X-linked Hypophosphatemia
Conditions
Keywords
KRN23, Fibroblast growth factor 23 (FGF23), XLH, X-linked hypophosphatemia, burosumab, Crysvita
Brief summary
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.
Interventions
BIOLOGICALburosumab
solution for SC injection
OTHERPlacebo
saline solution for SC injection
Sponsors
Kyowa Kirin Co., Ltd.
Kyowa Kirin, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female, aged 18 - 65 years, inclusive 2. 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: * Documented phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) mutation in the patient or a directly related family member with appropriate X-linked inheritance * Serum intact FGF23 (iFGF23) level \> 30 pg/mL by Kainos assay 3. Biochemical findings consistent with XLH at Screening Visit 2 following overnight fasting (min. 8 hours): * Serum phosphorus \< 2.5 mg/dL * TmP/GFR of \< 2.5 mg/dL 4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4 on Brief Pain Inventory (BPI) Questions 3 (Worst Pain) at Screening Visit 1. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia-for example, back or joint pain in the presence of severe osteoarthritis by radiograph in that anatomical location-in the absence of any skeletal pain likely attributed to XLH/osteomalacia should not be considered for eligibility) 5. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min (using the Chronic Kidney Disease Epidemiology Collaboration \[CKD-EPI\] equation) or eGFR of 45 60 mL/min at Screening Visit 2 with confirmation that the renal insufficiency is not due to nephrocalcinosis 6. If taking chronic pain medications (including narcotic pain medications/opioids), must be on a stable regimen for at least 21 days prior to Screening Visit 1, and be willing to maintain medications at the same stable dose(s) and schedule throughout the Placebo-controlled Treatment Period of the study. The dose must not exceed 60 mg oral morphine equivalents/day 7. Provide written informed consent or if a minor, provide written consent and have a legally authorized representative willing and able to provide written informed consent, after the nature of the study has been explained, and prior to any research-related procedures 8. Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history 9. Females of child-bearing potential must have a negative urine pregnancy test at Screening and be willing to have additional pregnancy tests during the study. Females considered not to be of childbearing potential include those who have been in menopause for at least two years prior to Screening, or have had tubal ligation at least one year prior to Screening, or have had a total hysterectomy or bilateral salpingo-oophorectomy 10. Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a bilateral salpingo-oophorectomy and are sexually active must consent to use an effective method of contraception as determined by the site investigator (i.e. oral hormonal contraceptives, patch hormonal contraceptives, vaginal ring, intrauterine device, physical double-barrier methods, surgical hysterectomy, vasectomy, tubal ligation, or true abstinence) from the period following the signing of the informed consent through 12 weeks after last dose of study drug 11. Must, in the opinion of the investigator, be willing and able to complete all aspects of the study, adhere to the study visit schedule and comply with the assessments 12. Must have completed at least 4 of 7 days of the patient diaries before the Baseline visit.
Exclusion criteria
1. Use of a pharmacologic vitamin D metabolite or analog (calcitriol, doxercalciferol, and paricalcitol) within 14 days prior to Screening Visit 2 2. Use of oral phosphate within 14 days prior to Screening Visit 2 3. Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening Visit 2 4. Chronic use of systemic corticosteroids defined as more than 10 days in the previous 2 months 5. Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening Visit 2 6. Serum intact parathyroid hormone (iPTH) ≥ 2.5 upper limit of normal (ULN) at Screening Visit 1 7. Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example) within 60 days prior to Screening Visit 1 8. Use of oral bisphosphonates for 6 months or more in the 2 years prior to Screening Visit 1 9. Use of denosumab in the 6 months prior to Screening Visit 1 10. Use of teriparatide in the 2 months prior to Screening Visit 1 11. Planned or recommended orthopedic surgery within the first 24 weeks of the clinical trial period 12. History of traumatic fracture or orthopedic surgery within 6 months prior to Screening Visit 1 13. Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening Visit 1 14. Use of any investigational 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. 15. Pregnant or breastfeeding at Screening /Baseline or planning to become pregnant (self or partner) at any time during the study 16. Unable or unwilling to withhold prohibited medications throughout the study 17. Presence or history of any hypersensitivity, allergic or anaphylactic reactions to any monoclonal antibody or KRN23 excipients that, in the judgment of the investigator, places the subject at increased risk for adverse effects. 18. Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody 19. History of recurrent infection or predisposition to infection, or of known immunodeficiency 20. Presence of malignant neoplasm (except basal cell carcinoma) 21. Presence of a concurrent disease or condition that would interfere with study participation or affect safety 22. Presence or history of any condition that, in the view of the investigator, places the subject at high risk of poor treatment compliance or of not completing the study
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 | Baseline through Week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score | Baseline, 24 weeks | 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. |
| Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score | Baseline, 24 weeks | 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. |
| Change From Baseline to Week 24 in the WOMAC Physical Function Score | Baseline, 24 weeks | 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. |
| Change From Baseline Over Time in BPI Worst Pain Score | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in BPI Pain Severity Score | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in BPI Pain Interference Score | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in WOMAC Stiffness Score | Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144 | 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. |
| Change From Baseline Over Time in WOMAC Physical Function Score | Baseline, Weeks 12, 24, 36, 48, 72, 96, 120, 144 | 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. |
| Change From Baseline Over Time in BFI Worst Fatigue Score | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in BFI Global Fatigue Score | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Baseline, Weeks 12, 24, 36, 48, 72, 96 | — |
| Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | 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) | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Baseline, Weeks 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in Serum Phosphorus | 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 | 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. |
| Percent Change From Baseline Over Time in Serum Phosphorus | 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 | 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. |
| Change From Baseline Over Time in Serum 1,25(OH)2D | Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144 | 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. |
| Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Baseline, Weeks 1, 2, 4, 20, 21, 22, 46, 48, 60, 70, 72, 84, 94, 96, 108, 120, 132, 144 | 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. |
| Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Baseline, Week 12, 24, 36, 48, 72, 96 | 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. |
| Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Baseline, Week 12, 24, 36, 48, 72, 96 | 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. |
| Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96 | 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. |
| Percent Change From Baseline Over Time in TmP/GFR | Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96 | 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. |
| Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96 | 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. |
| Percent Change From Baseline Over Time in TRP | Baseline, Weeks 2, 4, 12, 22, 24, 48, 60, 72, 84, 96 | 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 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 | 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 | 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 | 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 | 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 | Baseline through Week 24 | — |
| Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | Baseline through Week 24 | — |
Countries
France, Ireland, Italy, Japan, South Korea, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo Placebo SC Q4W through Week 24 | 66 |
| Burosumab Burosumab 1 mg/kg SC Q4W | 68 |
| Total | 134 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Double-Blind (Placebo-Controlled) Period | Withdrawal by Subject | 0 | 1 |
| Open-label Treatment Continuation Period | Other, Not Specified | 3 | 3 |
| Open-label Treatment Continuation Period | Withdrawal by Subject | 0 | 1 |
| Open-Label Treatment Extension Period I | Death | 0 | 1 |
| Open-Label Treatment Extension Period I | Lost to Follow-up | 0 | 1 |
| Open-Label Treatment Extension Period I | Other, Not Specified | 3 | 1 |
| Open-Label Treatment Extension Period I | Withdrawal by Subject | 0 | 1 |
| Open-Label Treatment Extension Period II | Other, Not Specified | 1 | 0 |
Baseline characteristics
| Characteristic | Total | Burosumab | Placebo |
|---|---|---|---|
| 24-Hour Urinary Phosphorus | 0.77 g/24 hour STANDARD_DEVIATION 0.255 | 0.72 g/24 hour STANDARD_DEVIATION 0.241 | 0.81 g/24 hour STANDARD_DEVIATION 0.262 |
| Age, Continuous | 39.99 years STANDARD_DEVIATION 12.201 | 41.29 years STANDARD_DEVIATION 11.582 | 38.65 years STANDARD_DEVIATION 12.756 |
| BFI Global Fatigue Score | 5.12 score on a scale STANDARD_DEVIATION 1.999 | 5.37 score on a scale STANDARD_DEVIATION 2.044 | 4.86 score on a scale STANDARD_DEVIATION 1.932 |
| BPI Pain Interference Score | 5.00 score on a scale STANDARD_DEVIATION 2.21 | 5.23 score on a scale STANDARD_DEVIATION 2.237 | 4.76 score on a scale STANDARD_DEVIATION 2.174 |
| BPI Pain Severity Score | 5.05 score on a scale STANDARD_DEVIATION 1.539 | 5.18 score on a scale STANDARD_DEVIATION 1.531 | 4.92 score on a scale STANDARD_DEVIATION 1.547 |
| Brief Fatigue Inventory (BFI) Worst Fatigue Score | 6.84 score on a scale STANDARD_DEVIATION 1.591 | 6.94 score on a scale STANDARD_DEVIATION 1.657 | 6.74 score on a scale STANDARD_DEVIATION 1.526 |
| Brief Pain Inventory (BPI) Worst Pain Score | 6.68 score on a scale STANDARD_DEVIATION 1.372 | 6.81 score on a scale STANDARD_DEVIATION 1.308 | 6.54 score on a scale STANDARD_DEVIATION 1.433 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 7 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 122 Participants | 61 Participants | 61 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 21 Participants | 12 Participants | 9 Participants |
| Race/Ethnicity, Customized Black or African American | 3 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Other, Not Specified | 2 Participants | 1 Participants | 1 Participants |
| Race/Ethnicity, Customized White | 108 Participants | 55 Participants | 53 Participants |
| Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR) | 1.639 mg/dL STANDARD_DEVIATION 0.386 | 1.678 mg/dL STANDARD_DEVIATION 0.4004 | 1.598 mg/dL STANDARD_DEVIATION 0.3693 |
| Serum 1, 25 (OH)2 D | 33.0 pg/mL STANDARD_DEVIATION 14.28 | 32.4 pg/mL STANDARD_DEVIATION 12.96 | 33.5 pg/mL STANDARD_DEVIATION 15.61 |
| Serum Bone-Specific Alkaline Phosphatase (BALP) | 24.9 μg/L STANDARD_DEVIATION 19.47 | 25.1 μg/L STANDARD_DEVIATION 21.55 | 24.6 μg/L STANDARD_DEVIATION 17.3 |
| Serum Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | 718.8 pg/mL STANDARD_DEVIATION 414.89 | 718.4 pg/mL STANDARD_DEVIATION 413.71 | 719.2 pg/mL STANDARD_DEVIATION 419.24 |
| Serum Phosphorus | 0.635 mmol/L STANDARD_DEVIATION 0.105 | 0.653 mmol/L STANDARD_DEVIATION 0.1072 | 0.617 mmol/L STANDARD_DEVIATION 0.1001 |
| Serum Procollagen Type 1 N- Propeptide (P1NP) | 87.6 ng/mL STANDARD_DEVIATION 53.3 | 87.5 ng/mL STANDARD_DEVIATION 53.6 | 87.6 ng/mL STANDARD_DEVIATION 53.41 |
| Sex: Female, Male Female | 87 Participants | 44 Participants | 43 Participants |
| Sex: Female, Male Male | 47 Participants | 24 Participants | 23 Participants |
| Tubular Reabsorption of Phosphate (TRP) | 0.810 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0834 | 0.807 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0832 | 0.812 fraction of phosphate reabsorbed STANDARD_DEVIATION 0.0842 |
| Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Stiffness Score | 63.06 score on a scale STANDARD_DEVIATION 20.5 | 64.71 score on a scale STANDARD_DEVIATION 20.253 | 61.36 score on a scale STANDARD_DEVIATION 20.77 |
| WOMAC Physical Function Score | 47.40 score on a scale STANDARD_DEVIATION 20.024 | 50.79 score on a scale STANDARD_DEVIATION 19.66 | 43.89 score on a scale STANDARD_DEVIATION 19.938 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 66 | 0 / 66 | 1 / 68 | 1 / 134 |
| other Total, other adverse events | 57 / 66 | 63 / 66 | 68 / 68 | 131 / 134 |
| serious Total, serious adverse events | 1 / 66 | 10 / 66 | 12 / 68 | 22 / 134 |
Outcome results
Primary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Placebo | 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 percentage of participants |
| 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 | 92.6 percentage of participants |
p-value: <0.0001Cochran-Mantel-Haenszel
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.13 mg/dL | Standard Deviation 0.265 |
| Burosumab | Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.69 mg/dL | Standard Deviation 0.392 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 mg/dL | Standard Deviation 0.272 |
| Burosumab | Change From Baseline in Serum Phosphorus at Each Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 1.21 mg/dL | Standard Deviation 0.513 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 12 | 0.06 g/24 hour | Standard Error 0.052 |
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 24 | 0.07 g/24 hour | Standard Error 0.065 |
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 36 | 0.04 g/24 hour | Standard Error 0.054 |
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 48 | 0.07 g/24 hour | Standard Error 0.06 |
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 72 | 0.08 g/24 hour | Standard Error 0.065 |
| Placebo | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 96 | 0.10 g/24 hour | Standard Error 0.075 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 72 | 0.05 g/24 hour | Standard Error 0.052 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 12 | 0.05 g/24 hour | Standard Error 0.046 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 48 | 0.13 g/24 hour | Standard Error 0.067 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 24 | 0.05 g/24 hour | Standard Error 0.046 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 96 | 0.10 g/24 hour | Standard Error 0.054 |
| Burosumab | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 36 | 0.07 g/24 hour | Standard Error 0.045 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 12 | -0.14 score on a scale | Standard Error 0.262 |
