X-Linked Hypophosphatemia
Conditions
Keywords
XLH, FGF23, KRN23
Brief summary
The primary objectives of this study are to: * Assess the long-term safety of KRN23 subcutaneous (SC) administration in adult subjects with XLH * Assess the proportion of subjects achieving serum phosphorus levels in the normal range (2.5-4.5 mg/dL) with long-term administration of KRN23 * Assess long-term pharmacodynamics (PD) of KRN23 as measured by changes in the following: serum intact parathyroid hormone (iPTH); serum and urinary phosphorus; ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate (TmP/GFR) and tubular reabsorption of phosphate (TRP); serum 1,25-dihydroxy vitamin D (1,25\[OH\]2D); serum fibroblast growth factor 23 (FGF23); bone biomarkers: serum alkaline phosphatase (ALP), bone-specific ALP (BALP), carboxy terminal crosslinked telopeptide of type I collagen (CTx), and procollagen type 1 N-terminal propeptide (P1NP) * Assess long-term immunogenicity of KRN23 as measured by presence of anti-KRN23 antibody (ADA)
Interventions
BIOLOGICALKRN23
solution for SC 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
Healthy volunteers
No
Inclusion criteria
1. Have participated in Kyowa Hakko Kirin Pharma, Inc.'s KRN23-INT-001 (NCT01340482) or KRN23-INT-002 (NCT01571596) studies (received at least 2 doses of KRN23) 2. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min or eGFR of 45 to \< 60 mL/min at Screening with confirmation that the renal insufficiency was not due to nephrocalcinosis. 3. Sexually active subjects must be willing to use an acceptable method of contraception (e.g., double barrier method) while participating in the study and for 30 days after receiving the last dose of KRN23.
Exclusion criteria
1. Subject experienced a safety-related event in the KRN23-INT-001 or KRN23-INT-002 study that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment. 2. Presence of nephrocalcinosis on renal ultrasound that, in the opinion of the investigator and sponsor, precludes resuming KRN23 treatment. 3. Pregnant or breastfeeding at Screening or planning to become pregnant (self or partner) at any time during the study. 4. Participation in an investigational drug or device trial within 30 days of enrollment (other than KRN23-INT-001 or KRN23-INT-002). 5. Use of a pharmacologic vitamin D metabolite or analog (e.g., calcitriol, doxercalciferol, and paricalcitol), phosphate, or aluminum hydroxide antacids (e.g., Maalox® and Mylanta®) within 21 days prior to Screening or during the study. 6. Use of medication to suppress parathyroid hormone (PTH) (e.g., Sensipar®, cinacalcet, calcimimetics) within 2 months prior to Screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in Total ALP | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in BALP | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in CTx | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in P1NP | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks). | An AE is defined as any untoward medical occurrence, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the investigator or sponsor, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; an important medical event. A TEAE is an AE that occurred on or after the first burosumab dose. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). AEs were classified by the Investigator as possibly related, probably related, or definitely related. |
| Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants With Clinically Significant Changes From Baseline in ECGs | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category | Through Week 184 | Clinically significant changes from baseline reported as adverse events are presented. |
| Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline | Through Week 184 | — |
| Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing | Through Week 184 | — |
| Change From Baseline Over Time in Serum Phosphorus | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in Serum iPTH | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in Serum Total FGF23 | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in Serum Free FGF23 | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in Serum 1,25(OH)2D | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in in 2-hour Urine TRP | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in FEP | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in 24-hour Urine Phosphorus | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in 24-Hour Urine Calcium | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
