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Long-Term Extension Study of KRN23 in Adult Subjects With X-Linked Hypophosphatemia (XLH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02312687
Recruitment Status : Completed
First Posted : December 9, 2014
Results First Posted : December 16, 2019
Last Update Posted : December 16, 2019
Sponsor:
Collaborator:
Kyowa Kirin Co., Ltd.
Information provided by (Responsible Party):
Ultragenyx Pharmaceutical Inc

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition X-Linked Hypophosphatemia
Intervention Biological: KRN23
Enrollment 20
Recruitment Details  
Pre-assignment Details  
Arm/Group Title KRN23
Hide Arm/Group Description KRN23 subcutaneous (SC) injections every 4 weeks
Period Title: Overall Study
Started 20
Completed 19
Not Completed 1
Reason Not Completed
Other, Not Specified             1
Arm/Group Title KRN23
Hide Arm/Group Description KRN23 SC injections every 4 weeks
Overall Number of Baseline Participants 20
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 20 participants
49.8  (12.87)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Female
14
  70.0%
Male
6
  30.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
Hispanic or Latino
1
   5.0%
Not Hispanic or Latino
19
  95.0%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 20 participants
American Indian or Alaska Native
0
   0.0%
Asian
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   5.0%
White
19
  95.0%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Serum Phosphorus  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 20 participants
1.89  (0.301)
Serum Intact Parathyroid Hormone (iPTH)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 20 participants
110.8  (43.70)
Serum Total Fibroblast Growth Factor 23 (FGF23)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 20 participants
262.9  (227.02)
Serum Free FGF23  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 20 participants
81.9  (42.33)
Serum 1,25-dihydroxy vitamin D [1,25(OH)2D]  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 20 participants
31.7  (12.61)
2-hour Urine TmP/GFR   [1] 
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 20 participants
1.583  (0.2566)
[1]
Measure Description: TmP/GFR: ratio of renal tubular maximum phosphate reabsorption rate to glomerular filtration rate
2-hour Urine Tubular Reabsorption of Phosphate (TRP)  
Mean (Standard Deviation)
Unit of measure:  Fraction of phosphorus reabsorbed
Number Analyzed 20 participants
0.783  (0.0792)
Fractional Excretion of Phosphorus (FEP)  
Mean (Standard Deviation)
Unit of measure:  Fraction of phosphorus excreted
Number Analyzed 20 participants
0.217  (0.0792)
24-hour Urine Phosphorus  
Mean (Standard Deviation)
Unit of measure:  G/24hr
Number Analyzed 20 participants
0.74  (0.322)
24-Hour Urine Calcium   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/24hr
Number Analyzed 17 participants
96.118  (75.9530)
[1]
Measure Analysis Population Description: participants with an assessment
24-Hour Urine Creatinine  
Mean (Standard Deviation)
Unit of measure:  Mg/24hr
Number Analyzed 20 participants
1058.150  (444.3073)
24-Hour Urine Calcium/Creatinine Ratio   [1] 
Mean (Standard Deviation)
Unit of measure:  Mg/mg
Number Analyzed 17 participants
0.0881  (0.05034)
[1]
Measure Analysis Population Description: participants with an assessment
Total Alkaline Phosphatase (ALP)  
Mean (Standard Deviation)
Unit of measure:  U/L
Number Analyzed 20 participants
131.1  (50.50)
Bone-Specific Alkaline Phosphatase (BALP)  
Mean (Standard Deviation)
Unit of measure:  mcg/L
Number Analyzed 20 participants
31.26  (18.528)
Carboxy Terminal Cross-Linked Telopeptide of Type I Collagen (CTx)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 20 participants
732.4  (404.01)
Procollagen Type N-Propeptide (P1NP)  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 20 participants
76.5  (41.58)
1.Primary Outcome
Title Number of Participants With Adverse Events (AEs), Treatment Emergent AEs (TEAEs), Serious AEs (SAEs), and AEs Leading to Discontinuation or Death
Hide Description 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).