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 24 | -0.08 score on a scale | Standard Error 0.292 |
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 36 | -0.69 score on a scale | Standard Error 0.315 |
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 48 | -0.75 score on a scale | Standard Error 0.303 |
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 72 | -0.72 score on a scale | Standard Error 0.304 |
| Placebo | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 96 | -0.86 score on a scale | Standard Error 0.291 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 72 | -0.78 score on a scale | Standard Error 0.266 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 12 | -0.18 score on a scale | Standard Error 0.261 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 48 | -0.45 score on a scale | Standard Error 0.275 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 24 | 0.05 score on a scale | Standard Error 0.261 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 96 | -0.80 score on a scale | Standard Error 0.285 |
| Burosumab | Change From Baseline Over Time in BFI Global Fatigue Score | Change at Week 36 | -0.54 score on a scale | Standard Error 0.283 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 12 | -0.53 score on a scale | Standard Error 0.266 |
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 24 | -0.45 score on a scale | Standard Error 0.298 |
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 36 | -1.23 score on a scale | Standard Error 0.305 |
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 48 | -1.21 score on a scale | Standard Error 0.317 |
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 72 | -0.79 score on a scale | Standard Error 0.352 |
| Placebo | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 96 | -0.82 score on a scale | Standard Error 0.362 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 72 | -0.58 score on a scale | Standard Error 0.309 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 12 | -0.44 score on a scale | Standard Error 0.261 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 48 | -0.99 score on a scale | Standard Error 0.295 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 24 | -0.65 score on a scale | Standard Error 0.28 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 96 | -0.75 score on a scale | Standard Error 0.306 |
| Burosumab | Change From Baseline Over Time in BFI Worst Fatigue Score | Change at Week 36 | -0.90 score on a scale | Standard Error 0.271 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 12 | -2.11 μg/L | Standard Error 1.529 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 24 | 1.03 μg/L | Standard Error 1.801 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 36 | 10.42 μg/L | Standard Error 2.017 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 48 | 6.69 μg/L | Standard Error 1.929 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 72 | -0.92 μg/L | Standard Error 1.779 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 96 | -2.49 μg/L | Standard Error 1.887 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 72 | -3.39 μg/L | Standard Error 1.739 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 12 | 6.52 μg/L | Standard Error 2.832 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 48 | 0.23 μg/L | Standard Error 1.83 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 24 | 5.70 μg/L | Standard Error 2.038 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 96 | -2.76 μg/L | Standard Error 1.64 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Bone-Specific Alkaline Phosphatase (BALP) | Change at Week 36 | 4.46 μg/L | Standard Error 1.607 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 12 | 26.96 pg/mL | Standard Error 35.689 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 24 | -4.20 pg/mL | Standard Error 34.835 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 36 | 350.89 pg/mL | Standard Error 53.131 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 48 | 310.67 pg/mL | Standard Error 45.003 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 72 | 178.03 pg/mL | Standard Error 42.702 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 96 | 79.04 pg/mL | Standard Error 45.622 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 72 | 51.59 pg/mL | Standard Error 42.863 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 12 | 322.09 pg/mL | Standard Error 56.924 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 48 | 138.61 pg/mL | Standard Error 37.886 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 24 | 184.56 pg/mL | Standard Error 39.213 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 96 | 10.84 pg/mL | Standard Error 40.761 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | Change at Week 36 | 193.50 pg/mL | Standard Error 39.461 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 48 | 85.12 ng/mL | Standard Error 11.037 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 24 | 2.95 ng/mL | Standard Error 6.423 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 72 | 48.98 ng/mL | Standard Error 7.286 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 36 | 100.00 ng/mL | Standard Error 10.562 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 96 | 22.98 ng/mL | Standard Error 7.075 |
| Placebo | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 12 | -1.86 ng/mL | Standard Error 5.958 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 96 | 12.48 ng/mL | Standard Error 8.661 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 12 | 96.22 ng/mL | Standard Error 14.264 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 36 | 49.71 ng/mL | Standard Error 6.786 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 48 | 40.07 ng/mL | Standard Error 7.292 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 72 | 18.04 ng/mL | Standard Error 9.186 |
| Burosumab | Change From Baseline Over Time in Biochemical Marker of Bone Remodeling Procollagen Type 1 N-Propeptide (P1NP) | Change at Week 24 | 63.50 ng/mL | Standard Error 7.239 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 12 | -0.29 score on a scale | Standard Error 0.215 |
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 24 | -0.28 score on a scale | Standard Error 0.242 |
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 36 | -1.30 score on a scale | Standard Error 0.26 |
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 48 | -1.28 score on a scale | Standard Error 0.251 |
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 72 | -1.22 score on a scale | Standard Error 0.247 |
| Placebo | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 96 | -1.08 score on a scale | Standard Error 0.26 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 72 | -1.24 score on a scale | Standard Error 0.263 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 12 | -0.51 score on a scale | Standard Error 0.207 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 48 | -1.04 score on a scale | Standard Error 0.235 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 24 | -0.41 score on a scale | Standard Error 0.207 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 96 | -1.43 score on a scale | Standard Error 0.234 |
| Burosumab | Change From Baseline Over Time in BPI Pain Interference Score | Change at Week 36 | -0.79 score on a scale | Standard Error 0.221 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 12 | -0.32 score on a scale | Standard Error 0.166 |
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 24 | -0.10 score on a scale | Standard Error 0.211 |
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 36 | -0.97 score on a scale | Standard Error 0.214 |
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 48 | -1.13 score on a scale | Standard Error 0.205 |
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 72 | -1.36 score on a scale | Standard Error 0.216 |
