X-linked Hypophosphatemia
Conditions
Keywords
KRN23, Fibroblast growth factor 23 (FGF23), XLH, X-linked Hypophosphatemia
Brief summary
The primary objective of this study is to establish the effect of KRN23 treatment on improvement in XLH-associated osteomalacia as determined by osteoid volume (osteoid volume/bone volume, OV/BV).
Interventions
BIOLOGICALburosumab
solution for subcutaneous injection
Sponsors
Kyowa Kirin Co., Ltd.
Kyowa Kirin, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
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 homology to endopeptidases located on the X chromosome (PHEX) PHEX mutation in either the patient or in 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 based on overnight fasting (min. 8 hours): * Serum phosphorus \< 2.5 mg/dL at Screening * Ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) \< 2.5 mg/dL at Screening 4. Presence of skeletal pain attributed to XLH/osteomalacia, as defined by a score of ≥ 4 on the Brief Pain Inventory question 3 (BPI-Q3, Worst Pain) at Screening. (Skeletal pain that, in the opinion of the investigator, is attributed solely to causes other than XLH/osteomalacia-for example, back pain 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 estimated glomerular filtration rate (eGFR) eGFR of 45 to \<60 mL/min at Screening with confirmation that the renal insufficiency is not due to nephrocalcinosis 6. Provide written informed consent after the nature of the study has been explained, and prior to any research-related procedures. If the subject in a minor, provide written assent 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 7. Willing to provide access to prior medical records for the collection of biochemical and radiographic data and disease history 8. 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. 9. Participants of child-bearing potential or with partners of child-bearing potential who have not undergone a total hysterectomy or a bilateral salpingo-oophorectomy and are sexually active must consent to use two effective methods 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 10. 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
Exclusion criteria
1. Use of any pharmacologic vitamin D metabolite or analog (e.g. calcitriol, doxercalciferol, and paricalcitol) within the 2 years before Screening 2. Use of oral phosphate within 2 years before Screening 3. Use of aluminum hydroxide antacids, acetazolamides, and thiazides within 7 days prior to Screening 4. Use of bisphosphonates in the 2 years prior to Screening 5. Use of denosumab in the 6 months prior to Screening 6. Use of teriparatide in the 2 months prior to Screening 7. Chronic use of systemic corticosteroids defined as more than 10 days in the 2 months prior to Screening 8. Corrected serum calcium level ≥ 10.8 mg/dL (2.7 mmol/L) at Screening 9. Serum intact parathyroid hormone (iPTH) ≥ 2.5 times the upper limit of normal (ULN) at Screening 10. Use of medication to suppress parathyroid hormone (PTH) (cinacalcet for example) within 60 days prior to Screening 11. Prothrombin time/Partial thromboplastin time (PT/PTT) outside the normal range at Screening 12. Evidence of any disease or use of anticoagulant medication (such as warfarin, heparin, direct thrombin inhibitors, or Xa inhibitors (xabans) that, in the opinion of the investigator, cannot be discontinued) that may increase the risk of bleeding during the biopsy procedure 13. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study 14. Unable or unwilling to withhold prohibited medications throughout the study 15. Documented dependence on narcotics 16. Use of KRN23, or any other therapeutic monoclonal antibody within 90 days prior to Screening 17. Use of investigational product or investigational medical device within 30 days prior to Screening, 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. 18. 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 19. History of allergic reaction or adverse reactions to tetracycline or demeclocycline 20. Prior history of positive test for human immunodeficiency virus antibody, hepatitis B surface antigen, and/or hepatitis C antibody 21. History of recurrent infection (other than dental abscesses, which are known to be associated with XLH) or predisposition to infection, or of known immunodeficiency 22. Presence of malignant neoplasm (except basal cell carcinoma) 23. Presence of a concurrent disease or condition that would interfere with study participation or affect safety 24. 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 | Description |
|---|---|---|
| Percent Change From Baseline in OV/BV at Week 48 | Baseline, 48 weeks | OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change From Baseline in O.Th at Week 48 | Baseline, 48 weeks | O.Th: mean thickness, given in micrometers, for osteoid seams. |
