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Open Label Study of KRN23 on Osteomalacia in Adults 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: NCT02537431
Recruitment Status : Completed
First Posted : September 1, 2015
Results First Posted : September 25, 2018
Last Update Posted : December 23, 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: burosumab
Enrollment 14
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description 1.0 mg/kg burosumab monthly (Q4W), calculated based on baseline weight and up to a maximum dose of 90 mg.
Period Title: Open-Label Period (Week 0 to Week 48)
Started 14 [1]
Completed 13 [2]
Not Completed 1
Reason Not Completed
Withdrawal by Subject             1
[1]
Screened and received at least 1 dose of study drug.
[2]
Completed Open-Label Period (Week 0 - Week 48)
Period Title: Treatment Extension Period I
Started 13
Completed 13
Not Completed 0
Period Title: Treatment Extension Period II
Started 8 [1]
Completed 8
Not Completed 0
[1]
5 participants completing Treatment Extension Period I did not enter Treatment Extension Period II
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description 1.0 mg/kg Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Baseline Participants 14
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants
40.13  (8.725)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Female
8
  57.1%
Male
6
  42.9%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
Hispanic or Latino
1
   7.1%
Not Hispanic or Latino
13
  92.9%
Unknown or Not Reported
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants
American Indian or Alaska Native
0
   0.0%
Asian
4
  28.6%
Native Hawaiian or Other Pacific Islander
0
   0.0%
Black or African American
1
   7.1%
White
9
  64.3%
More than one race
0
   0.0%
Unknown or Not Reported
0
   0.0%
Osteoid Volume/Bone Volume (OV/BV)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of osteoid volume
Number Analyzed 10 participants
26.12  (12.357)
[1]
Measure Description: Percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Serum Phosphorus  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 14 participants
2.24  (0.396)
Osteoid Thickness (O.Th)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  µm
Number Analyzed 11 participants
17.21  (4.105)
[1]
Measure Description: Mean thickness, given in micrometers, for osteoid seams.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
Osteoid Surface/Bone Surface (OS/BS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of osteoid surface
Number Analyzed 11 participants
91.73  (3.438)
[1]
Measure Description: Percent of bone surface covered in osteoid.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
Mineralization Lag Time (MLt)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Days
Number Analyzed 11 participants
1539.81  (1587.086)
[1]
Measure Description: Average time interval between osteoid formation and its subsequent mineralization; calculated by dividing the osteoid thickness by the adjusted apposition rate (O.Th/Aj.AR). Aj.AR; amount of new bone created (bone formation rate over the entire osteoid surface). The imputed result was used for some of the baseline data for MLt.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
Mineral Apposition Rate (MAR)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  µm/day
Number Analyzed 11 participants
0.58  (0.448)
[1]
Measure Description: Linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
Mineralizing Surface/Bone Surface (MS/BS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percentage of mineralizing surface
Number Analyzed 11 participants
5.99  (4.763)
[1]
Measure Description: Percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface ([dLS + sLS/2]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
Bone Formation Rate/Bone Surface (BFR/BS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  µm^3/µm^2/year
Number Analyzed 6 participants
26.68  (19.480)
[1]
Measure Description: Amount of new bone formed in unit time per unit of bone surface; calculated by multiplying MS/BS by the MAR (see previous measure descriptions for MS/BS and MAR definitions).
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Bone Formation Rate/Osteoblast Surface (BFR/OS)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  µm^3/µm^2/year
Number Analyzed 4 participants
2309.00  (2941.970)
[1]
Measure Description: Bone formation rate to osteoid surface ratio, related to the adjusted apposition rate (Aj.AR; amount of new bone created [bone formation rate over the entire osteoid surface]).
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Bone Formation Rate/Bone Volume (BFR/BV)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Percent/year
Number Analyzed 6 participants
38.33  (37.173)
[1]
Measure Description: BFR/BV is equivalent to bone turnover rate.
[2]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
1,25(OH) 2D   [1] 
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 12 participants
37.25  (11.686)
[1]
Measure Analysis Population Description: Full Analysis Set: enrolled and dosed participants with a baseline measurement.