| Change From Baseline Over Time in 24-Hour Urine Creatinine | Baseline, Weeks 24, 48, 72, 96, 120, 144 | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| KRN23 KRN23 SC injections every 4 weeks | 20 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Other, Not Specified | 1 |
Baseline characteristics
| Characteristic | KRN23 |
|---|---|
| 24-Hour Urine Calcium | 96.118 mg/24hr STANDARD_DEVIATION 75.953 |
| 24-Hour Urine Calcium/Creatinine Ratio | 0.0881 mg/mg STANDARD_DEVIATION 0.05034 |
| 24-Hour Urine Creatinine | 1058.150 mg/24hr STANDARD_DEVIATION 444.3073 |
| 24-hour Urine Phosphorus | 0.74 g/24hr STANDARD_DEVIATION 0.322 |
| 2-hour Urine TmP/GFR | 1.583 mg/dL STANDARD_DEVIATION 0.2566 |
| 2-hour Urine Tubular Reabsorption of Phosphate (TRP) | 0.783 fraction of phosphorus reabsorbed STANDARD_DEVIATION 0.0792 |
| Age, Continuous | 49.8 years STANDARD_DEVIATION 12.87 |
| Bone-Specific Alkaline Phosphatase (BALP) | 31.26 mcg/L STANDARD_DEVIATION 18.528 |
| Carboxy Terminal Cross-Linked Telopeptide of Type I Collagen (CTx) | 732.4 pg/mL STANDARD_DEVIATION 404.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Fractional Excretion of Phosphorus (FEP) | 0.217 fraction of phosphorus excreted STANDARD_DEVIATION 0.0792 |
| Procollagen Type N-Propeptide (P1NP) | 76.5 ng/mL STANDARD_DEVIATION 41.58 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 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 | 19 Participants |
| Serum 1,25-dihydroxy vitamin D [1,25(OH)2D] | 31.7 pg/mL STANDARD_DEVIATION 12.61 |
| Serum Free FGF23 | 81.9 pg/mL STANDARD_DEVIATION 42.33 |
| Serum Intact Parathyroid Hormone (iPTH) | 110.8 pg/mL STANDARD_DEVIATION 43.7 |
| Serum Phosphorus | 1.89 mg/dL STANDARD_DEVIATION 0.301 |
| Serum Total Fibroblast Growth Factor 23 (FGF23) | 262.9 pg/mL STANDARD_DEVIATION 227.02 |
| Sex: Female, Male Female | 14 Participants |
| Sex: Female, Male Male | 6 Participants |
| Total Alkaline Phosphatase (ALP) | 131.1 U/L STANDARD_DEVIATION 50.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 20 |
| other Total, other adverse events | 20 / 20 |
| serious Total, serious adverse events | 9 / 20 |
Outcome results
Primary
Change From Baseline Over Time in 24-Hour Urine Calcium
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 24 | 22.89 mg/24hr | Standard Error 12.605 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 48 | 15.15 mg/24hr | Standard Error 8.914 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 72 | 11.10 mg/24hr | Standard Error 12.975 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 96 | -16.65 mg/24hr | Standard Error 10.637 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 120 | 3.48 mg/24hr | Standard Error 18.375 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium | Change at Week 144 | 28.55 mg/24hr | Standard Error 20.239 |
Comparison: Change at Week 2495% CI: [-1.81, 47.6]
Comparison: Change at Week 4895% CI: [-2.32, 32.62]
Comparison: Change at Week 7295% CI: [-14.33, 36.53]
Comparison: Change at Week 9695% CI: [-37.5, 4.2]
Comparison: Change at Week 12095% CI: [-32.53, 39.49]
Comparison: Change at Week 14495% CI: [-11.12, 68.22]
Primary
Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 24 | 0.01 mg/mg | Standard Error 0.01 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 48 | 0.01 mg/mg | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 72 | 0.00 mg/mg | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 96 | -0.01 mg/mg | Standard Error 0.013 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 120 | 0.00 mg/mg | Standard Error 0.013 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio | Change at Week 144 | 0.03 mg/mg | Standard Error 0.023 |
Comparison: Change at Week 2495% CI: [-0.01, 0.03]
Comparison: Change at Week 4895% CI: [-0.01, 0.04]
Comparison: Change at Week 7295% CI: [-0.02, 0.02]
Comparison: Change at Week 9695% CI: [-0.04, 0.02]
Comparison: Change at Week 12095% CI: [-0.02, 0.03]
Comparison: Change at Week 14495% CI: [-0.01, 0.08]
Primary