| Percent Change From Baseline in OS/BS at Week 48 | Baseline, 48 weeks | OS/Bs: percent of bone surface covered in osteoid. |
| Percent Change From Baseline in MLt at Week 48 | Baseline, 48 weeks | MLt: average time interval between osteoid formation and its subsequent mineralization; calculated by dividing the osteoid thickness by the adjusted apposition rate (O.Th/Aj.AR). Aj.AR; amount of new bone created (bone formation rate over the entire osteoid surface). Based on imputed MLt values. |
| Change From Baseline in MAR at Week 48 | Baseline, 48 weeks | MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them. |
| Change From Baseline in MS/BS at Week 48 | Baseline, 48 weeks | MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface (\[dLS + sLS/2\]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. |
| Change From Baseline in BFR/BS at Week 48 | Baseline, 48 weeks | BFR/BS: amount of new bone formed in unit time per unit of bone surface; calculated by multiplying MS/BS by the MAR. MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface (\[dLS + sLS/2\]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them. |
| Change From Baseline in BFR/OS at Week 48 | Baseline, 48 weeks | BFR/OS: bone formation rate to osteoid surface ratio, related to the Aj.AR (amount of new bone created \[bone formation rate over the entire osteoid surface\]). |
| Change From Baseline in BFR/BV at Week 48 | Baseline, 48 weeks | BFR/BV: equivalent to bone turnover rate. |
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle Between Baseline and Week 24 | Baseline, up to 24 weeks | The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% CI was calculated using Wilson score method. |
| Mean Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | Baseline, up to 24 weeks | — |
| Percent Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | Baseline, up to 24 weeks | — |
| Mean Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | Baseline, up to 24 weeks | — |
| Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 | Baseline, up to 24 weeks | The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% confidence interval (CI) was calculated using Wilson score method. |
| Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | Baseline, up to 24 weeks | — |
| Change From Baseline Over Time in Serum 1,25(OH)2D | Baseline, Week 1, Week 2, Week 4, Week 20, Week 21, Week 22, Week 24, Week 48, Week 60, Week 70, Week 72, Week 84, Week 94, Week 96, Week 108, Week 120, Week 132 | — |
| Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Baseline, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96, End of Study II (EOSII) (up to Week 141) | — |
| Change From Baseline Over Time in TmP/GFR | Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141) | TmP/GFR: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate. |
| Change From Baseline Over Time in TRP | Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141) | TRP: tubular reabsorption of phosphate. |
| Change From Baseline Over Time in P1NP | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | P1NP: procollagen type 1 N-propeptide. |
| Percent Change From Baseline Over Time in P1NP | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | — |
| Change From Baseline Over Time in CTx | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | CTx: carboxy-terminal cross-linked telopeptide of type I collagen. |
| Percent Change From Baseline Over Time in CTx | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | CTx: carboxy-terminal cross-linked telopeptide of type I collagen. |
| Change From Baseline Over Time in BALP | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | BALP: bone-specific alkaline phosphatase. |
| Percent Change From Baseline Over Time in BALP | Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141) | BALP: bone-specific alkaline phosphatase. |
| Percentage Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | Baseline, up to 24 weeks | — |
Countries
Canada, Denmark, France, Japan, South Korea, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Open-Label Burosumab Q4W 1.0 mg/kg Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg. | 14 |
| Total | 14 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Open-Label Period (Week 0 to Week 48) | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Open-Label Burosumab Q4W |
|---|---|
| 1,25(OH) 2D | 37.25 pg/mL STANDARD_DEVIATION 11.686 |
| 24-Hour Urinary Phosphorus | 0.82 g/24hr STANDARD_DEVIATION 0.237 |
| Age, Continuous | 40.13 years STANDARD_DEVIATION 8.725 |
| Bone Formation Rate/Bone Surface (BFR/BS) | 26.68 µm^3/µm^2/year STANDARD_DEVIATION 19.48 |
