A Phase 3 interventional study of burosumab and Placebo in X-linked Hypophosphatemia, sponsored by Kyowa Kirin, Inc.. Completed at 25 sites in 7 countries. Open to participants aged 18 Years to 65 Years. Per ClinicalTrials.gov, last updated 2024-06-18.
Sponsored by Kyowa Kirin, Inc. · Phase 3, Interventional, and Treatment
The primary efficacy objective of this study is to establish the effect of burosumab treatment compared with placebo on increasing serum phosphorus levels in adults with XLH.
49 studies on the registry are indexed under Familial Hypophosphatemic Rickets; 8 are open to participants now.
This study's enrollment of 134 is above the median of 28 across 29 interventional studies indexed under Familial Hypophosphatemic Rickets.
Browse Familial Hypophosphatemic Rickets studies →Kyowa Kirin, Inc. is the lead sponsor of 36 studies on the registry; 2 are open to participants now.
Of its 7 completed or terminated interventional studies of FDA-regulated products, 3 (43%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Diagnosis of XLH supported by classic clinical features of adult XLH (such as short stature or bowed legs) and at least ONE of the following at Screening:
Biochemical findings consistent with XLH at Screening Visit 2 following overnight fasting (min. 8 hours):
Exclusion Criteria:
Use of any product or investigational medical device within 30 days prior to Screening Visit 1, or requirement for any investigational agent prior to completion of all scheduled study assessments.
OR, in Japan, use of any investigational product or investigational medical device within 4 months prior to Screening, or requirement for any investigational agent prior to completion of all scheduled study assessments.
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Childbearing potential
Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).
Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Corticosteroids (steroids)
Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.
Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Excipients
The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Burosumab 1 mg/kg administered subcutaneously (SC) every 4 weeks, for the duration of the study.
Biological: burosumab
Placebo administered SC every 4 weeks through Week 24, followed by burosumab 1 mg/kg, for the duration of the study.
Biological: burosumab · Other: Placebo
solution for SC injection
Also known as: UX023, KRN23, Crysvita
saline solution for SC injection
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score
The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). From the generalized estimating equation (GEE) model, which includes the change from Baseline for the endpoint of interest as the dependent variable; region, visit, treatment, actual randomization stratification (not included for analysis of BPI Worst Pain), and visit by treatment as fixed factors; and Baseline value for the endpoint of interest as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, 24 weeks
Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, 24 weeks
Change From Baseline to Week 24 in the WOMAC Physical Function Score
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Physical Function as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Physical Function as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, 24 weeks
Change From Baseline Over Time in BPI Worst Pain Score
Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for BPI worst pain as the dependent variable, region, visit, treatment and visit by treatment as fixed factors, and baseline of BPI Worst Pain as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in BPI Pain Severity Score
Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in BPI Pain Interference Score
Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in WOMAC Stiffness Score
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144
Change From Baseline Over Time in WOMAC Physical Function Score
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144
Change From Baseline Over Time in BFI Worst Fatigue Score
Change from baseline to post-baseline visits in Brief Fatigue Inventory Question 3 (Worst Fatigue in Past 24 Hours; BFI-Q3) as averaged from daily diary scores recorded over 1 week and the study visit score. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in BFI Global Fatigue Score
Change from baseline to post-baseline visits in BFI global fatigue score, calculated by averaging all 9 BFI items as recorded on the day of the study visit. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference. The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP)
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)
The GEE Estimates are from the GEE model which includes the change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx
The GEE Estimates are from the GEE model which includes the percent change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP)
The GEE Estimates are from the GEE model which includes the change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of BALP as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP
The GEE Estimates are from the GEE model which includes the percent change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in Serum Phosphorus
The GEE Estimates are from the GEE model which includes the change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Percent Change From Baseline Over Time in Serum Phosphorus
The GEE Estimates are from the GEE model which includes the percent change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 1, 2, 4, 6, 10, 12, 14, 18, 20, 21, 22, 24, 26, 28, 34, 36, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Change From Baseline Over Time in Serum 1,25(OH)2D
The GEE Estimates are from the GEE model which includes the change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Percent Change From Baseline Over Time in Serum 1,25(OH)2D
The GEE Estimates are from the GEE model which includes the percent change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
The GEE Estimates are from the GEE model which includes the change from baseline for 24-Hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Week 12, 24, 36, 48, 72, 96
Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus
The GEE Estimates are from the GEE model which includes the percent change from baseline for 24-hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Week 12, 24, 36, 48, 72, 96
Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR)
The GEE Estimates are from the GEE model which includes the change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Percent Change From Baseline Over Time in TmP/GFR
The GEE Estimates are from the GEE model which includes the percent change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP)
The GEE Estimates are from the GEE model which includes the change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Percent Change From Baseline Over Time in TRP
The GEE Estimates are from the GEE model which includes the percent change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Time frame: Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Percent Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline through Week 24
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
Time frame: Baseline through Week 24
| Milestone | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Started | 66 | 68 |
| Completed | 66 | 67 |
| Not completed | 0 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Milestone | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Started | 66 | 67 |
| Completed | 63 | 63 |
| Not completed | 3 | 4 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Other, not specified | 3 | 3 |
| Milestone | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Started | 63 | 63 |
| Completed | 60 | 59 |
| Not completed | 3 | 4 |
| Withdrew: Death | 0 | 1 |
| Withdrew: Other, not specified | 3 | 1 |
| Withdrew: Withdrawal by subject | 0 | 1 |
| Withdrew: Lost to follow-up | 0 | 1 |
| Milestone | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Started | 52 | 49 |
| Completed | 51 | 49 |
| Not completed | 1 | 0 |
| Withdrew: Other, not specified | 1 | 0 |
| percentage of participants | Placebo | Burosumab |
|---|---|---|
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 | 7.6 (3.3 to 16.5) | 92.6 (83.9 to 96.8) |
The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). From the generalized estimating equation (GEE) model, which includes the change from Baseline for the endpoint of interest as the dependent variable; region, visit, treatment, actual randomization stratification (not included for analysis of BPI Worst Pain), and visit by treatment as fixed factors; and Baseline value for the endpoint of interest as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab |
|---|---|---|
| Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score | -0.32 ± 0.222 | -0.79 ± 0.211 |
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab |
|---|---|---|
| Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score | 0.46 ± 3.139 | -7.85 ± 3.034 |
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Physical Function as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Physical Function as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab |
|---|---|---|
| Change From Baseline to Week 24 in the WOMAC Physical Function Score | 1.79 ± 2.722 | -3.11 ± 2.553 |
Change from baseline to post-baseline visits in BPI-Q3 (Worst Pain) score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Question 3 of the short-form BPI (BPI-Q3) asks subjects to rate their pain at its worst in the last 24 hours on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for BPI worst pain as the dependent variable, region, visit, treatment and visit by treatment as fixed factors, and baseline of BPI Worst Pain as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -0.37 ± 0.216 | -0.62 ± 0.208 |
| Change at Week 24 | -0.31 ± 0.242 | -0.77 ± 0.228 |
| Change at Week 36 | -1.25 ± 0.234 | -0.95 ± 0.228 |
| Change at Week 48 | -1.49 ± 0.243 | -1.05 ± 0.230 |
| Change at Week 72 | -1.28 ± 0.283 | -1.21 ± 0.316 |
| Change at Week 96 | -0.99 ± 0.265 | -1.48 ± 0.299 |