| Placebo | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 96 | -1.18 score on a scale | Standard Error 0.195 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 72 | -1.24 score on a scale | Standard Error 0.231 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 12 | -0.43 score on a scale | Standard Error 0.163 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 48 | -0.79 score on a scale | Standard Error 0.162 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 24 | -0.53 score on a scale | Standard Error 0.172 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 96 | -1.42 score on a scale | Standard Error 0.229 |
| Burosumab | Change From Baseline Over Time in BPI Pain Severity Score | Change at Week 36 | -0.62 score on a scale | Standard Error 0.184 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 12 | -0.37 score on a scale | Standard Error 0.216 |
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 24 | -0.31 score on a scale | Standard Error 0.242 |
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 36 | -1.25 score on a scale | Standard Error 0.234 |
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 48 | -1.49 score on a scale | Standard Error 0.243 |
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 72 | -1.28 score on a scale | Standard Error 0.283 |
| Placebo | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 96 | -0.99 score on a scale | Standard Error 0.265 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 72 | -1.21 score on a scale | Standard Error 0.316 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 12 | -0.62 score on a scale | Standard Error 0.208 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 48 | -1.05 score on a scale | Standard Error 0.23 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 24 | -0.77 score on a scale | Standard Error 0.228 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 96 | -1.48 score on a scale | Standard Error 0.299 |
| Burosumab | Change From Baseline Over Time in BPI Worst Pain Score | Change at Week 36 | -0.95 score on a scale | Standard Error 0.228 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 2 | -0.02 mg/dL | Standard Error 0.072 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 4 | -0.03 mg/dL | Standard Error 0.07 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 12 | 0.11 mg/dL | Standard Error 0.082 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 22 | 0.02 mg/dL | Standard Error 0.069 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 24 | 0.07 mg/dL | Standard Error 0.071 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 48 | 0.55 mg/dL | Standard Error 0.087 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 60 | 0.57 mg/dL | Standard Error 0.097 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 72 | 0.55 mg/dL | Standard Error 0.086 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 84 | 0.49 mg/dL | Standard Error 0.078 |
| Placebo | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 96 | 0.29 mg/dL | Standard Error 0.086 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 72 | 0.43 mg/dL | Standard Error 0.091 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 2 | 1.60 mg/dL | Standard Error 0.121 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 48 | 0.48 mg/dL | Standard Error 0.091 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 4 | 0.91 mg/dL | Standard Error 0.117 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 96 | 0.46 mg/dL | Standard Error 0.084 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 12 | 0.70 mg/dL | Standard Error 0.107 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 60 | 0.43 mg/dL | Standard Error 0.086 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 22 | 1.01 mg/dL | Standard Error 0.123 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 84 | 0.42 mg/dL | Standard Error 0.092 |
| Burosumab | Change From Baseline Over Time in Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate (TmP/GFR) | Change at Week 24 | 0.51 mg/dL | Standard Error 0.093 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 1 | 2.04 pg/mL | Standard Error 2.251 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 2 | 1.40 pg/mL | Standard Error 2.113 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 4 | 2.61 pg/mL | Standard Error 2.3 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 20 | 2.88 pg/mL | Standard Error 2.163 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 21 | 3.09 pg/mL | Standard Error 2.177 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 22 | 3.45 pg/mL | Standard Error 2.289 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 46 | 25.23 pg/mL | Standard Error 2.576 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 48 | 10.50 pg/mL | Standard Error 2.418 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 60 | 9.29 pg/mL | Standard Error 2.336 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 70 | 24.20 pg/mL | Standard Error 2.529 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 72 | 7.12 pg/mL | Standard Error 2.424 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 84 | 5.13 pg/mL | Standard Error 2.388 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 94 | 18.96 pg/mL | Standard Error 2.655 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 96 | 3.43 pg/mL | Standard Error 2.348 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 108 | 4.76 pg/mL | Standard Error 2.349 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 120 | 4.64 pg/mL | Standard Error 2.496 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 132 | 4.08 pg/mL | Standard Error 3.142 |
| Placebo | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 144 | -0.38 pg/mL | Standard Error 4.677 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 1 | 87.23 pg/mL | Standard Error 5.5 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 132 | 8.05 pg/mL | Standard Error 4.227 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 2 | 58.20 pg/mL | Standard Error 3.931 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 70 | 18.82 pg/mL | Standard Error 2.486 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 4 | 20.55 pg/mL | Standard Error 2.828 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 96 | 1.95 pg/mL | Standard Error 2.356 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 20 | 8.11 pg/mL | Standard Error 2.294 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 72 | 5.52 pg/mL | Standard Error 2.607 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 21 | 33.95 pg/mL | Standard Error 3.019 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 120 | 5.37 pg/mL | Standard Error 2.935 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 22 | 26.10 pg/mL | Standard Error 2.952 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 84 | 1.16 pg/mL | Standard Error 2.549 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 46 | 23.08 pg/mL | Standard Error 3.243 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 108 | 4.29 pg/mL | Standard Error 2.672 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 48 | 7.24 pg/mL | Standard Error 2.449 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 94 | 15.26 pg/mL | Standard Error 2.502 |