24-Hour Urinary Phosphorus   [1] 
Mean (Standard Deviation)
Unit of measure:  G/24hr
Number Analyzed 12 participants
0.82  (0.237)
[1]
Measure Analysis Population Description: Full Analysis Set: enrolled and dosed participants with a baseline measurement.
Ratio of Renal Tubular Maximum Reabsorption Rate of Phosphate to Glomerular Filtration Rate(TmP/GFR)  
Mean (Standard Deviation)
Unit of measure:  mg/dL
Number Analyzed 14 participants
1.87  (0.307)
Tubular Reabsorption of Phosphate (TRP)  
Mean (Standard Deviation)
Unit of measure:  Fraction of phosphorus reabsorbed
Number Analyzed 14 participants
0.84  (0.048)
Procollagen Type 1 N-Propeptide (P1NP)  
Mean (Standard Deviation)
Unit of measure:  ng/mL
Number Analyzed 14 participants
77.00  (33.273)
Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx-I)  
Mean (Standard Deviation)
Unit of measure:  pg/mL
Number Analyzed 14 participants
646.93  (401.641)
Bone-Specific Alkaline Phosphatase (BALP)  
Mean (Standard Deviation)
Unit of measure:  μg/L
Number Analyzed 14 participants
20.43  (9.288)
Mineralizing Surface/OsteoidSurface (MS/OS)   [1] 
Mean (Standard Deviation)
Unit of measure:  Percentage of mineralizing surface
Number Analyzed 11 participants
6.47  (5.120)
[1]
Measure Analysis Population Description: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
1.Primary Outcome
Title Percent Change From Baseline in OV/BV at Week 48
Hide Description OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percentage change of unmineralized bone
-54.18  (20.211)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments The null hypothesis of no mean percent change from baseline is tested using t-test.
Method t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean
Estimated Value -54.18
Confidence Interval (2-Sided) 95%
-68.64 to -39.72
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% confidence interval (CI) was calculated using Wilson score method.
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
92.9
(68.5 to 98.7)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The p-value is for testing the proportion of participants achieving the mean serum phosphorus levels above the LLN (2.5 mg/dL [0.81 mmol/L]) against 0% from the binomial test.
Method binomial test
Comments [Not Specified]
3.Secondary Outcome
Title Percent Change From Baseline in O.Th at Week 48
Hide Description O.Th: mean thickness, given in micrometers, for osteoid seams.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: percentage change in thickness
-32.21  (11.966)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments The null hypothesis of no mean percent change from baseline is tested using t-test.
Method t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean
Estimated Value -32.21
Confidence Interval (2-Sided) 95%
-40.25 to -24.17
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Percent Change From Baseline in OS/BS at Week 48
Hide Description OS/Bs: percent of bone surface covered in osteoid.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: percent change of bone surface covered
-26.00  (15.012)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments The null hypothesis of no mean percent change from baseline is tested using t-test.
Method t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean
Estimated Value -26.00
Confidence Interval (2-Sided) 95%
-36.08 to -15.91
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Percent Change From Baseline in MLt at Week 48
Hide Description MLt: average time interval between osteoid formation and its subsequent mineralization; calculated by dividing the osteoid thickness by the adjusted apposition rate (O.Th/Aj.AR). Aj.AR; amount of new bone created (bone formation rate over the entire osteoid surface). Based on imputed MLt values.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percent change in average time interval
-52.24  (58.487)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0199
Comments The null hypothesis of no mean percent change from baseline is tested using t-test.