| Bone Formation Rate/Bone Volume (BFR/BV) | 38.33 percent/year STANDARD_DEVIATION 37.173 |
| Bone Formation Rate/Osteoblast Surface (BFR/OS) | 2309.00 µm^3/µm^2/year STANDARD_DEVIATION 2941.97 |
| Bone-Specific Alkaline Phosphatase (BALP) | 20.43 μg/L STANDARD_DEVIATION 9.288 |
| Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx-I) | 646.93 pg/mL STANDARD_DEVIATION 401.641 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mineral Apposition Rate (MAR) | 0.58 µm/day STANDARD_DEVIATION 0.448 |
| Mineralization Lag Time (MLt) | 1539.81 days STANDARD_DEVIATION 1587.086 |
| Mineralizing Surface/Bone Surface (MS/BS) | 5.99 percentage of mineralizing surface STANDARD_DEVIATION 4.763 |
| Mineralizing Surface/OsteoidSurface (MS/OS) | 6.47 percentage of mineralizing surface STANDARD_DEVIATION 5.12 |
| Osteoid Surface/Bone Surface (OS/BS) | 91.73 percentage of osteoid surface STANDARD_DEVIATION 3.438 |
| Osteoid Thickness (O.Th) | 17.21 µm STANDARD_DEVIATION 4.105 |
| Osteoid Volume/Bone Volume (OV/BV) | 26.12 percentage of osteoid volume STANDARD_DEVIATION 12.357 |
| Procollagen Type 1 N-Propeptide (P1NP) | 77.00 ng/mL STANDARD_DEVIATION 33.273 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 9 Participants |
| Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR) | 1.87 mg/dL STANDARD_DEVIATION 0.307 |
| Serum Phosphorus | 2.24 mg/dL STANDARD_DEVIATION 0.396 |
| Sex: Female, Male Female | 8 Participants |
| Sex: Female, Male Male | 6 Participants |
| Tubular Reabsorption of Phosphate (TRP) | 0.84 fraction of phosphorus reabsorbed STANDARD_DEVIATION 0.048 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 14 |
| other Total, other adverse events | 14 / 14 |
| serious Total, serious adverse events | 4 / 14 |
Outcome results
Primary
Percent Change From Baseline in OV/BV at Week 48
OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline in OV/BV at Week 48 | -54.18 percentage change of unmineralized bone | Standard Deviation 20.211 |
p-value: <0.000195% CI: [-68.64, -39.72]t-test
Secondary
Change From Baseline in BFR/BS at Week 48
BFR/BS: amount of new bone formed in unit time per unit of bone surface; calculated by multiplying MS/BS by the MAR. MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface (\[dLS + sLS/2\]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline in BFR/BS at Week 48 | -4.90 µm^3/µm^2/year | Standard Deviation 27.356 |
Secondary
Change From Baseline in BFR/BV at Week 48
BFR/BV: equivalent to bone turnover rate.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline in BFR/BV at Week 48 | -13.50 percentage of bone turnover/year | Standard Deviation 32.904 |
Secondary
Change From Baseline in BFR/OS at Week 48
BFR/OS: bone formation rate to osteoid surface ratio, related to the Aj.AR (amount of new bone created \[bone formation rate over the entire osteoid surface\]).
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline in BFR/OS at Week 48 | -1557.25 µm^3/µm^2/year | Standard Deviation 3139.075 |
Secondary
Change From Baseline in MAR at Week 48
MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline in MAR at Week 48 | 0.04 µm/day | Standard Deviation 0.506 |
Secondary
Change From Baseline in MS/BS at Week 48
MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface (\[dLS + sLS/2\]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline in MS/BS at Week 48 | 1.32 percent of mineralizing surface | Standard Deviation 4.365 |
Secondary
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Time frame: Baseline, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96, End of Study II (EOSII) (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 12 | 0.10 g/24 hours | Standard Error 0.128 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 24 | -0.04 g/24 hours | Standard Error 0.075 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 36 | -0.01 g/24 hours | Standard Error 0.059 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 48 | -0.04 g/24 hours | Standard Error 0.076 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 72 | 0.00 g/24 hours | Standard Error 0.096 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | Week 96 | -0.13 g/24 hours | Standard Error 0.082 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in 24-Hour Urinary Phosphorus | EOSII | -0.07 g/24 hours | Standard Error 0.171 |
Comparison: Week 1295% CI: [-0.15, 0.35]
Comparison: Week 2495% CI: [-0.19, 0.11]
Comparison: Week 3695% CI: [-0.12, 0.11]
Comparison: Week 48p-value: 0.602195% CI: [-0.19, 0.11]GEE model
Comparison: Week 7295% CI: [-0.19, 0.19]
Comparison: Week 9695% CI: [-0.29, 0.03]
Comparison: EOS II95% CI: [-0.41, 0.26]
Secondary
Change From Baseline Over Time in BALP
BALP: bone-specific alkaline phosphatase.
