CClinicalTrials.gg
Sign In
CompletedNCT04545554Updated Apr 15, 2024Results posted

Study to Evaluate Romosozumab in Children and Adolescents With Osteogenesis Imperfecta

A Phase 1 interventional study of Romosozumab and Calcium in Osteogenesis Imperfecta, sponsored by Amgen. Completed at 15 sites in 8 countries. Open to participants aged 5 Years to 17 Years. Per ClinicalTrials.gov, last updated 2024-04-15.

Sponsored by Amgen · Phase 1, Interventional, and Treatment

Phase
Phase 1
Study type
Interventional
Enrollment
25
Allocation
Non-randomized
Ages
5 Years to 17 Years
Sex
All
01

Study summary

The primary objective of this study is to evaluate the pharmacokinetics (PK) profile following multiple subcutaneous (SC) doses of romosozumab in children and adolescents with Osteogenesis Imperfecta (OI).

02

Conditions studied

  • Osteogenesis Imperfecta
03

Who can participate

Ages eligible
5 Years to 17 Years
Sexes eligible
All
Accepts healthy volunteers
No

Inclusion criteria

  • Ambulatory male or female children 5 to less than 18 years of age upon entry into screening
  • Clinical diagnosis of OI defined as a clinical history consistent with type I-IV OI as determined by presence of expected phenotype and lack of additional features unrelated to type I-IV OI

Exclusion criteria

Exclusion Criteria

  • History of an electrophoresis pattern inconsistent with type I to type IV OI
  • History of known mutation in a gene other than collagen type I alpha 1/collagen type I alpha 2 (COL1AI/COL1A2) causing OI or other metabolic bone disease
  • History of other bone diseases that affect bone metabolism (eg, osteoporosis pseudoglioma syndrome, idiopathic juvenile osteoporosis, osteopetrosis, hypophosphatasia)
  • History of Kawasaki disease, rheumatic myocarditis, ischemic cardiomyopathy, inherited cardiomyopathies, nephrotic syndrome, familial hypercholesterolemia, stroke, or any thromboembolic disorder
  • Unhealed fracture as defined by orthopedic opinion
  • Symptoms associated with skull abnormalities such as basilar invagination, basilar impression or Chiari malformation
  • Prior treatment with anti-sclerostin antibody, fluoride or strontium, parathyroid hormone (PTH) within 12 months prior to screening, denosumab within 12 months or zoledronic acid within 6 months prior to first dose
  • Less than 2 evaluable vertebrae by DXA evaluation in the region of interest, L1 - L4, as confirmed by the central imaging laboratory.
  • Clinically significant valvular heart disease based on local echocardiogram (ECHO) results.
04

Study design

Phase
Phase 1
Primary purpose
Treatment
Allocation
Non-randomized
Intervention model
Sequential assignment
Masking
None (open label)
Enrollment
25 participants (actual)

Study arms

  • Experimental
    Romosozumab: 12 - < 18 Years of Age

    Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.

    Drug: Romosozumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D

  • Experimental
    Romosozumab: 5 - < 12 Years of Age

    Participants will receive 1 of 3 dose levels of romosozumab. All participants also received calcium and vitamin D.

    Drug: Romosozumab · Dietary Supplement: Calcium · Dietary Supplement: Vitamin D

Interventions

  • DrugRomosozumab

    Participants will receive multiple doses of romosozumab via a SC injection.

  • Dietary supplementCalcium

    All participants will receive daily supplements of elemental calcium.

  • Dietary supplementVitamin D

    All participants will receive daily supplementation with vitamin D.

05

What researchers measure

Primary outcomes

  1. Maximum Observed Serum Concentration (Cmax) of Romosozumab

    Mean Cmax values following Days 1 and 57 are presented.

    Time frame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57

  2. Time to Cmax (Tmax) of Romosozumab

    Median tmax values following Days 1 and 57 are presented.

    Time frame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57

  3. Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab

    Mean AUC(0-28) values following Days 1 and 57 are presented.

    Time frame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57

  4. Accumulation Ratio of Romosozumab

    The accumulation ratio was calculated as AUC(0-28) at Day 57/AUC(0-28) at Day 1. Mean accumulation ratio values based on analysis at Days 1 and 57 are presented, as pre-specified.