Method t-test
Comments [Not Specified]
Method of Estimation Estimation Parameter Mean
Estimated Value -52.24
Confidence Interval (2-Sided) 95%
-94.08 to -10.41
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change From Baseline in MAR at Week 48
Hide Description MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 11
Mean (Standard Deviation)
Unit of Measure: µm/day
0.04  (0.506)
7.Secondary Outcome
Title Change From Baseline in MS/BS at Week 48
Hide Description MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface ([dLS + sLS/2]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing data.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 10
Mean (Standard Deviation)
Unit of Measure: percent of mineralizing surface
1.32  (4.365)
8.Secondary Outcome
Title Change From Baseline in BFR/BS at Week 48
Hide Description

BFR/BS: amount of new bone formed in unit time per unit of bone surface; calculated by multiplying MS/BS by the MAR.

MS/BS: percent of bone surface that displays a tetracycline label reflecting active mineralization; calculated as the double-labeled surface plus one half of the single-labeled surface and is expressed as a function of total bone surface ([dLS + sLS/2]/BS). It is a measure of the proportion of bone surface upon which new mineralized bone was being deposited during the period of tetracycline labeling. MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.

Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: µm^3/µm^2/year
-4.90  (27.356)
9.Secondary Outcome
Title Change From Baseline in BFR/OS at Week 48
Hide Description BFR/OS: bone formation rate to osteoid surface ratio, related to the Aj.AR (amount of new bone created [bone formation rate over the entire osteoid surface]).
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 4
Mean (Standard Deviation)
Unit of Measure: µm^3/µm^2/year
-1557.25  (3139.075)
10.Secondary Outcome
Title Change From Baseline in BFR/BV at Week 48
Hide Description BFR/BV: equivalent to bone turnover rate.
Time Frame Baseline, 48 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 6
Mean (Standard Deviation)
Unit of Measure: percentage of bone turnover/year
-13.50  (32.904)
11.Secondary Outcome
Title Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle Between Baseline and Week 24
Hide Description The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% CI was calculated using Wilson score method.
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: percentage of participants
78.6
(52.4 to 92.4)
12.Secondary Outcome
Title Mean Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
1.07  (0.300)
13.Secondary Outcome
Title Percent Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percent change of serum phosphorus level
50.39  (19.942)
14.Secondary Outcome
Title Mean Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
0.46  (0.303)
15.Secondary Outcome
Title Percentage Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: percent change of serum phosphorus level
23.32  (19.836)
16.Secondary Outcome
Title Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
Hide Description [Not Specified]
Time Frame Baseline, up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: mg/dL
3.023  (0.2716)
17.Secondary Outcome
Title Change From Baseline Over Time in Serum 1,25(OH)2D
Hide Description [Not Specified]
Time Frame Baseline, Week 1, Week 2, Week 4, Week 20, Week 21, Week 22, Week 24, Week 48, Week 60, Week 70, Week 72, Week 84, Week 94, Week 96, Week 108, Week 120, Week 132
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 12
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 1 Number Analyzed 12 participants
107.75  (15.964)
Week 2 Number Analyzed 12 participants
48.41  (7.397)
Week 4 Number Analyzed 12 participants
13.58  (3.435)
Week 20 Number Analyzed 12 participants
-1.34  (3.617)
Week 21 Number Analyzed 12 participants
31.75  (5.233)
Week 22 Number Analyzed 11 participants
11.50  (4.060)
Week 24 Number Analyzed 8 participants
-3.04  (4.891)
Week 48 Number Analyzed 11 participants
-1.72  (4.190)
Week 60 Number Analyzed 11 participants
-5.73  (3.395)
Week 70 Number Analyzed 11 participants
3.36  (3.987)
Week 72 Number Analyzed 11 participants
-5.55  (2.895)
Week 84 Number Analyzed 11 participants
-5.55  (2.962)
Week 94 Number Analyzed 11 participants
9.63  (4.239)
Week 96 Number Analyzed 11 participants
-6.09  (2.403)
Week 108 Number Analyzed 7 participants
0.02  (4.714)
Week 120 Number Analyzed 2 participants
1.45  (4.197)
Week 132 Number Analyzed 1 participants
-1.69  (1.993)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 1
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter Least Squares Mean (GEE)
Estimated Value 107.75
Confidence Interval (2-Sided) 95%
76.46 to 139.03
Estimation Comments From the generalized estimation equation (GEE) model which includes change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 48.41