Change From Baseline Over Time in 24-Hour Urine Creatinine
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 24 | -14.77 mg/24hr | Standard Error 37.17 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 48 | -70.79 mg/24hr | Standard Error 46.186 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 72 | -16.11 mg/24hr | Standard Error 48.389 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 96 | -41.74 mg/24hr | Standard Error 55.546 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 120 | -76.11 mg/24hr | Standard Error 82.239 |
| KRN23 | Change From Baseline Over Time in 24-Hour Urine Creatinine | Change at Week 144 | -96.06 mg/24hr | Standard Error 56.389 |
Comparison: Change at Week 2495% CI: [-87.62, 58.08]
Comparison: Change at Week 4895% CI: [-161.31, 19.74]
Comparison: Change at Week 7295% CI: [-110.96, 78.73]
Comparison: Change at Week 9695% CI: [-150.61, 67.13]
Comparison: Change at Week 12095% CI: [-237.29, 85.08]
Comparison: Change at Week 14495% CI: [-206.59, 14.46]
Primary
Change From Baseline Over Time in 24-hour Urine Phosphorus
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 24 | -0.01 g/24hr | Standard Error 0.045 |
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 48 | 0.02 g/24hr | Standard Error 0.044 |
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 72 | 0.08 g/24hr | Standard Error 0.044 |
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 96 | -0.01 g/24hr | Standard Error 0.04 |
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 120 | -0.01 g/24hr | Standard Error 0.058 |
| KRN23 | Change From Baseline Over Time in 24-hour Urine Phosphorus | Change at Week 144 | -0.05 g/24hr | Standard Error 0.054 |
Comparison: Change at Week 2495% CI: [-0.1, 0.08]
Comparison: Change at Week 4895% CI: [-0.07, 0.1]
Comparison: Change at Week 7295% CI: [-0.01, 0.16]
Comparison: Change at Week 9695% CI: [-0.09, 0.06]
Comparison: Change at Week 12095% CI: [-0.12, 0.1]
Comparison: Change at Week 14495% CI: [-0.16, 0.06]
Primary
Change From Baseline Over Time in BALP
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 24 | 4.68 mcg/L | Standard Error 3.389 |
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 48 | -2.68 mcg/L | Standard Error 2.247 |
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 72 | -7.45 mcg/L | Standard Error 1.067 |
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 96 | -8.08 mcg/L | Standard Error 0.91 |
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 120 | -10.01 mcg/L | Standard Error 1.561 |
| KRN23 | Change From Baseline Over Time in BALP | Change at Week 144 | -10.89 mcg/L | Standard Error 1.979 |
Comparison: Change at Week 24p-value: 0.167395% CI: [-1.96, 11.32]GEE
Comparison: Change at Week 48p-value: 0.23395% CI: [-7.09, 1.72]GEE
Comparison: Change at Week 72p-value: <0.000195% CI: [-9.54, -5.36]GEE
Comparison: Change at Week 96p-value: <0.000195% CI: [-9.86, -6.29]GEE
Comparison: Change at Week 120p-value: <0.000195% CI: [-13.07, -6.95]GEE
Comparison: Change at Week 144p-value: <0.000195% CI: [-14.77, -7.02]GEE
Primary
Change From Baseline Over Time in CTx
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 24 | 343.38 pg/mL | Standard Error 135.575 |
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 48 | 41.45 pg/mL | Standard Error 61.062 |
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 72 | -61.96 pg/mL | Standard Error 63.458 |
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 96 | -68.62 pg/mL | Standard Error 63.152 |
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 120 | -53.41 pg/mL | Standard Error 50.545 |
| KRN23 | Change From Baseline Over Time in CTx | Change at Week 144 | -97.46 pg/mL | Standard Error 55.67 |
Comparison: Change at Week 144p-value: 0.0895% CI: [-206.57, 11.65]GEE
Comparison: Change at Week 24p-value: 0.011395% CI: [77.66, 609.11]GEE
Comparison: Change at Week 48p-value: 0.497295% CI: [-78.23, 161.13]GEE
Comparison: Change at Week 72p-value: 0.328895% CI: [-186.34, 62.41]GEE
Comparison: Change at Week 96p-value: 0.277295% CI: [-192.39, 55.16]GEE
Comparison: Change at Week 120p-value: 0.290795% CI: [-152.47, 45.66]GEE
Primary
Change From Baseline Over Time in FEP
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 24 | -0.04 fraction of phosphorus excreted | Standard Error 0.015 |