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Analysis Set
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
All AEs
20
 100.0%
TEAEs
20
 100.0%
Related AEs
12
  60.0%
SAEs
9
  45.0%
Related SAEs
1
   5.0%
Grade 3 and 4 AEs
10
  50.0%
AEs Leading to Discontinuation
0
   0.0%
AEs Leading to Death
0
   0.0%
2.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Vital Signs
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Hypertension
2
  10.0%
Decreased blood pressure
1
   5.0%
3.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Laboratory Values, by Category
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Elevated eosinophils
1
   5.0%
Hypercholesterolemia
1
   5.0%
Hyperkalemia
1
   5.0%
Hyperglycemia
1
   5.0%
Elevated alanine aminotransferase
1
   5.0%
Elevated aspartate aminotransferase
1
   5.0%
Elevated gamma-glutamyl transferase
2
  10.0%
Proteinuria
2
  10.0%
Elevated amylase
2
  10.0%
Elevated alkaline phosphatase
1
   5.0%
Elevated lipase
1
   5.0%
Hypercalciuria
1
   5.0%
Worsening hypercholesterolemia
2
  10.0%
Decreased hemoglobin
2
  10.0%
Hypocalcemia (intermittent)
1
   5.0%
Hypovitaminosis D
1
   5.0%
Elevated cholesterol
1
   5.0%
Hyperparathyroidism
1
   5.0%
Urine electrophoresis abnormal
1
   5.0%
4.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Physical Exams, by Category
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Bone pain
1
   5.0%
Conjunctival haemorrhage
1
   5.0%
Hypoacusis
1
   5.0%
Dermal cyst
1
   5.0%
Osteoarthritis
1
   5.0%
Gravitational oedema
1
   5.0%
Hypoaesthesia
1
   5.0%
Neuropathy peripheral
2
  10.0%
Arthralgia
1
   5.0%
Peroneal nerve palsy
1
   5.0%
Spinal pain
1
   5.0%
Bone lesion
1
   5.0%
Femur fracture
1
   5.0%
Scrotal oedema
1
   5.0%
Synovial cyst
1
   5.0%
Testicular swelling
1
   5.0%
Thermal burn
1
   5.0%
Weight decreased
1
   5.0%
5.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Echocardiogram (ECHO) Tests
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
6.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in ECGs
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
7.Primary Outcome
Title Number of Participants With Clinically Significant Changes From Baseline in Renal Ultrasound, by Category
Hide Description Clinically significant changes from baseline reported as adverse events are presented.
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Kidney stone(s)
1
   5.0%
Nephrocalcinosis
1
   5.0%
Right renal mass
1
   5.0%
Nephrolithiasis
2
  10.0%
8.Primary Outcome
Title Number of Participants Positive for Anti-KRN23 Antibodies and Neutralizing Antibodies at Baseline and Anytime Post-Baseline
Hide Description [Not Specified]
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
Participants tested for neutralizing antibodies (n=4) are those who were positive for anti-KRN23 antibodies at any time during the study.
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline: Anti-KRN23 Antibodies Number Analyzed 20 participants
2
  10.0%
Post Baseline:Anti-KRN23 Antibodies Number Analyzed 20 participants
4
  20.0%
Baseline: Neutralizing Antibodies Number Analyzed 2 participants
0
   0.0%
Postbaseline: Neutralizing Antibodies Number Analyzed 4 participants
0
   0.0%
9.Primary Outcome
Title Percentage of Participants Reaching Serum Phosphorus Normal Range at Baseline and Any Time After Dosing
Hide Description [Not Specified]
Time Frame Through Week 184
Hide Outcome Measure Data
Hide Analysis Population Description
Pharmacodynamic (PD) Analysis Set: all participants who received at least 1 dose of burosumab and had evaluable serum/urinary data.