| Burosumab | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 60 | 5.69 pg/mL | Standard Error 2.583 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 14 | 0.02 mmol/L | Standard Error 0.022 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 2 | -0.03 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 4 | -0.03 mmol/L | Standard Error 0.022 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 6 | -0.00 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 10 | 0.01 mmol/L | Standard Error 0.022 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 12 | -0.01 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 1 | -0.01 mmol/L | Standard Error 0.024 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 18 | 0.02 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 20 | -0.01 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 21 | -0.00 mmol/L | Standard Error 0.024 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 22 | -0.02 mmol/L | Standard Error 0.022 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 24 | -0.00 mmol/L | Standard Error 0.023 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 26 | 0.47 mmol/L | Standard Error 0.035 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 28 | 0.28 mmol/L | Standard Error 0.028 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 34 | 0.36 mmol/L | Standard Error 0.029 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 36 | 0.17 mmol/L | Standard Error 0.026 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 46 | 0.31 mmol/L | Standard Error 0.026 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 48 | 0.13 mmol/L | Standard Error 0.027 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 60 | 0.14 mmol/L | Standard Error 0.028 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 70 | 0.30 mmol/L | Standard Error 0.029 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 72 | 0.13 mmol/L | Standard Error 0.025 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 84 | 0.12 mmol/L | Standard Error 0.025 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 94 | 0.25 mmol/L | Standard Error 0.029 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 96 | 0.07 mmol/L | Standard Error 0.026 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 108 | 0.11 mmol/L | Standard Error 0.028 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 120 | 0.09 mmol/L | Standard Error 0.027 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 132 | 0.12 mmol/L | Standard Error 0.033 |
| Placebo | Change From Baseline Over Time in Serum Phosphorus | Change at Week 144 | 0.05 mmol/L | Standard Error 0.064 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 1 | 0.44 mmol/L | Standard Error 0.031 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 72 | 0.11 mmol/L | Standard Error 0.027 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 2 | 0.43 mmol/L | Standard Error 0.032 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 34 | 0.28 mmol/L | Standard Error 0.031 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 4 | 0.27 mmol/L | Standard Error 0.034 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 120 | 0.13 mmol/L | Standard Error 0.033 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 6 | 0.45 mmol/L | Standard Error 0.036 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 36 | 0.13 mmol/L | Standard Error 0.027 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 10 | 0.37 mmol/L | Standard Error 0.033 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 84 | 0.14 mmol/L | Standard Error 0.027 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 12 | 0.17 mmol/L | Standard Error 0.032 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 46 | 0.27 mmol/L | Standard Error 0.03 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 14 | 0.32 mmol/L | Standard Error 0.032 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 108 | 0.13 mmol/L | Standard Error 0.031 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 18 | 0.32 mmol/L | Standard Error 0.031 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 48 | 0.11 mmol/L | Standard Error 0.027 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 20 | 0.18 mmol/L | Standard Error 0.028 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 94 | 0.30 mmol/L | Standard Error 0.029 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 21 | 0.31 mmol/L | Standard Error 0.033 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 60 | 0.11 mmol/L | Standard Error 0.028 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 22 | 0.25 mmol/L | Standard Error 0.033 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 132 | 0.15 mmol/L | Standard Error 0.036 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 24 | 0.13 mmol/L | Standard Error 0.028 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 70 | 0.30 mmol/L | Standard Error 0.03 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 26 | 0.31 mmol/L | Standard Error 0.032 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 96 | 0.13 mmol/L | Standard Error 0.025 |
| Burosumab | Change From Baseline Over Time in Serum Phosphorus | Change at Week 28 | 0.18 mmol/L | Standard Error 0.028 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 2 | -0.02 fraction of phosphate reabsorbed | Standard Error 0.013 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 4 | -0.03 fraction of phosphate reabsorbed | Standard Error 0.012 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 12 | -0.00 fraction of phosphate reabsorbed | Standard Error 0.01 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 22 | -0.01 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 24 | -0.02 fraction of phosphate reabsorbed | Standard Error 0.012 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 48 | 0.02 fraction of phosphate reabsorbed | Standard Error 0.012 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 60 | 0.03 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 72 | 0.02 fraction of phosphate reabsorbed | Standard Error 0.011 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 84 | 0.02 fraction of phosphate reabsorbed | Standard Error 0.01 |
| Placebo | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 96 | -0.01 fraction of phosphate reabsorbed | Standard Error 0.014 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 72 | 0.02 fraction of phosphate reabsorbed | Standard Error 0.011 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 2 | 0.07 fraction of phosphate reabsorbed | Standard Error 0.008 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 48 | 0.03 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 4 | 0.03 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 96 | 0.03 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 12 | 0.04 fraction of phosphate reabsorbed | Standard Error 0.008 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 60 | 0.02 fraction of phosphate reabsorbed | Standard Error 0.009 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 22 | 0.05 fraction of phosphate reabsorbed | Standard Error 0.011 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 84 | 0.01 fraction of phosphate reabsorbed | Standard Error 0.012 |
| Burosumab | Change From Baseline Over Time in Tubular Reabsorption of Phosphate (TRP) | Change at Week 24 | 0.03 fraction of phosphate reabsorbed | Standard Error 0.009 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 12 | -1.40 score on a scale | Standard Error 2.418 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 24 | 1.14 score on a scale | Standard Error 2.531 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 36 | -5.47 score on a scale | Standard Error 2.694 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 48 | -7.15 score on a scale | Standard Error 2.801 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 72 | -8.68 score on a scale | Standard Error 2.835 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 96 | -8.41 score on a scale | Standard Error 2.752 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 120 | -11.93 score on a scale | Standard Error 2.685 |
| Placebo | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 144 | -19.49 score on a scale | Standard Error 3.892 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 144 | -17.67 score on a scale | Standard Error 4.061 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 12 | -3.96 score on a scale | Standard Error 1.787 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 72 | -8.66 score on a scale | Standard Error 2.523 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 24 | -3.45 score on a scale | Standard Error 2.193 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 120 | -11.98 score on a scale | Standard Error 2.291 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 36 | -7.14 score on a scale | Standard Error 2.133 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 96 | -9.02 score on a scale | Standard Error 2.27 |