Change from baseline to post-baseline visits in BPI pain severity score as averaged from daily diary scores recorded over 1 week and the study visit score. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). The severity of pain in the last 24 hours is rated on a scale of 0 (no pain) to 10 (pain as bad as you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -0.32 ± 0.166 | -0.43 ± 0.163 |
| Change at Week 24 | -0.10 ± 0.211 | -0.53 ± 0.172 |
| Change at Week 36 | -0.97 ± 0.214 | -0.62 ± 0.184 |
| Change at Week 48 | -1.13 ± 0.205 | -0.79 ± 0.162 |
| Change at Week 72 | -1.36 ± 0.216 | -1.24 ± 0.231 |
| Change at Week 96 | -1.18 ± 0.195 | -1.42 ± 0.229 |
Change from baseline to post-baseline visits in BPI pain interference score as recorded on the day of the study visit. The BPI evaluates the condition of all pain over the previous 24 hours. Two dimensions are measured: pain severity (worst, least, average, and now) and the impact of pain on functioning (pain interference with general activity, walking, work, mood, enjoyment of life, relations with others, and sleep). Pain interference in the last 24 hours is rated on a scale of 0 (does not interfere) to 10 (completely interferes). The GEE Estimates are from the GEE model which includes the change from baseline for each BPI endpoint as the dependent variable, region, visit, treatment, and visit by treatment as fixed factors, and baseline of each BPI endpoint as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -0.29 ± 0.215 | -0.51 ± 0.207 |
| Change at Week 24 | -0.28 ± 0.242 | -0.41 ± 0.207 |
| Change at Week 36 | -1.30 ± 0.260 | -0.79 ± 0.221 |
| Change at Week 48 | -1.28 ± 0.251 | -1.04 ± 0.235 |
| Change at Week 72 | -1.22 ± 0.247 | -1.24 ± 0.263 |
| Change at Week 96 | -1.08 ± 0.260 | -1.43 ± 0.234 |
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -1.24 ± 2.929 | -7.86 ± 3.622 |
| Change at Week 24 | 0.20 ± 3.289 | -8.01 ± 2.968 |
| Change at Week 36 | -13.50 ± 3.422 | -12.58 ± 3.411 |
| Change at Week 48 | -15.83 ± 3.488 | -16.63 ± 3.302 |
| Change at Week 72 | -18.02 ± 3.613 | -15.47 ± 3.111 |
| Change at Week 96 | -17.67 ± 3.737 | -15.32 ± 3.577 |
| Change at Week 120 | -19.23 ± 3.404 | -20.57 ± 3.371 |
| Change at Week 144 | -30.64 ± 4.407 | -25.88 ± 4.501 |
The WOMAC is a 24-item participant-reported questionnaire with two domains, Stiffness (2 questions) and Physical Function (17 questions) over the previous 48 hours. The WOMAC is administered in a 5-point Likert-scale format using descriptors of none, mild, moderate, severe, and extreme corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse stiffness and functional limitations. Scores are normalized to a 0-100 metric where 0 was the best health state and 100 the worst. The GEE Estimates are from the GEE model which includes the change from baseline for WOMAC Stiffness as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of WOMAC Stiffness as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -1.40 ± 2.418 | -3.96 ± 1.787 |
| Change at Week 24 | 1.14 ± 2.531 | -3.45 ± 2.193 |
| Change at Week 36 | -5.47 ± 2.694 | -7.14 ± 2.133 |
| Change at Week 48 | -7.15 ± 2.801 | -8.42 ± 2.057 |
| Change at Week 72 | -8.68 ± 2.835 | -8.66 ± 2.523 |
| Change at Week 96 | -8.41 ± 2.752 | -9.02 ± 2.270 |
| Change at Week 120 | -11.93 ± 2.685 | -11.98 ± 2.291 |
| Change at Week 144 | -19.49 ± 3.892 | -17.67 ± 4.061 |
Change from baseline to post-baseline visits in Brief Fatigue Inventory Question 3 (Worst Fatigue in Past 24 Hours; BFI-Q3) as averaged from daily diary scores recorded over 1 week and the study visit score. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue rated on a 0 to 10 numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). Participants are asked to rate their worst fatigue over the past 24 hours from 0 (no fatigue) to 10 (as bad a you can imagine). The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -0.53 ± 0.266 | -0.44 ± 0.261 |
| Change at Week 24 | -0.45 ± 0.298 | -0.65 ± 0.280 |
| Change at Week 36 | -1.23 ± 0.305 | -0.90 ± 0.271 |
| Change at Week 48 | -1.21 ± 0.317 | -0.99 ± 0.295 |
| Change at Week 72 | -0.79 ± 0.352 | -0.58 ± 0.309 |
| Change at Week 96 | -0.82 ± 0.362 | -0.75 ± 0.306 |
Change from baseline to post-baseline visits in BFI global fatigue score, calculated by averaging all 9 BFI items as recorded on the day of the study visit. The BFI is a self-reported questionnaire consisting of 9 items related to fatigue that are rated on a numerical scale with a recall period of 24 hours. Two dimensions are measured: fatigue severity and the interference of fatigue on daily life (activity, mood, walking ability, work, relations with others, and enjoyment of life). BFI Global Fatigue score was calculated by averaging all 9 items on the BFI. Global scores range from 0 to 10, with higher score indicating worse fatigue severity and interference. The GEE Estimates are from the GEE model which includes the change from baseline for each BFI endpoint as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of each BFI endpoint as a covariate, with compound symmetry covariance structure.