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 48 | -0.01 fraction of phosphorus excreted | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 72 | -0.01 fraction of phosphorus excreted | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 96 | -0.05 fraction of phosphorus excreted | Standard Error 0.012 |
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 120 | -0.01 fraction of phosphorus excreted | Standard Error 0.012 |
| KRN23 | Change From Baseline Over Time in FEP | Change at Week 144 | -0.02 fraction of phosphorus excreted | Standard Error 0.017 |
Comparison: Change at Week 2495% CI: [-0.07, -0.01]
Comparison: Change at Week 4895% CI: [-0.03, 0.01]
Comparison: Change at Week 7295% CI: [-0.04, 0.01]
Comparison: Change at Week 9695% CI: [-0.07, -0.02]
Comparison: Change at Week 12095% CI: [-0.03, 0.02]
Comparison: Change at Week 14495% CI: [-0.05, 0.01]
Primary
Change From Baseline Over Time in in 2-hour Urine TRP
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 24 | 0.04 fraction of phosphorus reabsorbed | Standard Error 0.015 |
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 48 | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 72 | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.011 |
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 96 | 0.05 fraction of phosphorus reabsorbed | Standard Error 0.012 |
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 120 | 0.01 fraction of phosphorus reabsorbed | Standard Error 0.012 |
| KRN23 | Change From Baseline Over Time in in 2-hour Urine TRP | Change at Week 144 | 0.02 fraction of phosphorus reabsorbed | Standard Error 0.017 |
Comparison: Change at Week 2495% CI: [0.01, 0.07]
Comparison: Change at Week 4895% CI: [-0.01, 0.03]
Comparison: Change at Week 7295% CI: [-0.01, 0.04]
Comparison: Change at Week 9695% CI: [0.02, 0.07]
Comparison: Change at Week 12095% CI: [-0.02, 0.03]
Comparison: Change at Week 14495% CI: [-0.01, 0.05]
Primary
Change From Baseline Over Time in P1NP
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 72 | 28.30 ng/mL | Standard Error 7.684 |
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 96 | 27.02 ng/mL | Standard Error 6.739 |
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 120 | 13.02 ng/mL | Standard Error 8.359 |
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 24 | 72.45 ng/mL | Standard Error 16.962 |
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 48 | 44.40 ng/mL | Standard Error 7.175 |
| KRN23 | Change From Baseline Over Time in P1NP | Change at Week 144 | 43.12 ng/mL | Standard Error 33.717 |
Comparison: Change at Week 96p-value: <0.000195% CI: [13.81, 40.22]GEE
Comparison: Change at Week 24p-value: <0.000195% CI: [39.21, 105.7]GEE
Comparison: Change at Week 48p-value: <0.000195% CI: [30.34, 58.47]GEE
Comparison: Change at Week 72p-value: 0.000295% CI: [13.24, 43.37]GEE
Comparison: Change at Week 120p-value: 0.119595% CI: [-3.37, 29.4]GEE
Comparison: Change at Week 144p-value: 0.200995% CI: [-22.96, 109.2]GEE
Primary
Change From Baseline Over Time in Serum 1,25(OH)2D
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 24 | 7.87 pg/mL | Standard Error 2.403 |
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 48 | 2.70 pg/mL | Standard Error 2.653 |
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 72 | 2.62 pg/mL | Standard Error 2.505 |
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 96 | 0.31 pg/mL | Standard Error 2.052 |
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 120 | -0.48 pg/mL | Standard Error 2.365 |
| KRN23 | Change From Baseline Over Time in Serum 1,25(OH)2D | Change at Week 144 | -3.43 pg/mL | Standard Error 2.844 |
Comparison: Change at Week 24p-value: 0.001195% CI: [3.16, 12.58]GEE
Comparison: Change at Week 48p-value: 0.309295% CI: [-2.5, 7.9]GEE
Comparison: Change at Week 72p-value: 0.295895% CI: [-2.29, 7.53]GEE
Comparison: Change at Week 96p-value: 0.879695% CI: [-3.71, 4.33]GEE
Comparison: Change at Week 120p-value: 0.839695% CI: [-5.11, 4.16]GEE
Comparison: Change at Week 144p-value: 0.228495% CI: [-9, 2.15]GEE
Primary
Change From Baseline Over Time in Serum Free FGF23
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 24 | 1277.84 pg/mL | Standard Error 38.521 |