    Time frame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57

  5. Terminal Half-life of Romosozumab

    Median terminal half-life values at Day 57 are presented.

    Time frame: Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Day 57

Secondary outcomes

  1. Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

    TEAEs were adverse events (AEs) that started on or after first dose of investigational product up to the end of study (up to Day 169). Any clinically significant changes in vital signs, electrocardiogram parameters, physical exam findings, and clinical laboratory parameters were reported as TEAEs. Injection site reactions were events of interest (EOI) for this study.

    Time frame: Day 1 to end of study (up to Day 169); median duration on study was 5.55 months

  2. Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

    Facial nerve (cranial nerve VII) function was assessed clinically by facial symmetry inspection at rest, followed by assessment of the symmetry of specific facial movements: raising eyebrows, closing the eyes, blowing out the cheeks, smiling, pursing and closing the lips. Results of the cranial nerve examination were classed as 0 = Normal; 1 = Abnormal not clinically significant; and 2 = Abnormal clinically significant. An increase from baseline indicates an increase in abnormal clinical findings on the cranial nerve VII examination.

    Time frame: Baseline (Day 1), Day 57, Day 85, and Day 169

  3. Number of Participants With Anti-romosozumab Antibodies

    Treatment-boosted anti-romosozumab antibody was defined as binding antibody positive at baseline with a \>4 x increase in magnitude post-baseline. Transient results were defined as negative results at the participant's last time point tested within the study period.

    Time frame: Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169

  4. Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

    Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points.

    Time frame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169

  5. Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

    Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points.

    Time frame: Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169

  6. Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

    BMD was assessed by dual energy X-ray absorptiometry (DXA) scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

    Time frame: DXA scans were during screening (baseline) and at Day 85 and Day 169

  7. Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

    BMC was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

    Time frame: DXA scans were during screening (baseline) and at Day 85 and Day 169

  8. Percentage Change From Baseline in Lumbar Spine Bone Area

    Bone area was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

    Time frame: DXA scans were during screening (baseline) and at Day 85 and Day 169

  9. Mean Change From Baseline in Lumbar Spine BMD Z-Score

    Lumbar spine BMD was assessed by DXA scans. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from baseline indicated an improvement in lumbar spine BMD.

    Time frame: DXA scans were during screening (baseline) and at Day 85 and Day 169

06

Results

Posted Apr 15, 2024

Participant flow

Participants were enrolled at 15 study centers in Austria, Germany, Greece, Hungary, Italy, Spain, Turkey, and the United States, and participated from 21 January 2021 until 30 March 2023.

Participant flow — Overall Study
MilestoneCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Started444544
Received at least 1 dose romosozumab444544
Received all doses of romosozumab444444
Completed444444
Not completed000100
Withdrew: Withdrawal by subject000100

Outcome measures

PrimaryMaximum Observed Serum Concentration (Cmax) of Romosozumab

Mean Cmax values following Days 1 and 57 are presented.

Time frame:
Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
Reported as:
Mean · μg/mL
Maximum Observed Serum Concentration (Cmax) of Romosozumab
μg/mLCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 12.64 ± 1.061.74 ± 0.82513.8 ± 6.3210.3 ± 1.7025.7 ± 3.0221.3 ± 6.45
Day 572.43 ± 1.365.55 ± 2.1112.8 ± 6.319.14 ± 7.5022.8 ± 10.519.4 ± 2.14
PrimaryTime to Cmax (Tmax) of Romosozumab

Median tmax values following Days 1 and 57 are presented.

Time frame:
Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Days 1 and 57
Reported as:
Median · day
Time to Cmax (Tmax) of Romosozumab
dayCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 16.5 (5.9 to 7.9)7.9 (7.9 to 15)6.9 (6.9 to 7.0)6.9 (4.9 to 7.1)7.0 (4.9 to 8.0)7.5 (6.9 to 8.9)
Day 577.0 (7.0 to 12)7.0 (6.9 to 7.0)7.0 (6.0 to 7.9)8.0 (6.0 to 11)7.0 (4.0 to 12)7.5 (6.0 to 8.8)
PrimaryArea Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab

Mean AUC(0-28) values following Days 1 and 57 are presented.