| score on a scale | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -0.14 ± 0.262 | -0.18 ± 0.261 |
| Change at Week 24 | -0.08 ± 0.292 | 0.05 ± 0.261 |
| Change at Week 36 | -0.69 ± 0.315 | -0.54 ± 0.283 |
| Change at Week 48 | -0.75 ± 0.303 | -0.45 ± 0.275 |
| Change at Week 72 | -0.72 ± 0.304 | -0.78 ± 0.266 |
| Change at Week 96 | -0.86 ± 0.291 | -0.80 ± 0.285 |
| ng/mL | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -1.86 ± 5.958 | 96.22 ± 14.264 |
| Change at Week 24 | 2.95 ± 6.423 | 63.50 ± 7.239 |
| Change at Week 36 | 100.00 ± 10.562 | 49.71 ± 6.786 |
| Change at Week 48 | 85.12 ± 11.037 | 40.07 ± 7.292 |
| Change at Week 72 | 48.98 ± 7.286 | 18.04 ± 9.186 |
| Change at Week 96 | 22.98 ± 7.075 | 12.48 ± 8.661 |
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 2.30 ± 6.318 | 91.78 ± 10.787 |
| Change at Week 24 | 7.83 ± 7.076 | 72.43 ± 8.519 |
| Change at Week 36 | 116.39 ± 9.726 | 63.58 ± 8.562 |
| Change a Week 48 | 99.10 ± 11.442 | 56.51 ± 8.771 |
| Change at Week 72 | 72.56 ± 10.055 | 38.82 ± 10.225 |
| Change at Week 96 | 41.62 ± 8.163 | 31.04 ± 8.126 |
The GEE Estimates are from the GEE model which includes the change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
| pg/mL | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 26.96 ± 35.689 | 322.09 ± 56.924 |
| Change at Week 24 | -4.20 ± 34.835 | 184.56 ± 39.213 |
| Change at Week 36 | 350.89 ± 53.131 | 193.50 ± 39.461 |
| Change at Week 48 | 310.67 ± 45.003 | 138.61 ± 37.886 |
| Change at Week 72 | 178.03 ± 42.702 | 51.59 ± 42.863 |
| Change at Week 96 | 79.04 ± 45.622 | 10.84 ± 40.761 |
The GEE Estimates are from the GEE model which includes the percent change from baseline for CTx as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 9.64 ± 5.671 | 45.40 ± 7.267 |
| Change at Week 24 | 4.75 ± 5.280 | 32.48 ± 6.414 |
| Change at Week 36 | 61.31 ± 10.653 | 34.07 ± 6.250 |
| Change at Week 48 | 50.35 ± 6.464 | 28.33 ± 5.354 |
| Change at Week 72 | 34.78 ± 7.007 | 17.09 ± 5.957 |
| Change at Week 96 | 27.38 ± 7.783 | 13.47 ± 5.952 |
The GEE Estimates are from the GEE model which includes the change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of BALP as a covariate, with compound symmetry covariance structure.
| μg/L | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | -2.11 ± 1.529 | 6.52 ± 2.832 |
| Change at Week 24 | 1.03 ± 1.801 | 5.70 ± 2.038 |
| Change at Week 36 | 10.42 ± 2.017 | 4.46 ± 1.607 |
| Change at Week 48 | 6.69 ± 1.929 | 0.23 ± 1.830 |
| Change at Week 72 | -0.92 ± 1.779 | -3.39 ± 1.739 |
| Change at Week 96 | -2.49 ± 1.887 | -2.76 ± 1.640 |
The GEE Estimates are from the GEE model which includes the percent change from baseline for BALP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 7.85 ± 9.867 | 30.29 ± 13.476 |
| Change at Week 24 | 27.56 ± 10.339 | 39.13 ± 10.902 |
| Change at Week 36 | 64.41 ± 11.669 | 43.13 ± 11.473 |
| Change at Week 48 | 50.65 ± 11.317 | 23.46 ± 10.041 |
| Change at Week 72 | 19.79 ± 11.755 | 14.40 ± 11.618 |
| Change at Week 96 | 16.46 ± 11.027 | 21.21 ± 9.688 |
The GEE Estimates are from the GEE model which includes the change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
| mmol/L | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 1 | -0.01 ± 0.024 | 0.44 ± 0.031 |
| Change at Week 2 | -0.03 ± 0.023 | 0.43 ± 0.032 |
| Change at Week 4 | -0.03 ± 0.022 | 0.27 ± 0.034 |
| Change at Week 6 | -0.00 ± 0.023 | 0.45 ± 0.036 |
| Change at Week 10 | 0.01 ± 0.022 | 0.37 ± 0.033 |
| Change at Week 12 | -0.01 ± 0.023 | 0.17 ± 0.032 |
| Change at Week 14 | 0.02 ± 0.022 | 0.32 ± 0.032 |
| Change at Week 18 | 0.02 ± 0.023 | 0.32 ± 0.031 |