Confidence Interval (2-Sided) 95%
33.91 to 62.91
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 13.58
Confidence Interval (2-Sided) 95%
6.85 to 20.31
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 20
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -1.34
Confidence Interval (2-Sided) 95%
-8.43 to 5.75
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 21
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 31.75
Confidence Interval (2-Sided) 95%
21.49 to 42.00
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 22
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 11.50
Confidence Interval (2-Sided) 95%
3.54 to 19.46
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -3.04
Confidence Interval (2-Sided) 95%
-12.62 to 6.55
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6821
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -1.72
Confidence Interval (2-Sided) 95%
-9.93 to 6.50
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 60
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -5.73
Confidence Interval (2-Sided) 95%
-12.38 to 0.92
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 70
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 3.36
Confidence Interval (2-Sided) 95%
-4.45 to 11.18
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -5.55
Confidence Interval (2-Sided) 95%
-11.22 to 0.13
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 12
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 84
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -5.55
Confidence Interval (2-Sided) 95%
-11.35 to 0.26
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 13
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 94
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 9.63
Confidence Interval (2-Sided) 95%
1.33 to 17.94
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 14
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -6.09
Confidence Interval (2-Sided) 95%
-10.80 to -1.38
Estimation Comments [Not Specified]
Hide Statistical Analysis 15
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 108
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-9.22 to 9.26
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 16
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 120
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.45
Confidence Interval (2-Sided) 95%
-6.77 to 9.68
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 17
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 132
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -1.69
Confidence Interval (2-Sided) 95%
-5.60 to 2.21
Estimation Comments From the GEE model which includes the change from baseline for 1, 25 (OH)2 D as the dependent variable, visit as fixed factors, and baseline of 1, 25 (OH)2 D as a covariate, with compound symmetry covariance structure.
18.Secondary Outcome
Title Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Hide Description [Not Specified]
Time Frame Baseline, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96, End of Study II (EOSII) (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 12
Least Squares Mean (Standard Error)
Unit of Measure: g/24 hours
Week 12 Number Analyzed 11 participants
0.10  (0.128)
Week 24 Number Analyzed 12 participants
-0.04  (0.075)
Week 36 Number Analyzed 12 participants
-0.01  (0.059)
Week 48 Number Analyzed 11 participants
-0.04  (0.076)
Week 72 Number Analyzed 11 participants
0.00  (0.096)
Week 96 Number Analyzed 9 participants
-0.13  (0.082)
EOSII Number Analyzed 5 participants
-0.07  (0.171)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.10
Confidence Interval (2-Sided) 95%
-0.15 to 0.35
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.19 to 0.11
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 36
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.01
Confidence Interval (2-Sided) 95%
-0.12 to 0.11
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6021
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.04
Confidence Interval (2-Sided) 95%
-0.19 to 0.11
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.00
Confidence Interval (2-Sided) 95%
-0.19 to 0.19
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.13
Confidence Interval (2-Sided) 95%
-0.29 to 0.03
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOS II
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.07
Confidence Interval (2-Sided) 95%
-0.41 to 0.26
Estimation Comments From the GEE model; includes change from baseline from baseline for 24-Hour urinary phosphorus as the dependent variable, visit as fixed factors, and baseline of 24-Hour urinary phosphorus as a covariate, with compound symmetry covariance structure.
19.Secondary Outcome
Title Change From Baseline Over Time in TmP/GFR
Hide Description TmP/GFR: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate.