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 48 | 1244.99 pg/mL | Standard Error 40.25 |
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 72 | 1298.49 pg/mL | Standard Error 33.129 |
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 96 | 1311.05 pg/mL | Standard Error 37.119 |
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 120 | 1368.68 pg/mL | Standard Error 21.063 |
| KRN23 | Change From Baseline Over Time in Serum Free FGF23 | Change at Week 144 | 1298.41 pg/mL | Standard Error 45.972 |
Comparison: Change at Week 24p-value: <0.000195% CI: [1202.34, 1353.34]GEE
Comparison: Change at Week 48p-value: <0.000195% CI: [1166.1, 1323.88]GEE
Comparison: Change at Week 72p-value: <0.000195% CI: [1233.56, 1363.43]GEE
Comparison: Change at Week 96p-value: <0.000195% CI: [1238.3, 1383.8]GEE
Comparison: Change at Week 120p-value: <0.000195% CI: [1327.4, 1409.96]GEE
Comparison: Change at Week 144p-value: <0.000195% CI: [1208.31, 1388.51]GEE
Primary
Change From Baseline Over Time in Serum iPTH
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 24 | -9.75 pg/mL | Standard Error 6.551 |
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 48 | -11.17 pg/mL | Standard Error 7.444 |
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 72 | -18.12 pg/mL | Standard Error 4.567 |
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 96 | -25.28 pg/mL | Standard Error 5.577 |
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 120 | -22.39 pg/mL | Standard Error 4.655 |
| KRN23 | Change From Baseline Over Time in Serum iPTH | Change at Week 144 | -28.33 pg/mL | Standard Error 6.007 |
Comparison: Change at Week 24p-value: 0.136695% CI: [-22.59, 3.09]GEE estimate
Comparison: Change at Week 48p-value: 0.133495% CI: [-25.76, 3.42]GEE estimate
Comparison: Change at Week 72p-value: <0.000195% CI: [-27.07, -9.17]GEE estimate
Comparison: Change at Week 96p-value: <0.000195% CI: [-36.21, -14.35]GEE estimate
Comparison: Change at Week 120p-value: <0.000195% CI: [-31.51, -13.26]GEE estimate
Comparison: Change at Week 144p-value: <0.000195% CI: [-40.11, -16.56]GEE estimate
Primary
Change From Baseline Over Time in Serum Phosphorus
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 24 | 0.68 mg/dL | Standard Error 0.103 |
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 48 | 0.68 mg/dL | Standard Error 0.055 |
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 72 | 0.59 mg/dL | Standard Error 0.077 |
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 96 | 0.47 mg/dL | Standard Error 0.081 |
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 120 | 0.57 mg/dL | Standard Error 0.082 |
| KRN23 | Change From Baseline Over Time in Serum Phosphorus | Change at Week 144 | 0.59 mg/dL | Standard Error 0.084 |
Comparison: Change at Week 24p-value: <0.000195% CI: [0.48, 0.88]generalized estimation equation (GEE)
Comparison: Change at Week 48p-value: <0.000195% CI: [0.57, 0.79]GEE
Comparison: Change at Week 72p-value: <0.000195% CI: [0.44, 0.75]GEE
Comparison: Change at Week 96p-value: <0.000195% CI: [0.31, 0.63]GEE
Comparison: Change at Week 120p-value: <0.000195% CI: [0.41, 0.73]GEE
Comparison: Change at Week 144p-value: <0.000195% CI: [0.43, 0.76]GEE
Primary
Change From Baseline Over Time in Serum Total FGF23
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 24 | 215493.38 pg/mL | Standard Error 10634.172 |
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 48 | 202525.38 pg/mL | Standard Error 17429.124 |
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 72 | 221481.03 pg/mL | Standard Error 21353.941 |
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 96 | 221674.07 pg/mL | Standard Error 20592.592 |
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 120 | 208270.02 pg/mL | Standard Error 20945.303 |
| KRN23 | Change From Baseline Over Time in Serum Total FGF23 | Change at Week 144 | 235953.55 pg/mL | Standard Error 35634.821 |
Comparison: Change at Week 24p-value: <0.000195% CI: [194650.78, 236335.97]GEE
Comparison: Change at Week 48p-value: <0.000195% CI: [168364.92, 236685.83]GEE
Comparison: Change at Week 72p-value: <0.000195% CI: [179628.07, 263333.98]GEE
Comparison: Change at Week 96p-value: <0.000195% CI: [181313.34, 262034.81]GEE
Comparison: Change at Week 120p-value: <0.000195% CI: [167217.98, 249322.06]GEE