| Change at Week 20 | -0.01 ± 0.023 | 0.18 ± 0.028 |
| Change at Week 21 | -0.00 ± 0.024 | 0.31 ± 0.033 |
| Change at Week 22 | -0.02 ± 0.022 | 0.25 ± 0.033 |
| Change at Week 24 | -0.00 ± 0.023 | 0.13 ± 0.028 |
| Change at Week 26 | 0.47 ± 0.035 | 0.31 ± 0.032 |
| Change at Week 28 | 0.28 ± 0.028 | 0.18 ± 0.028 |
| Change at Week 34 | 0.36 ± 0.029 | 0.28 ± 0.031 |
| Change at Week 36 | 0.17 ± 0.026 | 0.13 ± 0.027 |
| Change at Week 46 | 0.31 ± 0.026 | 0.27 ± 0.030 |
| Change at Week 48 | 0.13 ± 0.027 | 0.11 ± 0.027 |
| Change at Week 60 | 0.14 ± 0.028 | 0.11 ± 0.028 |
| Change at Week 70 | 0.30 ± 0.029 | 0.30 ± 0.030 |
| Change at Week 72 | 0.13 ± 0.025 | 0.11 ± 0.027 |
| Change at Week 84 | 0.12 ± 0.025 | 0.14 ± 0.027 |
| Change at Week 94 | 0.25 ± 0.029 | 0.30 ± 0.029 |
| Change at Week 96 | 0.07 ± 0.026 | 0.13 ± 0.025 |
| Change at Week 108 | 0.11 ± 0.028 | 0.13 ± 0.031 |
| Change at Week 120 | 0.09 ± 0.027 | 0.13 ± 0.033 |
| Change at Week 132 | 0.12 ± 0.033 | 0.15 ± 0.036 |
| Change at Week 144 | 0.05 ± 0.064 | — |
The GEE Estimates are from the GEE model which includes the percent change from baseline for serum phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of serum phosphorus as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 1 | -1.11 ± 3.936 | 69.24 ± 4.762 |
| Change at Week 2 | -5.91 ± 3.969 | 69.39 ± 4.881 |
| Change at Week 4 | -4.84 ± 3.792 | 42.89 ± 5.325 |
| Change at Week 6 | -0.41 ± 3.951 | 72.96 ± 5.944 |
| Change at Week 10 | 2.40 ± 3.680 | 59.96 ± 5.356 |
| Change at Week 12 | -2.14 ± 3.798 | 29.50 ± 5.087 |
| Change at Week 14 | 3.58 ± 3.691 | 52.14 ± 5.194 |
| Change at Week 18 | 3.93 ± 3.857 | 53.22 ± 5.106 |
| Change at Week 20 | -1.81 ± 3.759 | 31.28 ± 4.472 |
| Change at Week 21 | 0.21 ± 4.011 | 50.59 ± 5.123 |
| Change at Week 22 | -3.42 ± 3.709 | 40.98 ± 5.196 |
| Change at Week 24 | -0.61 ± 3.802 | 22.01 ± 4.523 |
| Change at Week 26 | 78.30 ± 5.993 | 51.51 ± 5.204 |
| Change at Week 28 | 46.07 ± 4.766 | 31.32 ± 4.415 |
| Change at Week 34 | 59.18 ± 4.959 | 45.83 ± 4.871 |
| Change at Week 36 | 28.03 ± 4.424 | 22.34 ± 4.256 |
| Change at Week 46 | 51.49 ± 4.380 | 45.39 ± 5.018 |
| Change at Week 48 | 21.58 ± 4.365 | 19.12 ± 4.190 |
| Change at Week 60 | 22.90 ± 4.338 | 19.60 ± 4.436 |
| Change at Week 70 | 50.22 ± 4.916 | 47.81 ± 4.768 |
| Change at Week 72 | 21.59 ± 4.155 | 19.45 ± 4.344 |
| Change at Week 84 | 21.47 ± 4.089 | 23.58 ± 4.200 |
| Change at Week 94 | 43.67 ± 4.834 | 49.36 ± 4.501 |
| Change at Week 96 | 12.97 ± 4.216 | 21.65 ± 3.854 |
| Change at Week 108 | 19.21 ± 4.665 | 23.39 ± 4.749 |
| Change at Week 120 | 15.13 ± 4.365 | 21.50 ± 5.268 |
| Change at Week 132 | 20.43 ± 5.362 | 25.34 ± 5.847 |
| Change at Week 144 | 5.49 ± 12.212 | — |
The GEE Estimates are from the GEE model which includes the change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
| pg/mL | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 1 | 2.04 ± 2.251 | 87.23 ± 5.500 |
| Change at Week 2 | 1.40 ± 2.113 | 58.20 ± 3.931 |
| Change at Week 4 | 2.61 ± 2.300 | 20.55 ± 2.828 |
| Change at Week 20 | 2.88 ± 2.163 | 8.11 ± 2.294 |
| Change at Week 21 | 3.09 ± 2.177 | 33.95 ± 3.019 |
| Change at Week 22 | 3.45 ± 2.289 | 26.10 ± 2.952 |
| Change at Week 46 | 25.23 ± 2.576 | 23.08 ± 3.243 |
| Change at Week 48 | 10.50 ± 2.418 | 7.24 ± 2.449 |
| Change at Week 60 | 9.29 ± 2.336 | 5.69 ± 2.583 |
| Change at Week 70 | 24.20 ± 2.529 | 18.82 ± 2.486 |
| Change at Week 72 | 7.12 ± 2.424 | 5.52 ± 2.607 |
| Change at Week 84 | 5.13 ± 2.388 | 1.16 ± 2.549 |
| Change at Week 94 | 18.96 ± 2.655 | 15.26 ± 2.502 |
| Change at Week 96 | 3.43 ± 2.348 | 1.95 ± 2.356 |
| Change at Week 108 | 4.76 ± 2.349 | 4.29 ± 2.672 |