Time Frame Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: mg/dL
Week 2 Number Analyzed 13 participants
1.76  (0.136)
Week 4 Number Analyzed 13 participants
0.78  (0.097)
Week 12 Number Analyzed 13 participants
0.58  (0.122)
Week 22 Number Analyzed 13 participants
0.87  (0.064)
Week 24 Number Analyzed 13 participants
0.44  (0.101)
Week 48 Number Analyzed 13 participants
0.20  (0.097)
Week 60 Number Analyzed 13 participants
0.30  (0.171)
Week 72 Number Analyzed 12 participants
0.28  (0.127)
Week 84 Number Analyzed 13 participants
0.39  (0.136)
Week 96 Number Analyzed 13 participants
0.29  (0.097)
EOSII Number Analyzed 8 participants
0.21  (0.068)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 1.76
Confidence Interval (2-Sided) 95%
1.49 to 2.03
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.78
Confidence Interval (2-Sided) 95%
0.59 to 0.97
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.58
Confidence Interval (2-Sided) 95%
0.34 to 0.82
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 22
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.74 to 0.99
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.44
Confidence Interval (2-Sided) 95%
0.24 to 0.64
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0430
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.20
Confidence Interval (2-Sided) 95%
0.01 to 0.38
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 60
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
-0.04 to 0.64
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.28
Confidence Interval (2-Sided) 95%
0.03 to 0.52
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 84
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.39
Confidence Interval (2-Sided) 95%
0.13 to 0.66
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.29
Confidence Interval (2-Sided) 95%
0.10 to 0.48
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.21
Confidence Interval (2-Sided) 95%
0.08 to 0.34
Estimation Comments From the GEE model, which includes the change from baseline for TmP/GFR as the dependent variable, visit as fixed factors, and baseline of TmP/GFR as a covariate, with compound symmetry covariance structure.
20.Secondary Outcome
Title Change From Baseline Over Time in TRP
Hide Description TRP: tubular reabsorption of phosphate.
Time Frame Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: fraction of phosphorus reabsorbed
Week 2 Number Analyzed 14 participants
0.07  (0.005)
Week 4 Number Analyzed 14 participants
0.03  (0.013)
Week 12 Number Analyzed 13 participants
0.01  (0.013)
Week 22 Number Analyzed 12 participants
0.04  (0.007)
Week 24 Number Analyzed 14 participants
0.01  (0.015)
Week 48 Number Analyzed 13 participants
-0.00  (0.021)
Week 60 Number Analyzed 13 participants
0.03  (0.016)
Week 72 Number Analyzed 13 participants
-0.02  (0.035)
Week 84 Number Analyzed 13 participants
0.02  (0.019)
Week 96 Number Analyzed 13 participants
0.02  (0.014)
EOSII Number Analyzed 8 participants
0.01  (0.011)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 2
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.07
Confidence Interval (2-Sided) 95%
0.06 to 0.08
Estimation Comments From the GEE model, which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 4
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
0.01 to 0.06
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
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 From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 22
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.04
Confidence Interval (2-Sided) 95%
0.02 to 0.05
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 0.01
Confidence Interval (2-Sided) 95%
-0.02 to 0.04
Estimation Comments [Not Specified]
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8377
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value -0.00
Confidence Interval (2-Sided) 95%
-0.05 to 0.04
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 7
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 60
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.03
Confidence Interval (2-Sided) 95%
-0.00 to 0.06
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 8
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -0.02
Confidence Interval (2-Sided) 95%
-0.09 to 0.05
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 9
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 84
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 0.02
Confidence Interval (2-Sided) 95%
-0.01 to 0.06
Estimation Comments From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 10
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
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 From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 11
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
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 From the GEE model which includes the change from baseline or percent change from baseline for TRP as the dependent variable, visit as fixed factors, and baseline of TRP as a covariate, with compound symmetry covariance structure.
21.Secondary Outcome
Title Change From Baseline Over Time in P1NP
Hide Description P1NP: procollagen type 1 N-propeptide.