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | Week 12 | 10.93 μg/L | Standard Error 3.547 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | Week 24 | 5.82 μg/L | Standard Error 2.98 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | Week 48 | 4.50 μg/L | Standard Error 3.99 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | Week 72 | 3.13 μg/L | Standard Error 2.435 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | Week 96 | 1.14 μg/L | Standard Error 2.028 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in BALP | EOSII | -5.80 μg/L | Standard Error 3.396 |
Comparison: Week 1295% CI: [3.98, 17.89]
Comparison: Week 2495% CI: [-0.02, 11.66]
Comparison: Week 48p-value: 0.259295% CI: [-3.32, 12.32]GEE model
Comparison: Week 7295% CI: [-1.64, 7.9]
Comparison: Week 9695% CI: [-2.84, 5.11]
Comparison: EOSII95% CI: [-12.46, 0.85]
Secondary
Change From Baseline Over Time in CTx
CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | Week 12 | 464.84 pg/mL | Standard Error 61.696 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | Week 24 | 404.13 pg/mL | Standard Error 55.948 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | Week 48 | 175.13 pg/mL | Standard Error 44.022 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | Week 72 | 143.11 pg/mL | Standard Error 92.503 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | Week 96 | 76.80 pg/mL | Standard Error 57.357 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in CTx | EOSII | -41.32 pg/mL | Standard Error 83.144 |
Comparison: Week 1295% CI: [343.92, 585.77]
Comparison: Week 2495% CI: [294.47, 513.78]
Comparison: Week 48p-value: <0.000195% CI: [88.85, 261.41]GEE model
Comparison: Week 7295% CI: [-38.2, 324.41]
Comparison: Week 9695% CI: [-35.62, 189.22]
Comparison: EOSII95% CI: [-204.28, 121.64]
Secondary
Change From Baseline Over Time in P1NP
P1NP: procollagen type 1 N-propeptide.
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | Week 12 | 99.18 ng/mL | Standard Error 11.403 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | Week 24 | 104.33 ng/mL | Standard Error 11.153 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | Week 48 | 52.49 ng/mL | Standard Error 11.554 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | Week 72 | 37.29 ng/mL | Standard Error 12.294 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | Week 96 | 29.29 ng/mL | Standard Error 13.321 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in P1NP | EOSII | 2.14 ng/mL | Standard Error 10.105 |
Comparison: Week 1295% CI: [76.83, 121.53]
Comparison: Week 2495% CI: [82.47, 126.19]
Comparison: Week 48p-value: <0.000195% CI: [29.84, 75.13]GEE model
Comparison: Week 7295% CI: [13.19, 61.38]
Comparison: Week 9695% CI: [3.18, 55.4]
Comparison: EOSII95% CI: [-17.67, 21.94]
Secondary
Change From Baseline Over Time in Serum 1,25(OH)2D
Time frame: Baseline, Week 1, Week 2, Week 4, Week 20, Week 21, Week 22, Week 24, Week 48, Week 60, Week 70, Week 72, Week 84, Week 94, Week 96, Week 108, Week 120, Week 132
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 1 | 107.75 pg/mL | Standard Error 15.964 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 2 | 48.41 pg/mL | Standard Error 7.397 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 4 | 13.58 pg/mL | Standard Error 3.435 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 20 | -1.34 pg/mL | Standard Error 3.617 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 21 | 31.75 pg/mL | Standard Error 5.233 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 22 | 11.50 pg/mL | Standard Error 4.06 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 24 | -3.04 pg/mL | Standard Error 4.891 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 48 | -1.72 pg/mL | Standard Error 4.19 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 60 | -5.73 pg/mL | Standard Error 3.395 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 70 | 3.36 pg/mL | Standard Error 3.987 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 72 | -5.55 pg/mL | Standard Error 2.895 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 84 | -5.55 pg/mL | Standard Error 2.962 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 94 | 9.63 pg/mL | Standard Error 4.239 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 96 | -6.09 pg/mL | Standard Error 2.403 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 108 | 0.02 pg/mL | Standard Error 4.714 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 120 | 1.45 pg/mL | Standard Error 4.197 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in Serum 1,25(OH)2D | Week 132 | -1.69 pg/mL | Standard Error 1.993 |
Comparison: Week 195% CI: [76.46, 139.03]
Comparison: Week 295% CI: [33.91, 62.91]
Comparison: Week 495% CI: [6.85, 20.31]
Comparison: Week 2095% CI: [-8.43, 5.75]
Comparison: Week 2195% CI: [21.49, 42]
Comparison: Week 2295% CI: [3.54, 19.46]
Comparison: Week 2495% CI: [-12.62, 6.55]
Comparison: Week 48p-value: 0.682195% CI: [-9.93, 6.5]GEE model
Comparison: Week 6095% CI: [-12.38, 0.92]
Comparison: Week 7095% CI: [-4.45, 11.18]
Comparison: Week 7295% CI: [-11.22, 0.13]
Comparison: Week 8495% CI: [-11.35, 0.26]
Comparison: Week 9495% CI: [1.33, 17.94]
Comparison: Week 9695% CI: [-10.8, -1.38]
Comparison: Week 10895% CI: [-9.22, 9.26]
Comparison: Week 12095% CI: [-6.77, 9.68]
Comparison: Week 13295% CI: [-5.6, 2.21]
Secondary
Change From Baseline Over Time in TmP/GFR
TmP/GFR: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate.