| Change at Week 120 | 4.64 ± 2.496 | 5.37 ± 2.935 |
| Change at Week 132 | 4.08 ± 3.142 | 8.05 ± 4.227 |
| Change at Week 144 | -0.38 ± 4.677 | — |
The GEE Estimates are from the GEE model which includes the percent change from baseline for 1,25(OH)2D as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 1 | 10.45 ± 13.041 | 310.72 ± 23.225 |
| Change at Week 2 | 10.53 ± 12.760 | 207.90 ± 16.728 |
| Change at Week 4 | 16.07 ± 12.810 | 76.22 ± 12.147 |
| Change at Week 20 | 21.36 ± 12.424 | 41.08 ± 11.943 |
| Change at Week 21 | 21.51 ± 12.825 | 131.76 ± 14.862 |
| Change at Week 22 | 21.07 ± 12.725 | 102.81 ± 14.619 |
| Change at Week 46 | 130.29 ± 22.718 | 96.63 ± 16.909 |
| Change at Week 48 | 70.09 ± 17.114 | 34.47 ± 12.903 |
| Change at Week 60 | 65.46 ± 13.083 | 32.32 ± 12.230 |
| Change at Week 70 | 123.58 ± 17.315 | 82.03 ± 12.604 |
| Change at Week 72 | 58.45 ± 13.957 | 31.14 ± 13.070 |
| Change at Week 84 | 55.67 ± 15.323 | 18.83 ± 12.801 |
| Change at Week 94 | 111.25 ± 21.970 | 71.30 ± 12.280 |
| Change at Week 96 | 50.17 ± 18.857 | 22.15 ± 10.487 |
| Change at Week 108 | 44.78 ± 14.219 | 29.16 ± 13.326 |
| Change at Week 120 | 58.37 ± 19.621 | 36.09 ± 13.089 |
| Change at Week 132 | 67.59 ± 35.770 | 42.55 ± 15.925 |
| Change at Week 144 | 22.65 ± 19.297 | — |
The GEE Estimates are from the GEE model which includes the change from baseline for 24-Hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
| g/24 hour | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 0.06 ± 0.052 | 0.05 ± 0.046 |
| Change at Week 24 | 0.07 ± 0.065 | 0.05 ± 0.046 |
| Change at Week 36 | 0.04 ± 0.054 | 0.07 ± 0.045 |
| Change at Week 48 | 0.07 ± 0.060 | 0.13 ± 0.067 |
| Change at Week 72 | 0.08 ± 0.065 | 0.05 ± 0.052 |
| Change at Week 96 | 0.10 ± 0.075 | 0.10 ± 0.054 |
The GEE Estimates are from the GEE model which includes the percent change from baseline for 24-hour urinary phosphorus as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of urinary phosphorus as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 12 | 21.91 ± 11.844 | 21.40 ± 11.453 |
| Change at Week 24 | 28.45 ± 15.518 | 20.35 ± 11.567 |
| Change at Week 36 | 18.19 ± 11.784 | 28.31 ± 12.173 |
| Change at Week 48 | 27.32 ± 14.328 | 37.50 ± 14.687 |
| Change at Week 72 | 29.53 ± 14.485 | 25.80 ± 15.476 |
| Change at Week 96 | 31.17 ± 17.248 | 30.64 ± 10.420 |
The GEE Estimates are from the GEE model which includes the change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
| mg/dL | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 2 | -0.02 ± 0.072 | 1.60 ± 0.121 |
| Change at Week 4 | -0.03 ± 0.070 | 0.91 ± 0.117 |
| Change at Week 12 | 0.11 ± 0.082 | 0.70 ± 0.107 |
| Change at Week 22 | 0.02 ± 0.069 | 1.01 ± 0.123 |
| Change at Week 24 | 0.07 ± 0.071 | 0.51 ± 0.093 |
| Change at Week 48 | 0.55 ± 0.087 | 0.48 ± 0.091 |
| Change at Week 60 | 0.57 ± 0.097 | 0.43 ± 0.086 |
| Change at Week 72 | 0.55 ± 0.086 | 0.43 ± 0.091 |
| Change at Week 84 | 0.49 ± 0.078 | 0.42 ± 0.092 |
| Change at Week 96 | 0.29 ± 0.086 | 0.46 ± 0.084 |
The GEE Estimates are from the GEE model which includes the percent change from baseline for TmP/GFR as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 2 | -2.15 ± 4.515 | 100.10 ± 7.222 |
| Change at Week 4 | -2.73 ± 4.416 | 56.53 ± 6.816 |
| Change at Week 12 | 6.28 ± 4.900 | 43.65 ± 6.206 |
| Change at Week 22 | 1.38 ± 4.252 | 62.38 ± 7.144 |
| Change at Week 24 | 3.63 ± 4.460 | 33.02 ± 5.464 |
| Change at Week 48 | 35.52 ± 5.390 | 31.02 ± 5.489 |
| Change at Week 60 | 37.13 ± 5.855 | 27.49 ± 5.002 |
| Change at Week 72 | 35.89 ± 5.492 | 28.98 ± 5.513 |
| Change at Week 84 | 33.15 ± 4.924 | 27.69 ± 5.527 |
