90%)
Setrusumab 20 mg/kg (Open-Label)0/21 (0%)5/21 (23.8%)19/21 (90.5%)
Placebo0/20 (0%)2/20 (10%)16/20 (80%)
Most frequent serious events
Showing 10 of 41
Most frequent serious events
EventSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)Placebo
Scapula fractureInjury, poisoning and procedural complications0/310/290/300/211/20
Pyelonephritis acuteInfections and infestations0/310/290/300/211/20
Tibia fractureInjury, poisoning and procedural complications0/311/290/301/210/20
Fibula fractureInjury, poisoning and procedural complications0/310/290/301/210/20
Lumbar vertebral fractureInjury, poisoning and procedural complications0/310/290/301/210/20
Device related infectionInfections and infestations0/310/290/301/210/20
Joint abscessInfections and infestations0/310/290/301/210/20
Pulmonary hypertensionRespiratory, thoracic and mediastinal disorders0/310/290/301/210/20
HeadacheNervous system disorders1/310/290/301/210/20
Visual impairmentEye disorders0/310/290/301/210/20
Most frequent other events
Showing 10 of 85
Most frequent other events
EventSetrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)Placebo
ArthralgiaMusculoskeletal and connective tissue disorders15/318/299/308/215/20
HeadacheNervous system disorders4/315/296/307/212/20
Foot fractureInjury, poisoning and procedural complications3/314/293/306/211/20
Back painMusculoskeletal and connective tissue disorders6/314/298/304/211/20
NasopharyngitisInfections and infestations5/313/294/305/213/20
FatigueGeneral disorders3/312/297/303/210/20
Tooth fractureInjury, poisoning and procedural complications3/312/296/300/210/20
FallInjury, poisoning and procedural complications6/314/293/302/212/20
InfluenzaInfections and infestations2/310/290/304/211/20
Pain in extremityMusculoskeletal and connective tissue disorders5/315/293/304/211/20

Baseline characteristics

The 19 participants who transitioned from the Placebo arm to the Setrusumab 20 mg/kg Open-Label arm are NOT "double-counted" for this analysis.

Age, Continuous
Age, Continuous(years)Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)PlaceboTotal
Mean40.6 ± 13.7340.4 ± 14.3447.2 ± 12.4243.5 ± 14.8540.9 ± 14.6842.4 ± 13.80
Sex: Female, Male
Sex: Female, Male(Participants)Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)PlaceboTotal
Female17202111473
Male14991639
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)PlaceboTotal
Hispanic or Latino312017
Not Hispanic or Latino272728219103
Unknown or Not Reported110002
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Setrusumab 20 mg/kg (Blinded)Setrusumab 8 mg/kg (Blinded)Setrusumab 2 mg/kg (Blinded)Setrusumab 20 mg/kg (Open-Label)PlaceboTotal
Black or African American211004
White292729220107
Not Collected or Not Reported010001
07

Study locations

25 sites
  • Mereo Investigator Site
    Birmingham, Alabama 35294, United States
  • Mereo Investigator Site
    Jacksonville, Florida 32207, United States
  • Mereo Investigator Site
    Baltimore, Maryland 21287, United States
  • Mereo Investigator Site
    Boston, Massachusetts 012115, United States
  • Mereo Investigator Site
    Saint Paul, Minnesota 55101, United States
  • Mereo Investigator Site
    Saint Louis, Missouri 63110, United States
  • Mereo Investigator Site
    Albuquerque, New Mexico 87106, United States
  • Mereo Investigator Site
    Cincinnati, Ohio 45229, United States
  • Mereo Investigator Site
    Portland, Oregon 97239, United States
  • Mereo Investigator Site
    Pittsburgh, Pennsylvania 15225, United States
  • Mereo Investigator Site
    Nashville, Tennessee 37232, United States
  • Mereo Investigator Site
    Houston, Texas 77030, United States
  • Mereo Investigator Site
    Toronto, Ontario, Canada
  • Mereo Investigator Site
    Montreal, Quebec, Canada
  • Mereo Investigator Site
    Quebec City, Quebec, Canada
  • Mereo Investigator Site
    Aarhus, Denmark
  • Mereo Investigator Site
    Odense, Denmark
  • Mereo Investigator Site
    Paris, Paris Cedex 14, France
  • Mereo Investigator Site
    Lyon, France
  • Mereo Investigator Site
    Paris, France
  • Mereo Investigator Site
    Cambridge, Cambridgeshire, United Kingdom
  • Mereo Investigator Site
    Newcastle upon Tyne, Newcastle, United Kingdom
  • Mereo Investigator Site
    Oxford, Oxfordshire, United Kingdom
  • Mereo Investigator Site
    Bristol, United Kingdom
  • Mereo Investigator Site
    London, United Kingdom
08

References and documents

Study documents

  • Study protocol · Jul 19, 2019
  • Statistical analysis plan · Oct 22, 2019

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

09

Registry details

Key details

Study ID
NCT03118570
Lead sponsor
Ultragenyx Pharmaceutical Inc
Collaborators
Mereo BioPharma
Responsible party
Sponsor
First posted
Apr 18, 2017
Start date
Sep 11, 2017
Primary completion
Oct 1, 2019
Completion
Nov 12, 2020
Results posted
Mar 2, 2022
Last update
Jul 5, 2023

Study contacts

Medical Director
study director · Mereo BioPharma

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
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