Time frame: Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 2 | 1.76 mg/dL | Standard Error 0.136 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 4 | 0.78 mg/dL | Standard Error 0.097 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 12 | 0.58 mg/dL | Standard Error 0.122 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 22 | 0.87 mg/dL | Standard Error 0.064 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 24 | 0.44 mg/dL | Standard Error 0.101 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 48 | 0.20 mg/dL | Standard Error 0.097 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 60 | 0.30 mg/dL | Standard Error 0.171 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 72 | 0.28 mg/dL | Standard Error 0.127 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 84 | 0.39 mg/dL | Standard Error 0.136 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | Week 96 | 0.29 mg/dL | Standard Error 0.097 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TmP/GFR | EOSII | 0.21 mg/dL | Standard Error 0.068 |
Comparison: Week 295% CI: [1.49, 2.03]
Comparison: Week 495% CI: [0.59, 0.97]
Comparison: Week 1295% CI: [0.34, 0.82]
Comparison: Week 2295% CI: [0.74, 0.99]
Comparison: Week 2495% CI: [0.24, 0.64]
Comparison: Week 48p-value: 0.04395% CI: [0.01, 0.38]GEE model
Comparison: Week 6095% CI: [-0.04, 0.64]
Comparison: Week 7295% CI: [0.03, 0.52]
Comparison: Week 8495% CI: [0.13, 0.66]
Comparison: Week 9695% CI: [0.1, 0.48]
Comparison: EOSII95% CI: [0.08, 0.34]
Secondary
Change From Baseline Over Time in TRP
TRP: tubular reabsorption of phosphate.
Time frame: Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 2 | 0.07 fraction of phosphorus reabsorbed | Standard Error 0.005 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 4 | 0.03 fraction of phosphorus reabsorbed | Standard Error 0.013 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 12 | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.013 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 22 | 0.04 fraction of phosphorus reabsorbed | Standard Error 0.007 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 24 | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.015 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 48 | -0.00 fraction of phosphorus reabsorbed | Standard Error 0.021 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 60 | 0.03 fraction of phosphorus reabsorbed | Standard Error 0.016 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 72 | -0.02 fraction of phosphorus reabsorbed | Standard Error 0.035 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 84 | 0.02 fraction of phosphorus reabsorbed | Standard Error 0.019 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | Week 96 | 0.02 fraction of phosphorus reabsorbed | Standard Error 0.014 |
| Open-Label Burosumab Q4W | Change From Baseline Over Time in TRP | EOSII | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.011 |
Comparison: Week 8495% CI: [-0.01, 0.06]
Comparison: Week 295% CI: [0.06, 0.08]
Comparison: Week 495% CI: [0.01, 0.06]
Comparison: Week 1295% CI: [-0.01, 0.04]
Comparison: Week 2295% CI: [0.02, 0.05]
Comparison: Week 2495% CI: [-0.02, 0.04]
Comparison: Week 48p-value: 0.837795% CI: [-0.05, 0.04]GEE model
Comparison: Week 6095% CI: [0, 0.06]
Comparison: Week 7295% CI: [-0.09, 0.05]
Comparison: Week 9695% CI: [-0.01, 0.05]
Comparison: EOSII95% CI: [-0.01, 0.03]
Secondary
Mean Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Mean Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 0.46 mg/dL | Standard Deviation 0.303 |
Secondary
Mean Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Mean Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 1.07 mg/dL | Standard Deviation 0.3 |
Secondary
Percentage Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percentage Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 23.32 percent change of serum phosphorus level | Standard Deviation 19.836 |
Secondary
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle Between Baseline and Week 24
The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% CI was calculated using Wilson score method.
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-Label Burosumab Q4W | Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle Between Baseline and Week 24 | 78.6 percentage of participants |
Secondary
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% confidence interval (CI) was calculated using Wilson score method.