| Burosumab | Change From Baseline Over Time in WOMAC Physical Function Score | Change at Week 48 | -8.42 score on a scale | Standard Error 2.057 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 12 | -1.24 score on a scale | Standard Error 2.929 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 24 | 0.20 score on a scale | Standard Error 3.289 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 36 | -13.50 score on a scale | Standard Error 3.422 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 48 | -15.83 score on a scale | Standard Error 3.488 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 72 | -18.02 score on a scale | Standard Error 3.613 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 96 | -17.67 score on a scale | Standard Error 3.737 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 120 | -19.23 score on a scale | Standard Error 3.404 |
| Placebo | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 144 | -30.64 score on a scale | Standard Error 4.407 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 144 | -25.88 score on a scale | Standard Error 4.501 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 12 | -7.86 score on a scale | Standard Error 3.622 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 72 | -15.47 score on a scale | Standard Error 3.111 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 24 | -8.01 score on a scale | Standard Error 2.968 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 120 | -20.57 score on a scale | Standard Error 3.371 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 36 | -12.58 score on a scale | Standard Error 3.411 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 96 | -15.32 score on a scale | Standard Error 3.577 |
| Burosumab | Change From Baseline Over Time in WOMAC Stiffness Score | Change at Week 48 | -16.63 score on a scale | Standard Error 3.302 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score | -0.32 score on a scale | Standard Error 0.222 |
| Burosumab | Change From Baseline to Week 24 in Brief Pain Inventory (BPI) Question 3 (Q3; Worst Pain in Past 24 Hours) Score | -0.79 score on a scale | Standard Error 0.211 |
p-value: 0.091995% CI: [-1, 0.08]GEE model
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score | 0.46 score on a scale | Standard Error 3.139 |
| Burosumab | Change From Baseline to Week 24 in the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) Stiffness Score | -7.85 score on a scale | Standard Error 3.034 |
p-value: 0.010695% CI: [-14.68, -1.94]GEE model
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Change From Baseline to Week 24 in the WOMAC Physical Function Score | 1.79 score on a scale | Standard Error 2.722 |
| Burosumab | Change From Baseline to Week 24 in the WOMAC Physical Function Score | -3.11 score on a scale | Standard Error 2.553 |
p-value: 0.047895% CI: [-9.76, -0.05]GEE model
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo | 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 percentage of participants |
| 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 | 67.6 percentage of participants |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 percentage change | Standard Deviation 14.755 |
| Burosumab | Percent Change From Baseline in Serum Phosphorus at Each End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 35.18 percentage change | Standard Deviation 20.731 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | 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 percentage change | Standard Deviation 15.292 |
| 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 | 61.44 percentage change | Standard Deviation 28.961 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 12 | 21.91 percentage change | Standard Error 11.844 |
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 24 | 28.45 percentage change | Standard Error 15.518 |
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 36 | 18.19 percentage change | Standard Error 11.784 |
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 48 | 27.32 percentage change | Standard Error 14.328 |
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 72 | 29.53 percentage change | Standard Error 14.485 |
| Placebo | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 96 | 31.17 percentage change | Standard Error 17.248 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 72 | 25.80 percentage change | Standard Error 15.476 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 12 | 21.40 percentage change | Standard Error 11.453 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 48 | 37.50 percentage change | Standard Error 14.687 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 24 | 20.35 percentage change | Standard Error 11.567 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 96 | 30.64 percentage change | Standard Error 10.42 |
| Burosumab | Percent Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Change at Week 36 | 28.31 percentage change | Standard Error 12.173 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 12 | 7.85 percentage change | Standard Error 9.867 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 24 | 27.56 percentage change | Standard Error 10.339 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 36 | 64.41 percentage change | Standard Error 11.669 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 48 | 50.65 percentage change | Standard Error 11.317 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 72 | 19.79 percentage change | Standard Error 11.755 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 96 | 16.46 percentage change | Standard Error 11.027 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 72 | 14.40 percentage change | Standard Error 11.618 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 12 | 30.29 percentage change | Standard Error 13.476 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 48 | 23.46 percentage change | Standard Error 10.041 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 24 | 39.13 percentage change | Standard Error 10.902 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 96 | 21.21 percentage change | Standard Error 9.688 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling BALP | Change at Week 36 | 43.13 percentage change | Standard Error 11.473 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 12 | 9.64 percentage change | Standard Error 5.671 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 24 | 4.75 percentage change | Standard Error 5.28 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 36 | 61.31 percentage change | Standard Error 10.653 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 48 | 50.35 percentage change | Standard Error 6.464 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 72 | 34.78 percentage change | Standard Error 7.007 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 96 | 27.38 percentage change | Standard Error 7.783 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 72 | 17.09 percentage change | Standard Error 5.957 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 12 | 45.40 percentage change | Standard Error 7.267 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 48 | 28.33 percentage change | Standard Error 5.354 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 24 | 32.48 percentage change | Standard Error 6.414 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 96 | 13.47 percentage change | Standard Error 5.952 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling CTx | Change at Week 36 | 34.07 percentage change | Standard Error 6.25 |
Secondary
Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP
Time frame: Baseline, Weeks 12, 24, 36, 48, 72, 96