Arm/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
100
(83.9 to 100.0)
10.Primary Outcome
Title Change From Baseline Over Time in Serum Phosphorus
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Change at Week 24 Number Analyzed 16 participants
0.68  (0.103)
Change at Week 48 Number Analyzed 19 participants
0.68  (0.055)
Change at Week 72 Number Analyzed 20 participants
0.59  (0.077)
Change at Week 96 Number Analyzed 19 participants
0.47  (0.081)
Change at Week 120 Number Analyzed 18 participants
0.57  (0.082)
Change at Week 144 Number Analyzed 18 participants
0.59  (0.084)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The generalized estimation equation (GEE) model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method generalized estimation equation (GEE)
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares (LS) Mean
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.48 to 0.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.68
Confidence Interval (2-Sided) 95%
0.57 to 0.79
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.44 to 0.75
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.31 to 0.63
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.41 to 0.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.59
Confidence Interval (2-Sided) 95%
0.43 to 0.76
Estimation Comments [Not Specified]
11.Primary Outcome
Title Change From Baseline Over Time in Serum iPTH
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 24 Number Analyzed 18 participants
-9.75  (6.551)
Change at Week 48 Number Analyzed 20 participants
-11.17  (7.444)
Change at Week 72 Number Analyzed 20 participants
-18.12  (4.567)
Change at Week 96 Number Analyzed 19 participants
-25.28  (5.577)
Change at Week 120 Number Analyzed 19 participants
-22.39  (4.655)
Change at Week 144 Number Analyzed 19 participants
-28.33  (6.007)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1366
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -9.75
Confidence Interval (2-Sided) 95%
-22.59 to 3.09
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1334
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -11.17
Confidence Interval (2-Sided) 95%
-25.76 to 3.42
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -18.12
Confidence Interval (2-Sided) 95%
-27.07 to -9.17
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -25.28
Confidence Interval (2-Sided) 95%
-36.21 to -14.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -22.39
Confidence Interval (2-Sided) 95%
-31.51 to -13.26
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE estimate
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -28.33
Confidence Interval (2-Sided) 95%
-40.11 to -16.56
Estimation Comments [Not Specified]
12.Primary Outcome
Title Change From Baseline Over Time in Serum Total FGF23
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 24 Number Analyzed 20 participants
215493.38  (10634.172)
Change at Week 48 Number Analyzed 20 participants
202525.38  (17429.124)
Change at Week 72 Number Analyzed 20 participants
221481.03  (21353.941)
Change at Week 96 Number Analyzed 19 participants
221674.07  (20592.592)
Change at Week 120 Number Analyzed 19 participants
208270.02  (20945.303)
Change at Week 144 Number Analyzed 17 participants
235953.55  (35634.821)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 215493.38
Confidence Interval (2-Sided) 95%
194650.78 to 236335.97
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 202525.38
Confidence Interval (2-Sided) 95%
168364.92 to 236685.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 221481.03
Confidence Interval (2-Sided) 95%
179628.07 to 263333.98
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 221674.07
Confidence Interval (2-Sided) 95%
181313.34 to 262034.81
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 208270.02
Confidence Interval (2-Sided) 95%
167217.98 to 249322.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 235953.55
Confidence Interval (2-Sided) 95%
166110.59 to 305796.52
Estimation Comments [Not Specified]
13.Primary Outcome
Title Change From Baseline Over Time in Serum Free FGF23
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 24 Number Analyzed 20 participants
1277.84  (38.521)
Change at Week 48 Number Analyzed 20 participants
1244.99  (40.250)
Change at Week 72 Number Analyzed 20 participants
1298.49  (33.129)
Change at Week 96 Number Analyzed 19 participants
1311.05  (37.119)
Change at Week 120 Number Analyzed 19 participants
1368.68  (21.063)
Change at Week 144 Number Analyzed 17 participants
1298.41  (45.972)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1277.84
Confidence Interval (2-Sided) 95%
1202.34 to 1353.34
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1244.99
Confidence Interval (2-Sided) 95%
1166.10 to 1323.88
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1298.49
Confidence Interval (2-Sided) 95%
1233.56 to 1363.43
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1311.05
Confidence Interval (2-Sided) 95%
1238.30 to 1383.80
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1368.68
Confidence Interval (2-Sided) 95%
1327.40 to 1409.96