Comparison: Change at Week 144p-value: <0.000195% CI: [166110.59, 305796.52]GEE
Primary
Change From Baseline Over Time in Total ALP
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 24 | 14.92 U/L | Standard Error 6.935 |
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 48 | -1.73 U/L | Standard Error 5.752 |
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 72 | -22.28 U/L | Standard Error 4.044 |
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 96 | -20.93 U/L | Standard Error 3.567 |
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 120 | -18.77 U/L | Standard Error 7.228 |
| KRN23 | Change From Baseline Over Time in Total ALP | Change at Week 144 | -25.72 U/L | Standard Error 5.701 |
Comparison: Change at Week 24p-value: 0.031495% CI: [1.33, 28.52]GEE
Comparison: Change at Week 48p-value: 0.76495% CI: [-13, 9.55]GEE
Comparison: Change at Week 72p-value: <0.000195% CI: [-30.2, -14.35]GEE
Comparison: Change at Week 96p-value: <0.000195% CI: [-27.92, -13.94]GEE
Comparison: Change at Week 120p-value: 0.009495% CI: [-32.93, -4.6]GEE
Comparison: Change at Week 144p-value: <0.000195% CI: [-36.89, -14.54]GEE
Primary
Change From Baseline Ovr Time in 2-hour Urine TmP/GFR
Time frame: Baseline, Weeks 24, 48, 72, 96, 120, 144
Population: PD Analysis Set (all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data) with an assessment at given time point.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 24 | 0.57 mg/dL | Standard Error 0.128 |
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 48 | 0.47 mg/dL | Standard Error 0.047 |
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 72 | 0.42 mg/dL | Standard Error 0.072 |
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 96 | 0.44 mg/dL | Standard Error 0.084 |
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 120 | 0.36 mg/dL | Standard Error 0.066 |
| KRN23 | Change From Baseline Ovr Time in 2-hour Urine TmP/GFR | Change at Week 144 | 0.47 mg/dL | Standard Error 0.078 |
Comparison: Change at Week 2495% CI: [0.32, 0.83]
Comparison: Change at Week 4895% CI: [0.37, 0.56]
Comparison: Change at Week 7295% CI: [0.28, 0.56]
Comparison: Change at Week 9695% CI: [0.27, 0.6]
Comparison: Change at Week 12095% CI: [0.23, 0.48]
Comparison: Change at Week 14495% CI: [0.32, 0.62]
Primary
Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline
Time frame: Through Week 184
Population: Participants tested for neutralizing antibodies (n=4) are those who were positive for anti-KRN23 antibodies at any time during the study.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline | Baseline: Anti-KRN23 Antibodies | 2 Participants |
| KRN23 | Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline | Post Baseline:Anti-KRN23 Antibodies | 4 Participants |
| KRN23 | Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline | Baseline: Neutralizing Antibodies | 0 Participants |
| KRN23 | Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline | Postbaseline: Neutralizing Antibodies | 0 Participants |
Primary
Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death
An AE is defined as any untoward medical occurrence, whether or not considered drug related. An SAE or serious suspected adverse reaction is an AE or suspected adverse reaction that at any dose, in the view of either the investigator or sponsor, results in any of the following outcomes: death; a life-threatening AE; inpatient hospitalization or prolongation of existing hospitalization; persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions; a congenital anomaly/birth defect; an important medical event. A TEAE is an AE that occurred on or after the first burosumab dose. AEs were graded as 1 (mild), 2 (moderate), 3 (severe), 4 (life-threatening), 5 (death). AEs were classified by the Investigator as possibly related, probably related, or definitely related.
Time frame: Screening through the end of study plus 4-8 weeks. The mean duration of burosumab exposure was 165.6 weeks (range: 68-184 weeks).
Population: Safety Analysis Set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | All AEs | 20 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | TEAEs | 20 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | Related AEs | 12 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | SAEs | 9 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | Related SAEs | 1 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | Grade 3 and 4 AEs | 10 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | AEs Leading to Discontinuation | 0 Participants |