Time frame:
Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
Reported as:
Mean · day*μg/mL
Area Under the Serum Concentration Time Curve (AUC) From Time 0 to Day 28 (AUC[0-28]) of Romosozumab
day*μg/mLCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 130.9 ± 13.516.9 ± 5.78163 ± 89.1113 ± 50.3344 ± 106234 ± 93.7
Day 5727.4 ± 15.150.5 ± 20.7153 ± 86.795.1 ± 76.1293 ± 134203 ± 40.7
PrimaryAccumulation Ratio of Romosozumab

The accumulation ratio was calculated as AUC(0-28) at Day 57/AUC(0-28) at Day 1. Mean accumulation ratio values based on analysis at Days 1 and 57 are presented, as pre-specified.

Time frame:
Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, and 85; pre-specified PK analysis took place on Days 1 and 57
Reported as:
Mean · ratio
Accumulation Ratio of Romosozumab
ratioCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Accumulation Ratio of Romosozumab0.885 ± 0.4873.6 ± 2.560.922 ± 0.06730.724 ± 0.3920.843 ± 0.2600.935 ± 0.283
PrimaryTerminal Half-life of Romosozumab

Median terminal half-life values at Day 57 are presented.

Time frame:
Single blood samples were taken on days 1, 8, 15, 29, 57, 64, 71, 85, 113, and 169 (end of study); pre-specified PK analysis took place on Day 57
Reported as:
Median · day
Terminal Half-life of Romosozumab
dayCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Terminal Half-life of Romosozumab—9.41 (7.62 to 11.2)—7.01 (7.01 to 7.01)6.11 (5.58 to 6.56)—
SecondaryNumber of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs were adverse events (AEs) that started on or after first dose of investigational product up to the end of study (up to Day 169). Any clinically significant changes in vital signs, electrocardiogram parameters, physical exam findings, and clinical laboratory parameters were reported as TEAEs. Injection site reactions were events of interest (EOI) for this study.

Time frame:
Day 1 to end of study (up to Day 169); median duration on study was 5.55 months
Reported as:
Count of participants · Participants
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
ParticipantsCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Any TEAE112413
Any Treatment-emergent EOI000011
SecondaryNumber of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169

Facial nerve (cranial nerve VII) function was assessed clinically by facial symmetry inspection at rest, followed by assessment of the symmetry of specific facial movements: raising eyebrows, closing the eyes, blowing out the cheeks, smiling, pursing and closing the lips. Results of the cranial nerve examination were classed as 0 = Normal; 1 = Abnormal not clinically significant; and 2 = Abnormal clinically significant. An increase from baseline indicates an increase in abnormal clinical findings on the cranial nerve VII examination.

Time frame:
Baseline (Day 1), Day 57, Day 85, and Day 169
Reported as:
Count of participants · Participants
Number of Participants With Changes From Baseline in Cranial Nerve VII Examination Findings at Day 57, Day 85, and Day 169
ParticipantsCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 57: Blowing out of cheeks - No change (0)444344
Day 57: Blowing out of cheeks - Undetermined000200
Day 57: Closing eyes - No change (0)444344
Day 57: Closing eyes - Undetermined000200
Day 57: Closing of lips - No change (0)444344
Day 57: Closing of lips - Undetermined000200
Day 57: Pursing of lips - No change (0)444344
Day 57: Pursing of lips - Undetermined000200
Day 57: Raising eyebrows - No change (0)444344
Day 57: Raising eyebrows - Undetermined000200
Day 57: Smiling - No change (0)444344
Day 57: Smiling - Undetermined000200
Day 85: Blowing out of cheeks - No change (0)444444
Day 85: Blowing out of cheeks - Undetermined000100
Day 85: Closing eyes - No change (0)444444
Day 85: Closing eyes - Undetermined000100
Day 85: Closing of lips - No change (0)434444
Day 85: Closing of lips - Increase (to 1)010000
Day 85: Closing of lips - Undetermined000100
Day 85: Pursing of lips - No change (0)444444
Day 85: Pursing of lips - Undetermined000100
Day 85: Raising eyebrows - No change (0)444444
Day 85: Raising eyebrows - Undetermined000100
Day 85: Smiling - No change (0)444444
Day 85: Smiling - Undetermined000100
Day 169: Blowing out of cheeks - No change (0)444444
Day 169: Blowing out of cheeks - Undetermined000100
Day 169: Closing eyes - No change (0)444444
Day 169: Closing eyes - Undetermined000100
Day 169: Closing of lips - No change (0)444444
Day 169: Closing of lips - Undetermined000100
Day 169: Pursing of lips - No change (0)444444
Day 169: Pursing of lips - Undetermined000100
Day 169: Raising eyebrows - No change (0)444444
Day 169: Raising eyebrows - Undetermined000100
Day 169: Smiling - No change (0)444444
Day 169: Smiling - Undetermined000100
SecondaryNumber of Participants With Anti-romosozumab Antibodies

Treatment-boosted anti-romosozumab antibody was defined as binding antibody positive at baseline with a \>4 x increase in magnitude post-baseline. Transient results were defined as negative results at the participant's last time point tested within the study period.