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1298.41
Confidence Interval (2-Sided) 95%
1208.31 to 1388.51
Estimation Comments [Not Specified]
14.Primary Outcome
Title Change From Baseline Over Time in Serum 1,25(OH)2D
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 24 Number Analyzed 20 participants
7.87  (2.403)
Change at Week 48 Number Analyzed 19 participants
2.70  (2.653)
Change at Week 72 Number Analyzed 20 participants
2.62  (2.505)
Change at Week 96 Number Analyzed 19 participants
0.31  (2.052)
Change at Week 120 Number Analyzed 19 participants
-0.48  (2.365)
Change at Week 144 Number Analyzed 19 participants
-3.43  (2.844)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0011
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 7.87
Confidence Interval (2-Sided) 95%
3.16 to 12.58
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3092
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 2.70
Confidence Interval (2-Sided) 95%
-2.50 to 7.90
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2958
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 2.62
Confidence Interval (2-Sided) 95%
-2.29 to 7.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8796
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.31
Confidence Interval (2-Sided) 95%
-3.71 to 4.33
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8396
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.48
Confidence Interval (2-Sided) 95%
-5.11 to 4.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2284
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -3.43
Confidence Interval (2-Sided) 95%
-9.00 to 2.15
Estimation Comments [Not Specified]
15.Primary Outcome
Title Change From Baseline Ovr Time in 2-hour Urine TmP/GFR
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Change at Week 24 Number Analyzed 16 participants
0.57  (0.128)
Change at Week 48 Number Analyzed 19 participants
0.47  (0.047)
Change at Week 72 Number Analyzed 20 participants
0.42  (0.072)
Change at Week 96 Number Analyzed 19 participants
0.44  (0.084)
Change at Week 120 Number Analyzed 18 participants
0.36  (0.066)
Change at Week 144 Number Analyzed 18 participants
0.47  (0.078)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.57
Confidence Interval (2-Sided) 95%
0.32 to 0.83
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.37 to 0.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.28 to 0.56
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.27 to 0.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.36
Confidence Interval (2-Sided) 95%
0.23 to 0.48
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.47
Confidence Interval (2-Sided) 95%
0.32 to 0.62
Estimation Comments [Not Specified]
16.Primary Outcome
Title Change From Baseline Over Time in in 2-hour Urine TRP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: fraction of phosphorus reabsorbed
Change at Week 24 Number Analyzed 18 participants
0.04  (0.015)
Change at Week 48 Number Analyzed 19 participants
0.01  (0.011)
Change at Week 72 Number Analyzed 20 participants
0.01  (0.011)
Change at Week 96 Number Analyzed 19 participants
0.05  (0.012)
Change at Week 120 Number Analyzed 18 participants
0.01  (0.012)
Change at Week 144 Number Analyzed 18 participants
0.02  (0.017)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.01 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.01 to 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.01 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.05
Confidence Interval (2-Sided) 95%
0.02 to 0.07
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.01 to 0.05
Estimation Comments [Not Specified]
17.Primary Outcome
Title Change From Baseline Over Time in FEP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: fraction of phosphorus excreted
Change at Week 24 Number Analyzed 18 participants
-0.04  (0.015)
Change at Week 48 Number Analyzed 19 participants
-0.01  (0.011)
Change at Week 72 Number Analyzed 20 participants
-0.01  (0.011)
Change at Week 96 Number Analyzed 19 participants
-0.05  (0.012)
Change at Week 120 Number Analyzed 18 participants
-0.01  (0.012)
Change at Week 144 Number Analyzed 18 participants
-0.02  (0.017)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.07 to -0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.04 to 0.01
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.07 to -0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.03 to 0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.05 to 0.01
Estimation Comments [Not Specified]
18.Primary Outcome
Title Change From Baseline Over Time in 24-hour Urine Phosphorus
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: g/24hr
Change at Week 24 Number Analyzed 18 participants
-0.01  (0.045)
Change at Week 48 Number Analyzed 20 participants
0.02  (0.044)
Change at Week 72 Number Analyzed 19 participants
0.08  (0.044)
Change at Week 96 Number Analyzed 19 participants
-0.01  (0.040)
Change at Week 120 Number Analyzed 19 participants
-0.01  (0.058)
Change at Week 144 Number Analyzed 16 participants