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 12 | 2.30 percentage change | Standard Error 6.318 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 24 | 7.83 percentage change | Standard Error 7.076 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 36 | 116.39 percentage change | Standard Error 9.726 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change a Week 48 | 99.10 percentage change | Standard Error 11.442 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 72 | 72.56 percentage change | Standard Error 10.055 |
| Placebo | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 96 | 41.62 percentage change | Standard Error 8.163 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 72 | 38.82 percentage change | Standard Error 10.225 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 12 | 91.78 percentage change | Standard Error 10.787 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change a Week 48 | 56.51 percentage change | Standard Error 8.771 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 24 | 72.43 percentage change | Standard Error 8.519 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 96 | 31.04 percentage change | Standard Error 8.126 |
| Burosumab | Percent Change From Baseline Over Time in Biochemical Marker of Bone Remodeling P1NP | Change at Week 36 | 63.58 percentage change | Standard Error 8.562 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 1 | 10.45 percentage change | Standard Error 13.041 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 2 | 10.53 percentage change | Standard Error 12.76 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 4 | 16.07 percentage change | Standard Error 12.81 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 20 | 21.36 percentage change | Standard Error 12.424 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 21 | 21.51 percentage change | Standard Error 12.825 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 22 | 21.07 percentage change | Standard Error 12.725 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 46 | 130.29 percentage change | Standard Error 22.718 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 48 | 70.09 percentage change | Standard Error 17.114 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 60 | 65.46 percentage change | Standard Error 13.083 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 70 | 123.58 percentage change | Standard Error 17.315 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 72 | 58.45 percentage change | Standard Error 13.957 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 84 | 55.67 percentage change | Standard Error 15.323 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 94 | 111.25 percentage change | Standard Error 21.97 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 96 | 50.17 percentage change | Standard Error 18.857 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 108 | 44.78 percentage change | Standard Error 14.219 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 120 | 58.37 percentage change | Standard Error 19.621 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 132 | 67.59 percentage change | Standard Error 35.77 |
| Placebo | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 144 | 22.65 percentage change | Standard Error 19.297 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 1 | 310.72 percentage change | Standard Error 23.225 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 132 | 42.55 percentage change | Standard Error 15.925 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 2 | 207.90 percentage change | Standard Error 16.728 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 70 | 82.03 percentage change | Standard Error 12.604 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 4 | 76.22 percentage change | Standard Error 12.147 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 96 | 22.15 percentage change | Standard Error 10.487 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 20 | 41.08 percentage change | Standard Error 11.943 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 72 | 31.14 percentage change | Standard Error 13.07 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 21 | 131.76 percentage change | Standard Error 14.862 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 120 | 36.09 percentage change | Standard Error 13.089 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 22 | 102.81 percentage change | Standard Error 14.619 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 84 | 18.83 percentage change | Standard Error 12.801 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 46 | 96.63 percentage change | Standard Error 16.909 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 108 | 29.16 percentage change | Standard Error 13.326 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 48 | 34.47 percentage change | Standard Error 12.903 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 94 | 71.30 percentage change | Standard Error 12.28 |
| Burosumab | Percent Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 60 | 32.32 percentage change | Standard Error 12.23 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 14 | 3.58 percentage change | Standard Error 3.691 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 2 | -5.91 percentage change | Standard Error 3.969 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 4 | -4.84 percentage change | Standard Error 3.792 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 6 | -0.41 percentage change | Standard Error 3.951 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 10 | 2.40 percentage change | Standard Error 3.68 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 12 | -2.14 percentage change | Standard Error 3.798 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 1 | -1.11 percentage change | Standard Error 3.936 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 18 | 3.93 percentage change | Standard Error 3.857 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 20 | -1.81 percentage change | Standard Error 3.759 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 21 | 0.21 percentage change | Standard Error 4.011 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 22 | -3.42 percentage change | Standard Error 3.709 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 24 | -0.61 percentage change | Standard Error 3.802 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 26 | 78.30 percentage change | Standard Error 5.993 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 28 | 46.07 percentage change | Standard Error 4.766 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 34 | 59.18 percentage change | Standard Error 4.959 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 36 | 28.03 percentage change | Standard Error 4.424 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 46 | 51.49 percentage change | Standard Error 4.38 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 48 | 21.58 percentage change | Standard Error 4.365 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 60 | 22.90 percentage change | Standard Error 4.338 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 70 | 50.22 percentage change | Standard Error 4.916 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 72 | 21.59 percentage change | Standard Error 4.155 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 84 | 21.47 percentage change | Standard Error 4.089 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 94 | 43.67 percentage change | Standard Error 4.834 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 96 | 12.97 percentage change | Standard Error 4.216 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 108 | 19.21 percentage change | Standard Error 4.665 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 120 | 15.13 percentage change | Standard Error 4.365 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 132 | 20.43 percentage change | Standard Error 5.362 |