Time frame:
Blood samples for anti-romosozumab antibodies were taken Day 1, Day 15, Day 29, Day 85, and Day 169
Reported as:
Count of participants · Participants
Number of Participants With Anti-romosozumab Antibodies
ParticipantsCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Binding antibody positive anytime012011
Neutralizing antibody positive anytime002010
Binding antibody positive at/before baseline000000
Neutralizing antibody positive at/before baseline000000
Treatment-boosted antibody positive000000
Binding antibody positive post-baseline with negative/no results at baseline012011
Transient binding antibody positive post-baseline with negative/no results at baseline000000
Neutralizing antibody positive post-baseline with a negative/no result at baseline002010
Transient neutralizing antibody positive post-baseline with a negative/no result at baseline000000
SecondaryPercentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)

Serum concentrations of the bone turnover marker CTX were determined at pre-specified time points.

Time frame:
Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Reported as:
Mean · percentage change
Percentage Change From Baseline in Serum Concentrations of Serum Type 1 Collagen C-Telopeptide (CTX)
percentage changeCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 82.65 ± 27.91-19.93 ± 33.978.79 ± 19.21-19.38 ± 20.01-12.33 ± 12.937.14 ± 29.89
Day 1512.26 ± 28.20-3.24 ± 41.30-2.14 ± 52.91-20.24 ± 21.12-17.22 ± 17.3942.62 ± 54.95
Day 29-4.67 ± 21.35-6.67 ± 39.9926.00 ± 15.11-7.43 ± 18.63-16.09 ± 27.053.76 ± 24.72
Day 571.03 ± 34.14-7.34 ± 25.32-0.32 ± 32.21-7.66 ± 13.16-1.40 ± 38.1044.17 ± 95.30
Day 64-13.37 ± 36.33-18.26 ± 49.1919.91 ± 43.95-10.60 ± 36.1210.95 ± 23.38-28.14 ± 11.51
Day 7118.20 ± 53.85-25.30 ± 50.4335.26 ± 68.16-3.37 ± 8.2515.14 ± 51.3960.12 ± 106.28
Day 85-10.56 ± 22.18-37.50 ± 14.129.95 ± 30.715.08 ± 24.340.71 ± 44.5515.77 ± 58.40
Day 113-3.83 ± 22.30-30.38 ± 19.5925.94 ± 39.766.98 ± 37.987.03 ± 40.23-19.58 ± 10.98
Day 169-6.15 ± 54.87-29.78 ± 31.60-1.72 ± 40.4211.08 ± 16.19-8.07 ± 16.738.08 ± 49.45
SecondaryPercentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)

Serum concentrations of the bone turnover marker P1NP were determined at pre-specified time points.

Time frame:
Blood samples were taken Days 1 (baseline), 8, 15, 29, 57, 64, 71, 85, 113, and 169
Reported as:
Mean · percentage change
Percentage Change From Baseline in Serum Concentrations of Procollagen Type 1 N-terminal Propeptide (P1NP)
percentage changeCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 819.81 ± 20.9612.75 ± 13.0365.12 ± 17.7531.77 ± 11.6935.91 ± 21.8935.35 ± 47.08
Day 1511.03 ± 13.9412.43 ± 13.0752.25 ± 29.7110.52 ± 14.7258.58 ± 54.6128.35 ± 55.00
Day 295.24 ± 12.876.18 ± 18.6421.52 ± 25.011.96 ± 9.2232.13 ± 59.10-11.54 ± 11.35
Day 57-2.11 ± 20.26-22.37 ± 19.8214.57 ± 36.09-6.36 ± 17.5119.07 ± 56.24-14.26 ± 12.93
Day 6414.82 ± 28.8619.12 ± 40.4839.63 ± 31.9225.42 ± 16.7377.17 ± 109.0717.51 ± 35.74
Day 7112.19 ± 21.37-5.72 ± 28.5049.37 ± 37.9916.79 ± 12.2942.16 ± 59.395.12 ± 29.54
Day 85-7.34 ± 22.50-23.50 ± 13.4226.12 ± 48.97-0.72 ± 21.295.79 ± 23.45-11.78 ± 30.09
Day 113-1.13 ± 13.42-13.75 ± 19.1121.10 ± 40.612.53 ± 42.46-5.02 ± 21.00-26.95 ± 10.23
Day 169-6.62 ± 30.96-3.13 ± 10.5418.10 ± 57.53-2.24 ± 23.99-14.30 ± 19.41-21.85 ± 16.18
SecondaryPercentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine

BMD was assessed by dual energy X-ray absorptiometry (DXA) scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

Time frame:
DXA scans were during screening (baseline) and at Day 85 and Day 169
Reported as:
Mean · percentage change
Percentage Change From Baseline in Bone Mineral Density (BMD) of the Lumbar Spine
percentage changeCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 854.84 ± 3.297.94 ± 5.3212.91 ± 2.607.78 ± 9.167.88 ± 1.9913.07 ± 13.45
Day 1697.80 ± 2.239.24 ± 7.9815.04 ± 4.327.09 ± 7.037.10 ± 6.5812.70 ± 12.86
SecondaryPercentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine

BMC was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

Time frame:
DXA scans were during screening (baseline) and at Day 85 and Day 169
Reported as:
Mean · percentage change
Percentage Change From Baseline in Bone Mineral Content (BMC) of the Lumbar Spine
percentage changeCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 857.68 ± 8.1010.13 ± 6.0518.16 ± 7.868.41 ± 6.9014.62 ± 3.3916.03 ± 8.32
Day 16912.64 ± 4.0711.40 ± 7.8221.29 ± 11.317.98 ± 7.7714.27 ± 5.5212.42 ± 10.72
SecondaryPercentage Change From Baseline in Lumbar Spine Bone Area

Bone area was assessed by DXA scans of the anteroposterior lumbar spine (L1 through L4) and analyzed by a central imaging laboratory. At least 2 lumbar vertebrae from L1 - L4 must be evaluable by DXA.

Time frame:
DXA scans were during screening (baseline) and at Day 85 and Day 169
Reported as:
Mean · percentage change
Percentage Change From Baseline in Lumbar Spine Bone Area
percentage changeCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 852.72 ± 6.992.03 ± 1.624.60 ± 5.000.80 ± 4.626.23 ± 2.153.44 ± 11.05
Day 1694.53 ± 4.921.92 ± 0.665.30 ± 6.060.82 ± 1.956.87 ± 5.14-0.09 ± 4.27
SecondaryMean Change From Baseline in Lumbar Spine BMD Z-Score

Lumbar spine BMD was assessed by DXA scans. The results were then converted to Z-scores. The Z-score indicated the number of standard deviations away from the reference population and a score of 0 is equal to the mean. Positive changes from baseline indicated an improvement in lumbar spine BMD.

Time frame:
DXA scans were during screening (baseline) and at Day 85 and Day 169
Reported as:
Mean · Z-score
Mean Change From Baseline in Lumbar Spine BMD Z-Score
Z-scoreCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Day 850.20 ± 0.390.45 ± 0.370.50 ± 0.120.33 ± 0.530.33 ± 0.260.53 ± 0.79
Day 1690.33 ± 0.460.48 ± 0.510.48 ± 0.210.25 ± 0.390.23 ± 0.560.50 ± 0.62