-0.05  (0.054)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.10 to 0.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.07 to 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.08
Confidence Interval (2-Sided) 95%
-0.01 to 0.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.09 to 0.06
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.12 to 0.10
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.05
Confidence Interval (2-Sided) 95%
-0.16 to 0.06
Estimation Comments [Not Specified]
19.Primary Outcome
Title Change From Baseline Over Time in 24-Hour Urine Calcium
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mg/24hr
Change at Week 24 Number Analyzed 13 participants
22.89  (12.605)
Change at Week 48 Number Analyzed 15 participants
15.15  (8.914)
Change at Week 72 Number Analyzed 14 participants
11.10  (12.975)
Change at Week 96 Number Analyzed 12 participants
-16.65  (10.637)
Change at Week 120 Number Analyzed 13 participants
3.48  (18.375)
Change at Week 144 Number Analyzed 14 participants
28.55  (20.239)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 22.89
Confidence Interval (2-Sided) 95%
-1.81 to 47.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 15.15
Confidence Interval (2-Sided) 95%
-2.32 to 32.62
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 11.10
Confidence Interval (2-Sided) 95%
-14.33 to 36.53
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -16.65
Confidence Interval (2-Sided) 95%
-37.50 to 4.20
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 3.48
Confidence Interval (2-Sided) 95%
-32.53 to 39.49
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 28.55
Confidence Interval (2-Sided) 95%
-11.12 to 68.22
Estimation Comments [Not Specified]
20.Primary Outcome
Title Change From Baseline Over Time in 24-Hour Urine Creatinine
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mg/24hr
Change at Week 24 Number Analyzed 18 participants
-14.77  (37.170)
Change at Week 48 Number Analyzed 20 participants
-70.79  (46.186)
Change at Week 72 Number Analyzed 19 participants
-16.11  (48.389)
Change at Week 96 Number Analyzed 19 participants
-41.74  (55.546)
Change at Week 120 Number Analyzed 19 participants
-76.11  (82.239)
Change at Week 144 Number Analyzed 17 participants
-96.06  (56.389)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -14.77
Confidence Interval (2-Sided) 95%
-87.62 to 58.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -70.79
Confidence Interval (2-Sided) 95%
-161.31 to 19.74
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -16.11
Confidence Interval (2-Sided) 95%
-110.96 to 78.73
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -41.74
Confidence Interval (2-Sided) 95%
-150.61 to 67.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -76.11
Confidence Interval (2-Sided) 95%
-237.29 to 85.08
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -96.06
Confidence Interval (2-Sided) 95%
-206.59 to 14.46
Estimation Comments [Not Specified]
21.Primary Outcome
Title Change From Baseline Over Time in 24-Hour Urine Calcium/Creatinine Ratio
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mg/mg
Change at Week 24 Number Analyzed 13 participants
0.01  (0.010)
Change at Week 48 Number Analyzed 15 participants
0.01  (0.011)
Change at Week 72 Number Analyzed 14 participants
0.00  (0.011)
Change at Week 96 Number Analyzed 12 participants
-0.01  (0.013)
Change at Week 120 Number Analyzed 13 participants
0.00  (0.013)
Change at Week 144 Number Analyzed 14 participants
0.03  (0.023)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.01 to 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.01 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.02 to 0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.04 to 0.02
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.02 to 0.03
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.01 to 0.08
Estimation Comments [Not Specified]
22.Primary Outcome
Title Change From Baseline Over Time in Total ALP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: U/L
Change at Week 24 Number Analyzed 20 participants
14.92  (6.935)
Change at Week 48 Number Analyzed 20 participants
-1.73  (5.752)
Change at Week 72 Number Analyzed 20 participants
-22.28  (4.044)
Change at Week 96 Number Analyzed 19 participants
-20.93  (3.567)
Change at Week 120 Number Analyzed 19 participants
-18.77  (7.228)
Change at Week 144 Number Analyzed 19 participants
-25.72  (5.701)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0314
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 14.92
Confidence Interval (2-Sided) 95%
1.33 to 28.52
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7640
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -1.73
Confidence Interval (2-Sided) 95%
-13.00 to 9.55
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -22.28
Confidence Interval (2-Sided) 95%
-30.20 to -14.35
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -20.93
Confidence Interval (2-Sided) 95%
-27.92 to -13.94
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0094
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -18.77
Confidence Interval (2-Sided) 95%
-32.93 to -4.60