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: ng/mL
Week 12 Number Analyzed 13 participants
99.18  (11.403)
Week 24 Number Analyzed 14 participants
104.33  (11.153)
Week 48 Number Analyzed 13 participants
52.49  (11.554)
Week 72 Number Analyzed 13 participants
37.29  (12.294)
Week 96 Number Analyzed 13 participants
29.29  (13.321)
EOSII Number Analyzed 8 participants
2.14  (10.105)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 99.18
Confidence Interval (2-Sided) 95%
76.83 to 121.53
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 104.33
Confidence Interval (2-Sided) 95%
82.47 to 126.19
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 52.49
Confidence Interval (2-Sided) 95%
29.84 to 75.13
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 37.29
Confidence Interval (2-Sided) 95%
13.19 to 61.38
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 29.29
Confidence Interval (2-Sided) 95%
3.18 to 55.40
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 2.14
Confidence Interval (2-Sided) 95%
-17.67 to 21.94
Estimation Comments From the GEE model, which includes the change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
22.Secondary Outcome
Title Percent Change From Baseline Over Time in P1NP
Hide Description [Not Specified]
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change in P1NP
Week 12 Number Analyzed 13 participants
133.08  (13.680)
Week 24 Number Analyzed 14 participants
137.80  (15.741)
Week 48 Number Analyzed 13 participants
76.86  (14.114)
Week 72 Number Analyzed 13 participants
50.46  (13.659)
Week 96 Number Analyzed 13 participants
41.36  (11.566)
EOSII Number Analyzed 8 participants
26.20  (9.919)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 133.08
Confidence Interval (2-Sided) 95%
106.26 to 159.89
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 137.80
Confidence Interval (2-Sided) 95%
106.95 to 168.65
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 76.86
Confidence Interval (2-Sided) 95%
49.20 to 104.53
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 50.46
Confidence Interval (2-Sided) 95%
23.69 to 77.23
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 41.36
Confidence Interval (2-Sided) 95%
18.69 to 64.03
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 26.20
Confidence Interval (2-Sided) 95%
6.76 to 45.64
Estimation Comments From the GEE model, which includes the percent change from baseline for P1NP as the dependent variable, visit as fixed factors, and baseline of P1NP as a covariate, with compound symmetry covariance structure.
23.Secondary Outcome
Title Change From Baseline Over Time in CTx
Hide Description CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: pg/mL
Week 12 Number Analyzed 14 participants
464.84  (61.696)
Week 24 Number Analyzed 14 participants
404.13  (55.948)
Week 48 Number Analyzed 13 participants
175.13  (44.022)
Week 72 Number Analyzed 13 participants
143.11  (92.503)
Week 96 Number Analyzed 13 participants
76.80  (57.357)
EOSII Number Analyzed 8 participants
-41.32  (83.144)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 464.84
Confidence Interval (2-Sided) 95%
343.92 to 585.77
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 404.13
Confidence Interval (2-Sided) 95%
294.47 to 513.78
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 175.13
Confidence Interval (2-Sided) 95%
88.85 to 261.41
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 143.11
Confidence Interval (2-Sided) 95%
-38.20 to 324.41
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 76.80
Confidence Interval (2-Sided) 95%
-35.62 to 189.22
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -41.32
Confidence Interval (2-Sided) 95%
-204.28 to 121.64
Estimation Comments From the GEE model which includes the change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
24.Secondary Outcome
Title Percent Change From Baseline Over Time in CTx
Hide Description CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 14
Least Squares Mean (Standard Error)
Unit of Measure: percent change in CTx
Week 12 Number Analyzed 14 participants
89.68  (13.316)
Week 24 Number Analyzed 14 participants
70.17  (10.341)
Week 48 Number Analyzed 13 participants
35.86  (7.396)
Week 72 Number Analyzed 13 participants
34.00  (14.016)
Week 96 Number Analyzed 13 participants
25.86  (8.461)
EOSII Number Analyzed 8 participants
17.88  (9.284)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 89.68
Confidence Interval (2-Sided) 95%
63.58 to 115.78
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 70.17
Confidence Interval (2-Sided) 95%
49.90 to 90.44
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value < 0.0001
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 35.86
Confidence Interval (2-Sided) 95%
21.37 to 50.36
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 34.00
Confidence Interval (2-Sided) 95%
6.53 to 61.47
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 25.86
Confidence Interval (2-Sided) 95%
9.27 to 42.44
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 17.88
Confidence Interval (2-Sided) 95%
-0.32 to 36.07
Estimation Comments From the GEE model which includes the percent change from baseline for CTx as the dependent variable, visit as fixed factors, and baseline of CTx as a covariate, with compound symmetry covariance structure.