| Change at Week 96 | 19.95 ± 5.417 | 29.67 ± 4.759 |
The GEE Estimates are from the GEE model which includes the change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
| fraction of phosphate reabsorbed | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 2 | -0.02 ± 0.013 | 0.07 ± 0.008 |
| Change at Week 4 | -0.03 ± 0.012 | 0.03 ± 0.009 |
| Change at Week 12 | -0.00 ± 0.010 | 0.04 ± 0.008 |
| Change at Week 22 | -0.01 ± 0.009 | 0.05 ± 0.011 |
| Change at Week 24 | -0.02 ± 0.012 | 0.03 ± 0.009 |
| Change at Week 48 | 0.02 ± 0.012 | 0.03 ± 0.009 |
| Change at Week 60 | 0.03 ± 0.009 | 0.02 ± 0.009 |
| Change at Week 72 | 0.02 ± 0.011 | 0.02 ± 0.011 |
| Change at Week 84 | 0.02 ± 0.010 | 0.01 ± 0.012 |
| Change at Week 96 | -0.01 ± 0.014 | 0.03 ± 0.009 |
The GEE Estimates are from the GEE model which includes the percent change from baseline for TRP as the dependent variable, region, visit, treatment, actual randomization stratification and visit by treatment as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
| percentage change | Placebo | Burosumab 1 mg/kg |
|---|---|---|
| Change at Week 2 | -2.00 ± 1.530 | 9.81 ± 1.111 |
| Change at Week 4 | -3.75 ± 1.486 | 4.86 ± 1.114 |
| Change at Week 12 | 0.56 ± 1.261 | 5.45 ± 1.079 |
| Change at Week 22 | -0.01 ± 1.163 | 7.03 ± 1.451 |
| Change at Week 24 | -1.56 ± 1.579 | 4.21 ± 1.141 |
| Change at Week 48 | 3.95 ± 1.547 | 4.70 ± 1.183 |
| Change at Week 60 | 3.99 ± 1.096 | 3.00 ± 1.123 |
| Change at Week 72 | 3.90 ± 1.427 | 3.24 ± 1.414 |
| Change at Week 84 | 3.78 ± 1.276 | 1.97 ± 1.516 |
| Change at Week 96 | -0.09 ± 1.582 | 4.44 ± 1.116 |
| percentage of participants | Placebo | Burosumab |
|---|---|---|
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN (2.5 mg/dL [0.81 mmol/L]) at the End of the Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 6.1 (2.4 to 14.6) | 67.6 (55.8 to 77.6) |
| mg/dL | Placebo | Burosumab |
|---|---|---|
| Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.16 ± 0.272 | 1.21 ± 0.513 |
| percentage change | Placebo | Burosumab |
|---|---|---|
| Percent Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 9.85 ± 15.292 | 61.44 ± 28.961 |
| mg/dL | Placebo | Burosumab |
|---|---|---|
| Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.13 ± 0.265 | 0.69 ± 0.392 |
| percentage change | Placebo | Burosumab |
|---|---|---|
| Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 7.83 ± 14.755 | 35.18 ± 20.731 |
| mg/dL | Placebo | Burosumab |
|---|---|---|
| Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | 2.08 ± 0.292 | 3.08 ± 0.477 |
Collected over From first dose of study drug through the end of study plus 4 weeks (+ 5 days). Mean (SE) duration of exposure to burosumab for all periods combined through EOS II was 771.3 (21.97) days (range: 167 - 957) in the burosumab->burosumab group and 625.7 (19.40) days (range: 165 - 844) in the placebo->burosumab group.. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Placebo (DB Period) | 0/66 (0%) | 1/66 (1.5%) | 57/66 (86.4%) |
| Placebo -> Burosumab (OL Period) | 0/66 (0%) | 10/66 (15.2%) | 63/66 (95.5%) |
| Burosumab -> Burosumab (Combined DB and OL Period) | 1/68 (1.5%) | 12/68 (17.6%) | 68/68 (100%) |
| Total Burosumab (Combined DB and OL Period) | 1/134 (0.7%) | 22/134 (16.4%) | 131/134 (97.8%) |
| Event | Placebo (DB Period) | Placebo -> Burosumab (OL Period) | Burosumab -> Burosumab (Combined DB and OL Period) | Total Burosumab (Combined DB and OL Period) |
|---|---|---|---|---|
| MyelopathyNervous system disorders | 0/66 | 0/66 | 2/68 | 2/134 |