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -25.72
Confidence Interval (2-Sided) 95%
-36.89 to -14.54
Estimation Comments [Not Specified]
23.Primary Outcome
Title Change From Baseline Over Time in BALP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: mcg/L
Change at Week 24 Number Analyzed 18 participants
4.68  (3.389)
Change at Week 48 Number Analyzed 20 participants
-2.68  (2.247)
Change at Week 72 Number Analyzed 19 participants
-7.45  (1.067)
Change at Week 96 Number Analyzed 19 participants
-8.08  (0.910)
Change at Week 120 Number Analyzed 19 participants
-10.01  (1.561)
Change at Week 144 Number Analyzed 16 participants
-10.89  (1.979)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1673
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 4.68
Confidence Interval (2-Sided) 95%
-1.96 to 11.32
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2330
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -2.68
Confidence Interval (2-Sided) 95%
-7.09 to 1.72
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -7.45
Confidence Interval (2-Sided) 95%
-9.54 to -5.36
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -8.08
Confidence Interval (2-Sided) 95%
-9.86 to -6.29
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -10.01
Confidence Interval (2-Sided) 95%
-13.07 to -6.95
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -10.89
Confidence Interval (2-Sided) 95%
-14.77 to -7.02
Estimation Comments [Not Specified]
24.Primary Outcome
Title Change From Baseline Over Time in CTx
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Change at Week 24 Number Analyzed 18 participants
343.38  (135.575)
Change at Week 48 Number Analyzed 20 participants
41.45  (61.062)
Change at Week 72 Number Analyzed 19 participants
-61.96  (63.458)
Change at Week 96 Number Analyzed 19 participants
-68.62  (63.152)
Change at Week 120 Number Analyzed 19 participants
-53.41  (50.545)
Change at Week 144 Number Analyzed 19 participants
-97.46  (55.670)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0113
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 343.38
Confidence Interval (2-Sided) 95%
77.66 to 609.11
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.4972
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 41.45
Confidence Interval (2-Sided) 95%
-78.23 to 161.13
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3288
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -61.96
Confidence Interval (2-Sided) 95%
-186.34 to 62.41
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2772
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -68.62
Confidence Interval (2-Sided) 95%
-192.39 to 55.16
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2907
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -53.41
Confidence Interval (2-Sided) 95%
-152.47 to 45.66
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0800
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -97.46
Confidence Interval (2-Sided) 95%
-206.57 to 11.65
Estimation Comments [Not Specified]
25.Primary Outcome
Title Change From Baseline Over Time in P1NP
Hide Description [Not Specified]
Time Frame Baseline, Weeks 24, 48, 72, 96, 120, 144
Hide Outcome Measure Data
Hide Analysis Population Description
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/Group Title KRN23
Hide Arm/Group Description:
KRN23 SC injections every 4 weeks
Overall Number of Participants Analyzed 20
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Change at Week 24 Number Analyzed 20 participants
72.45  (16.962)
Change at Week 48 Number Analyzed 20 participants
44.40  (7.175)
Change at Week 72 Number Analyzed 20 participants
28.30  (7.684)
Change at Week 96 Number Analyzed 19 participants
27.02  (6.739)
Change at Week 120 Number Analyzed 19 participants
13.02  (8.359)
Change at Week 144 Number Analyzed 19 participants
43.12  (33.717)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 72.45
Confidence Interval (2-Sided) 95%
39.21 to 105.70
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 48
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 44.40
Confidence Interval (2-Sided) 95%
30.34 to 58.47
Estimation Comments [Not Specified]
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 72
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 28.30
Confidence Interval (2-Sided) 95%
13.24 to 43.37
Estimation Comments [Not Specified]
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 96
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 27.02
Confidence Interval (2-Sided) 95%
13.81 to 40.22
Estimation Comments [Not Specified]
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 120
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1195
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 13.02
Confidence Interval (2-Sided) 95%
-3.37 to 29.40
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection KRN23
Comments Change at Week 144
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2009
Comments The GEE model includes the change from baseline as the dependent variable, time as the categorical variable and adjusted for baseline measurement, with compound symmetry covariance structure.