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-Label Burosumab Q4W | Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24 | 92.9 percentage of participants |
p-value: <0.0001binomial test
Secondary
Percent Change From Baseline in MLt at Week 48
MLt: average time interval between osteoid formation and its subsequent mineralization; calculated by dividing the osteoid thickness by the adjusted apposition rate (O.Th/Aj.AR). Aj.AR; amount of new bone created (bone formation rate over the entire osteoid surface). Based on imputed MLt values.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline in MLt at Week 48 | -52.24 percent change in average time interval | Standard Deviation 58.487 |
p-value: 0.019995% CI: [-94.08, -10.41]t-test
Secondary
Percent Change From Baseline in OS/BS at Week 48
OS/Bs: percent of bone surface covered in osteoid.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline in OS/BS at Week 48 | -26.00 percent change of bone surface covered | Standard Deviation 15.012 |
p-value: 0.000295% CI: [-36.08, -15.91]t-test
Secondary
Percent Change From Baseline in O.Th at Week 48
O.Th: mean thickness, given in micrometers, for osteoid seams.
Time frame: Baseline, 48 weeks
Population: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline in O.Th at Week 48 | -32.21 percentage change in thickness | Standard Deviation 11.966 |
p-value: <0.000195% CI: [-40.25, -24.17]t-test
Secondary
Percent Change From Baseline Over Time in BALP
BALP: bone-specific alkaline phosphatase.
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | Week 12 | 52.54 percent change in BALP | Standard Error 15.999 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | Week 24 | 31.37 percent change in BALP | Standard Error 11.808 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | Week 48 | 24.35 percent change in BALP | Standard Error 17.63 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | EOSII | -27.30 percent change in BALP | Standard Error 12.767 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | Week 72 | 15.13 percent change in BALP | Standard Error 13.431 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in BALP | Week 96 | 6.92 percent change in BALP | Standard Error 10.387 |
Comparison: Week 1295% CI: [21.18, 83.9]
Comparison: Week 2495% CI: [8.23, 54.51]
Comparison: Week 48p-value: 0.167295% CI: [-10.2, 58.9]GEE model
Comparison: Week 7295% CI: [-11.19, 41.46]
Comparison: Week 9695% CI: [-13.44, 27.28]
Comparison: EOSII95% CI: [-52.33, -2.28]
Secondary
Percent Change From Baseline Over Time in CTx
CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | Week 12 | 89.68 percent change in CTx | Standard Error 13.316 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | Week 24 | 70.17 percent change in CTx | Standard Error 10.341 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | Week 48 | 35.86 percent change in CTx | Standard Error 7.396 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | Week 72 | 34.00 percent change in CTx | Standard Error 14.016 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | Week 96 | 25.86 percent change in CTx | Standard Error 8.461 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in CTx | EOSII | 17.88 percent change in CTx | Standard Error 9.284 |
Comparison: Week 1295% CI: [63.58, 115.78]
Comparison: Week 2495% CI: [49.9, 90.44]
Comparison: Week 48p-value: <0.000195% CI: [21.37, 50.36]GEE model
Comparison: Week 7295% CI: [6.53, 61.47]
Comparison: Week 9695% CI: [9.27, 42.44]
Comparison: EOSII95% CI: [-0.32, 36.07]
Secondary
Percent Change From Baseline Over Time in P1NP
Time frame: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | Week 12 | 133.08 percent change in P1NP | Standard Error 13.68 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | Week 24 | 137.80 percent change in P1NP | Standard Error 15.741 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | Week 48 | 76.86 percent change in P1NP | Standard Error 14.114 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | Week 72 | 50.46 percent change in P1NP | Standard Error 13.659 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | Week 96 | 41.36 percent change in P1NP | Standard Error 11.566 |
| Open-Label Burosumab Q4W | Percent Change From Baseline Over Time in P1NP | EOSII | 26.20 percent change in P1NP | Standard Error 9.919 |
Comparison: Week 1295% CI: [106.26, 159.89]
Comparison: Week 2495% CI: [106.95, 168.65]
Comparison: Week 48p-value: <0.000195% CI: [49.2, 104.53]GEE model
Comparison: Week 7295% CI: [23.69, 77.23]
Comparison: Week 9695% CI: [18.69, 64.03]
Comparison: EOSII95% CI: [6.76, 45.64]
Secondary
Percent Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Percent Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24 | 50.39 percent change of serum phosphorus level | Standard Deviation 19.942 |
Secondary
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
Time frame: Baseline, up to 24 weeks
Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Open-Label Burosumab Q4W | Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24 | 3.023 mg/dL | Standard Deviation 0.2716 |