| Placebo | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 144 | 5.49 percentage change | Standard Error 12.212 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 1 | 69.24 percentage change | Standard Error 4.762 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 72 | 19.45 percentage change | Standard Error 4.344 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 2 | 69.39 percentage change | Standard Error 4.881 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 34 | 45.83 percentage change | Standard Error 4.871 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 4 | 42.89 percentage change | Standard Error 5.325 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 120 | 21.50 percentage change | Standard Error 5.268 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 6 | 72.96 percentage change | Standard Error 5.944 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 36 | 22.34 percentage change | Standard Error 4.256 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 10 | 59.96 percentage change | Standard Error 5.356 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 84 | 23.58 percentage change | Standard Error 4.2 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 12 | 29.50 percentage change | Standard Error 5.087 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 46 | 45.39 percentage change | Standard Error 5.018 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 14 | 52.14 percentage change | Standard Error 5.194 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 108 | 23.39 percentage change | Standard Error 4.749 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 18 | 53.22 percentage change | Standard Error 5.106 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 48 | 19.12 percentage change | Standard Error 4.19 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 20 | 31.28 percentage change | Standard Error 4.472 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 94 | 49.36 percentage change | Standard Error 4.501 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 21 | 50.59 percentage change | Standard Error 5.123 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 60 | 19.60 percentage change | Standard Error 4.436 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 22 | 40.98 percentage change | Standard Error 5.196 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 132 | 25.34 percentage change | Standard Error 5.847 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 24 | 22.01 percentage change | Standard Error 4.523 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 70 | 47.81 percentage change | Standard Error 4.768 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 26 | 51.51 percentage change | Standard Error 5.204 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 96 | 21.65 percentage change | Standard Error 3.854 |
| Burosumab | Percent Change From Baseline Over Time in Serum Phosphorus | Change at Week 28 | 31.32 percentage change | Standard Error 4.415 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 2 | -2.15 percentage change | Standard Error 4.515 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 4 | -2.73 percentage change | Standard Error 4.416 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 12 | 6.28 percentage change | Standard Error 4.9 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 22 | 1.38 percentage change | Standard Error 4.252 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 24 | 3.63 percentage change | Standard Error 4.46 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 48 | 35.52 percentage change | Standard Error 5.39 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 60 | 37.13 percentage change | Standard Error 5.855 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 72 | 35.89 percentage change | Standard Error 5.492 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 84 | 33.15 percentage change | Standard Error 4.924 |
| Placebo | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 96 | 19.95 percentage change | Standard Error 5.417 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 72 | 28.98 percentage change | Standard Error 5.513 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 2 | 100.10 percentage change | Standard Error 7.222 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 48 | 31.02 percentage change | Standard Error 5.489 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 4 | 56.53 percentage change | Standard Error 6.816 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 96 | 29.67 percentage change | Standard Error 4.759 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 12 | 43.65 percentage change | Standard Error 6.206 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 60 | 27.49 percentage change | Standard Error 5.002 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 22 | 62.38 percentage change | Standard Error 7.144 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 84 | 27.69 percentage change | Standard Error 5.527 |
| Burosumab | Percent Change From Baseline Over Time in TmP/GFR | Change at Week 24 | 33.02 percentage change | Standard Error 5.464 |
Secondary
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
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period. Participants with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 2 | -2.00 percentage change | Standard Error 1.53 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 4 | -3.75 percentage change | Standard Error 1.486 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 12 | 0.56 percentage change | Standard Error 1.261 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 22 | -0.01 percentage change | Standard Error 1.163 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 24 | -1.56 percentage change | Standard Error 1.579 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 48 | 3.95 percentage change | Standard Error 1.547 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 60 | 3.99 percentage change | Standard Error 1.096 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 72 | 3.90 percentage change | Standard Error 1.427 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 84 | 3.78 percentage change | Standard Error 1.276 |
| Placebo | Percent Change From Baseline Over Time in TRP | Change at Week 96 | -0.09 percentage change | Standard Error 1.582 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 72 | 3.24 percentage change | Standard Error 1.414 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 2 | 9.81 percentage change | Standard Error 1.111 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 48 | 4.70 percentage change | Standard Error 1.183 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 4 | 4.86 percentage change | Standard Error 1.114 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 96 | 4.44 percentage change | Standard Error 1.116 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 12 | 5.45 percentage change | Standard Error 1.079 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 60 | 3.00 percentage change | Standard Error 1.123 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 22 | 7.03 percentage change | Standard Error 1.451 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 84 | 1.97 percentage change | Standard Error 1.516 |
| Burosumab | Percent Change From Baseline Over Time in TRP | Change at Week 24 | 4.21 percentage change | Standard Error 1.141 |
Secondary
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
Time frame: Baseline through Week 24
Population: Primary Analysis Set: all randomized participants who received at least 1 dose of study drug during the Placebo-Controlled Treatment Period.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | 2.08 mg/dL | Standard Deviation 0.292 |
| Burosumab | Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | 3.08 mg/dL | Standard Deviation 0.477 |