Method GEE
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 43.12
Confidence Interval (2-Sided) 95%
-22.96 to 109.20
Estimation Comments [Not Specified]
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).
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title KRN23
Hide Arm/Group Description KRN23 SC injections every 4 weeks
All-Cause Mortality
KRN23
Affected / at Risk (%)
Total   0/20 (0.00%) 
Hide Serious Adverse Events
KRN23
Affected / at Risk (%)
Total   9/20 (45.00%) 
Congenital, familial and genetic disorders   
Hereditary Non-Polyposis Colorectal Cancer Syndrome  1  1/20 (5.00%) 
Gastrointestinal disorders   
Small Intestinal Obstruction  1  1/20 (5.00%) 
Hepatobiliary disorders   
Cholecystitis Acute  1  1/20 (5.00%) 
Infections and infestations   
Medical Device Site Joint Infection  1  1/20 (5.00%) 
Musculoskeletal and connective tissue disorders   
Musculoskeletal Chest Pain  1  1/20 (5.00%) 
Osteoarthritis  1  1/20 (5.00%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Adenocarcinoma Of Colon  1  1/20 (5.00%) 
Chordoma  1  1/20 (5.00%) 
Lung Adenocarcinoma  1  1/20 (5.00%) 
Nervous system disorders   
Hemianaesthesia  1  1/20 (5.00%) 
Hemiparesis  1  1/20 (5.00%) 
Skin and subcutaneous tissue disorders   
Angioedema  1  1/20 (5.00%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
KRN23
Affected / at Risk (%)
Total   20/20 (100.00%) 
Cardiac disorders   
Atrial Fibrillation  1  1/20 (5.00%) 
Palpitations  1  1/20 (5.00%) 
Ear and labyrinth disorders   
Hypoacusis  1  2/20 (10.00%) 
Tinnitus  1  1/20 (5.00%) 
Vertigo  1  3/20 (15.00%) 
Vertigo Positional  1  1/20 (5.00%) 
Endocrine disorders   
Hyperparathyroidism  1  1/20 (5.00%) 
Eye disorders   
Cataract  1  2/20 (10.00%) 
Conjunctival Haemorrhage  1  1/20 (5.00%) 
Diplopia  1  1/20 (5.00%) 
Dry Eye  1  1/20 (5.00%) 
Vision Blurred  1  1/20 (5.00%) 
Visual Impairment  1  1/20 (5.00%) 
Vitreous Floaters  1  1/20 (5.00%) 
Gastrointestinal disorders   
Abdominal Distension  1  1/20 (5.00%) 
Abdominal Pain  1  1/20 (5.00%) 
Abdominal Pain Lower  1  2/20 (10.00%) 
Constipation  1  2/20 (10.00%) 
Diarrhoea  1  3/20 (15.00%) 
Dyspepsia  1  2/20 (10.00%) 
Faecal Incontinence  1  1/20 (5.00%) 
Gastritis  1  1/20 (5.00%) 
Gastrooesophageal Reflux Disease  1  2/20 (10.00%) 
Ileus  1  1/20 (5.00%) 
Intestinal Dilatation  1  1/20 (5.00%) 
Irritable Bowel Syndrome  1  1/20 (5.00%) 
Large Intestinal Stenosis  1  1/20 (5.00%) 
Nausea  1  6/20 (30.00%) 
Pancreatic Calcification  1  1/20 (5.00%) 
Pancreatic Duct Dilatation  1  1/20 (5.00%) 
Vomiting  1  5/20 (25.00%) 
General disorders   
Asthenia  1  1/20 (5.00%) 
Cyst  1  1/20 (5.00%) 