| PalpitationsCardiac disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| Periodontal DiseaseGastrointestinal disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| Peritoneal AdhesionsGastrointestinal disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| Subdural HaematomaInjury, poisoning and procedural complications | 0/66 | 1/66 | 0/68 | 1/134 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 0/66 | 1/66 | 1/68 | 2/134 |
| Cervical Spinal StenosisMusculoskeletal and connective tissue disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| Joint Range Of Motion DecreasedMusculoskeletal and connective tissue disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| PseudarthrosisMusculoskeletal and connective tissue disorders | 0/66 | 1/66 | 0/68 | 1/134 |
| Invasive Ductal Breast CarcinomaNeoplasms benign, malignant and unspecified (incl cysts and polyps) | 1/66 | 0/66 | 0/68 | 0/134 |
| Event | Placebo (DB Period) | Placebo -> Burosumab (OL Period) | Burosumab -> Burosumab (Combined DB and OL Period) | Total Burosumab (Combined DB and OL Period) |
|---|---|---|---|---|
| NasopharyngitisInfections and infestations | 6/66 | 24/66 | 28/68 | 52/134 |
| ArthralgiaMusculoskeletal and connective tissue disorders | 16/66 | 23/66 | 27/68 | 50/134 |
| HeadacheNervous system disorders | 5/66 | 18/66 | 22/68 | 40/134 |
| Tooth AbscessInfections and infestations | 6/66 | 5/66 | 19/68 | 24/134 |
| Back PainMusculoskeletal and connective tissue disorders | 6/66 | 17/66 | 18/68 | 35/134 |
| Pain In ExtremityMusculoskeletal and connective tissue disorders | 10/66 | 10/66 | 18/68 | 28/134 |
| FatigueGeneral disorders | 7/66 | 14/66 | 16/68 | 30/134 |
| Vitamin D DeficiencyMetabolism and nutrition disorders | 3/66 | 7/66 | 15/68 | 22/134 |
| DiarrhoeaGastrointestinal disorders | 5/66 | 5/66 | 13/68 | 18/134 |
| ToothacheGastrointestinal disorders | 1/66 | 10/66 | 12/68 | 22/134 |
| Age, Continuous(years) | Placebo | Burosumab | Total |
|---|---|---|---|
| Mean | 38.65 ± 12.756 | 41.29 ± 11.582 | 39.99 ± 12.201 |
| Sex: Female, Male(Participants) | Placebo | Burosumab | Total |
|---|---|---|---|
| Female | 43 | 44 | 87 |
| Male | 23 | 24 | 47 |
| Ethnicity (NIH/OMB)(Participants) | Placebo | Burosumab | Total |
|---|---|---|---|
| Hispanic or Latino | 5 | 7 | 12 |
| Not Hispanic or Latino | 61 | 61 | 122 |
| Unknown or Not Reported | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Placebo | Burosumab | Total |
|---|---|---|---|
| Asian | 9 | 12 | 21 |
| Black or African American | 3 | 0 | 3 |
| White | 53 | 55 | 108 |
| Other, Not Specified | 1 | 1 | 2 |
| Brief Pain Inventory (BPI) Worst Pain Score(score on a scale) | Placebo | Burosumab | Total |
|---|---|---|---|
| Mean | 6.54 ± 1.433 | 6.81 ± 1.308 | 6.68 ± 1.372 |
| BPI Pain Severity Score(score on a scale) | Placebo | Burosumab | Total |
|---|---|---|---|
| Mean | 4.92 ± 1.547 | 5.18 ± 1.531 | 5.05 ± 1.539 |
| BPI Pain Interference Score(score on a scale) | Placebo | Burosumab | Total |
|---|---|---|---|
| Mean | 4.76 ± 2.174 | 5.23 ± 2.237 | 5.00 ± 2.210 |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score(score on a scale) | Placebo | Burosumab | Total |
|---|---|---|---|
| Mean | 61.36 ± 20.770 | 64.71 ± 20.253 | 63.06 ± 20.500 |
11 further baseline measures are reported on the registry.
Ran from Oct 2015 to primary completion in Dec 2016, 14 months.
Results were first posted in Feb 2021, 4 years 1 month after primary completion. A results delay was requested in Dec 2017.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Jun 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions 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.
Studies of the drug tested here: Burosumab
Familial Hypophosphatemic Rickets →