| KRN23 | Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death | AEs Leading to Death | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in ECGs
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in ECGs | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests | 0 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated eosinophils | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hypercholesterolemia | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hyperkalemia | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hyperglycemia | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated alanine aminotransferase | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated aspartate aminotransferase | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated gamma-glutamyl transferase | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Proteinuria | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated amylase | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated alkaline phosphatase | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated lipase | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hypercalciuria | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Worsening hypercholesterolemia | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Decreased hemoglobin | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hypocalcemia (intermittent) | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hypovitaminosis D | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Elevated cholesterol | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Hyperparathyroidism | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category | Urine electrophoresis abnormal | 1 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Bone pain | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Conjunctival haemorrhage | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Hypoacusis | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Dermal cyst | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Osteoarthritis | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Gravitational oedema | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Hypoaesthesia | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Neuropathy peripheral | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Arthralgia | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Peroneal nerve palsy | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Spinal pain | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Bone lesion | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Femur fracture | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Scrotal oedema | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Synovial cyst | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Testicular swelling | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Thermal burn | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category | Weight decreased | 1 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category | Kidney stone(s) | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category | Nephrocalcinosis | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category | Right renal mass | 1 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category | Nephrolithiasis | 2 Participants |
Primary
Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Clinically significant changes from baseline reported as adverse events are presented.
Time frame: Through Week 184
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Hypertension | 2 Participants |
| KRN23 | Number of Participants With Clinically Significant Changes From Baseline in Vital Signs | Decreased blood pressure | 1 Participants |
Primary
Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing
Time frame: Through Week 184
Population: Pharmacodynamic (PD) Analysis Set: all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| KRN23 | Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing | 100 percentage of participants |