Adverse events

Collected over All-cause mortality was collected from enrollment to the end of study visit (Day 169); median time on study was 5.55 months. Adverse events were collected from first dose of study drug until the end of study visit (Day 169); median duration was 5.55 months.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)0/4 (0%)0/4 (0%)1/4 (25%)
Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)0/4 (0%)1/4 (25%)0/4 (0%)
Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)0/4 (0%)0/4 (0%)2/4 (50%)
Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)0/5 (0%)1/5 (20%)4/5 (80%)
Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)0/4 (0%)0/4 (0%)1/4 (25%)
Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)0/4 (0%)0/4 (0%)3/4 (75%)
Most frequent serious events
Most frequent serious events
EventCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Lower limb fractureInjury, poisoning and procedural complications0/41/40/40/50/40/4
Femur fractureInjury, poisoning and procedural complications0/40/40/41/50/40/4
Most frequent other events
Showing 10 of 34
Most frequent other events
EventCohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)
Upper respiratory tract infectionInfections and infestations0/40/40/40/50/42/4
Pain in extremityMusculoskeletal and connective tissue disorders0/40/40/41/50/42/4
HeadacheNervous system disorders0/40/40/40/50/42/4
CoughRespiratory, thoracic and mediastinal disorders0/40/40/40/50/42/4
Abdominal painGastrointestinal disorders0/40/40/40/50/41/4
DiarrhoeaGastrointestinal disorders1/40/40/40/50/40/4
ToothacheGastrointestinal disorders0/40/40/40/51/40/4
Injection site erythemaGeneral disorders0/40/40/40/51/41/4
Injection site painGeneral disorders0/40/40/40/50/41/4
Injection site swellingGeneral disorders0/40/40/40/51/41/4

Baseline characteristics

Age, Continuous
Age, Continuous(years)Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)Total
Mean14.3 ± 1.96.0 ± 1.414.3 ± 0.58.4 ± 2.414.0 ± 1.86.5 ± 0.610.5 ± 4.0
Sex: Female, Male
Sex: Female, Male(Participants)Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)Total
Female1014219
Male34312316
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)Total
Hispanic or Latino0002103
Not Hispanic or Latino44433422
Unknown or Not Reported0000000
Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)Cohort 1: Romosozumab Dose A (12 to < 18 Years of Age)Cohort 2: Romosozumab Dose A (5 to < 12 Years of Age)Cohort 3: Romosozumab Dose B (12 to < 18 Years of Age)Cohort 4: Romosozumab Dose B (5 to < 12 Years of Age)Cohort 5: Romosozumab Dose C (12 to < 18 Years of Age)Cohort 6: Romosozumab Dose C (5 to < 12 Years of Age)Total
Asian0000011
White44444222
Other0001012
07

Study locations

15 sites
  • Riley Hospital for Children
    Indianapolis, Indiana 46202, United States
  • Vanderbilt University Medical Center
    Nashville, Tennessee 37212-3157, United States
  • The Medical College of Wisconsin
    Milwaukee, Wisconsin 53226, United States
  • Kepler Universitaetsklinikum GmbH
    Linz, 4020, Austria
  • Uniklinik Köln
    Koeln, 50937, Germany
  • General Children Hospital Panagioti and Aglaias Kyriakou
    Athens, 11527, Greece
  • Semmelweis Egyetem
    Budapest, 1094, Hungary
  • IRCCS Ospedale Pediatrico Bambino Gesu
    Roma, 00165, Italy
  • Hospital Sant Joan de Deu
    Esplugues de Llobregat, Cataluña 08950, Spain
  • Hospital Universitari i Politecnic La Fe
    Valencia, Comunidad Valenciana 46026, Spain
  • Hospital Universitario de Getafe
    Getafe, Madrid 28905, Spain
  • Hospital de Cruces
    Baracaldo, País Vasco 48903, Spain
  • Gazi Universitesi Tip Fakultesi
    Ankara, 06500, Turkey
  • Koc Universitesi Hastanesi
    Istanbul, 34010, Turkey
  • Ege Universitesi Ilac Gelistirme ve Farmakokinetik Arastirma Uygulama Merkezi (ARGEFAR)
    Izmir, 35100, Turkey
08

References and documents

Study documents

  • Study protocol · Feb 28, 2023
  • Statistical analysis plan · Apr 15, 2023

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

Individual participant data

Plan to share: Yes — De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting information: Study protocol, Sap, Icf, Csr

09

Registry details

Key details

Study ID
NCT04545554
Lead sponsor
Amgen
Responsible party
Sponsor
First posted
Sep 11, 2020
Start date
Jan 21, 2021
Primary completion
Mar 30, 2023
Completion
Mar 30, 2023
Results posted
Apr 15, 2024
Last update
Apr 15, 2024

Study contacts

MD
study director · Amgen

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Other studies in this condition

Osteogenesis Imperfecta→

Other studies from this sponsor

Amgen

Start the discussion