Fatigue  1  4/20 (20.00%) 
Gravitational Oedema  1  1/20 (5.00%) 
Injection Site Erythema  1  3/20 (15.00%) 
Injection Site Pain  1  1/20 (5.00%) 
Injection Site Reaction  1  4/20 (20.00%) 
Medical Device Site Pain  1  1/20 (5.00%) 
Pain  1  2/20 (10.00%) 
Pyrexia  1  1/20 (5.00%) 
Tenderness  1  1/20 (5.00%) 
Hepatobiliary disorders   
Ampulla Of Vater Stenosis  1  1/20 (5.00%) 
Biliary Dilatation  1  1/20 (5.00%) 
Hepatic Steatosis  1  2/20 (10.00%) 
Immune system disorders   
Seasonal Allergy  1  2/20 (10.00%) 
Infections and infestations   
Arthritis Infective  1  1/20 (5.00%) 
Breast Abscess  1  1/20 (5.00%) 
Bronchitis  1  4/20 (20.00%) 
Cystitis  1  1/20 (5.00%) 
Ear Infection  1  3/20 (15.00%) 
Gingivitis  1  1/20 (5.00%) 
Herpes Zoster  1  1/20 (5.00%) 
Hordeolum  1  1/20 (5.00%) 
Incision Site Infection  1  1/20 (5.00%) 
Infected Bite  1  1/20 (5.00%) 
Influenza  1  1/20 (5.00%) 
Localised Infection  1  1/20 (5.00%) 
Lyme Disease  1  1/20 (5.00%) 
Nasopharyngitis  1  7/20 (35.00%) 
Otitis Externa  1  1/20 (5.00%) 
Pharyngitis Streptococcal  1  1/20 (5.00%) 
Pneumonia  1  1/20 (5.00%) 
Respiratory Tract Infection  1  1/20 (5.00%) 
Sepsis  1  1/20 (5.00%) 
Sinusitis  1  3/20 (15.00%) 
Sinusitis Bacterial  1  1/20 (5.00%) 
Tooth Abscess  1  2/20 (10.00%) 
Tooth Infection  1  2/20 (10.00%) 
Upper Respiratory Tract Infection  1  5/20 (25.00%) 
Urinary Tract Infection  1  2/20 (10.00%) 
Urinary Tract Infection Enterococcal  1  1/20 (5.00%) 
Injury, poisoning and procedural complications   
Arthropod Bite  1  1/20 (5.00%) 
Contusion  1  2/20 (10.00%) 
Fall  1  6/20 (30.00%) 
Femur Fracture  1  1/20 (5.00%) 
Hand Fracture  1  2/20 (10.00%) 
Ligament Sprain  1  1/20 (5.00%) 
Meniscus Injury  1  2/20 (10.00%) 
Procedural Hypertension  1  1/20 (5.00%) 
Procedural Nausea  1  1/20 (5.00%) 
Procedural Pain  1  2/20 (10.00%) 
Seroma  1  1/20 (5.00%) 
Sunburn  1  1/20 (5.00%) 
Thermal Burn  1  1/20 (5.00%) 
Tooth Fracture  1  3/20 (15.00%) 
Tooth Injury  1  1/20 (5.00%) 
Investigations   
Alanine Aminotransferase Increased  1  1/20 (5.00%) 
Amylase Increased  1  2/20 (10.00%) 
Aspartate Aminotransferase Increased  1  1/20 (5.00%) 
Blood Alkaline Phosphatase Increased  1  1/20 (5.00%) 
Blood Cholesterol Increased  1  1/20 (5.00%) 
Blood Iron Decreased  1  1/20 (5.00%) 
Blood Pressure Decreased  1  1/20 (5.00%) 
Eosinophil Count Increased  1  1/20 (5.00%) 
Gamma-Glutamyltransferase Increased  1  2/20 (10.00%) 
Haemoglobin Decreased  1  1/20 (5.00%) 
Lipase Increased  1  1/20 (5.00%) 
Oxygen Saturation Decreased  1  1/20 (5.00%) 
Smear Cervix Abnormal  1  1/20 (5.00%) 
Urine Electrophoresis Abnormal  1  1/20 (5.00%)