25.Secondary Outcome
Title Change From Baseline Over Time in BALP
Hide Description BALP: bone-specific alkaline phosphatase.
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: μg/L
Week 12 Number Analyzed 13 participants
10.93  (3.547)
Week 24 Number Analyzed 13 participants
5.82  (2.980)
Week 48 Number Analyzed 13 participants
4.50  (3.990)
Week 72 Number Analyzed 12 participants
3.13  (2.435)
Week 96 Number Analyzed 13 participants
1.14  (2.028)
EOSII Number Analyzed 8 participants
-5.80  (3.396)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 10.93
Confidence Interval (2-Sided) 95%
3.98 to 17.89
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 5.82
Confidence Interval (2-Sided) 95%
-0.02 to 11.66
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2592
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 4.50
Confidence Interval (2-Sided) 95%
-3.32 to 12.32
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 3.13
Confidence Interval (2-Sided) 95%
-1.64 to 7.90
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 1.14
Confidence Interval (2-Sided) 95%
-2.84 to 5.11
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -5.80
Confidence Interval (2-Sided) 95%
-12.46 to 0.85
Estimation Comments From the GEE model, which includes the change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
26.Secondary Outcome
Title Percent Change From Baseline Over Time in BALP
Hide Description BALP: bone-specific alkaline phosphatase.
Time Frame Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description:
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
Overall Number of Participants Analyzed 13
Least Squares Mean (Standard Error)
Unit of Measure: percent change in BALP
Week 12 Number Analyzed 13 participants
52.54  (15.999)
Week 24 Number Analyzed 13 participants
31.37  (11.808)
Week 48 Number Analyzed 13 participants
24.35  (17.630)
Week 72 Number Analyzed 12 participants
15.13  (13.431)
Week 96 Number Analyzed 13 participants
6.92  (10.387)
EOSII Number Analyzed 8 participants
-27.30  (12.767)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 12
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 52.54
Confidence Interval (2-Sided) 95%
21.18 to 83.90
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 24
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS Mean
Estimated Value 31.37
Confidence Interval (2-Sided) 95%
8.23 to 54.51
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 48
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1672
Comments [Not Specified]
Method GEE model
Comments [Not Specified]
Method of Estimation Estimation Parameter l
Estimated Value 24.35
Confidence Interval (2-Sided) 95%
-10.20 to 58.90
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 72
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 15.13
Confidence Interval (2-Sided) 95%
-11.19 to 41.46
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 5
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments Week 96
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value 6.92
Confidence Interval (2-Sided) 95%
-13.44 to 27.28
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Hide Statistical Analysis 6
Statistical Analysis Overview Comparison Group Selection Open-Label Burosumab Q4W
Comments EOSII
Type of Statistical Test Other
Comments [Not Specified]
Method of Estimation Estimation Parameter LS mean
Estimated Value -27.30
Confidence Interval (2-Sided) 95%
-52.33 to -2.28
Estimation Comments From the GEE model, which includes the percent change from baseline for Bone ALP as the dependent variable, visit as fixed factors, and baseline of Bone ALP as a covariate, with compound symmetry covariance structure.
Time Frame Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Adverse Event Reporting Description Treatment-emergent adverse events are presented.
 
Arm/Group Title Open-Label Burosumab Q4W
Hide Arm/Group Description 1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
All-Cause Mortality
Open-Label Burosumab Q4W
Affected / at Risk (%)
Total   0/14 (0.00%) 
Hide Serious Adverse Events
Open-Label Burosumab Q4W
Affected / at Risk (%)
Total   4/14 (28.57%) 
Cardiac disorders   
Atrial Fibrillation  1  1/14 (7.14%) 
Gastrointestinal disorders   
Obstruction Gastric  1  1/14 (7.14%) 
Injury, poisoning and procedural complications   
Splenic Rupture  1  1/14 (7.14%) 
Nervous system disorders   
Migraine  1  1/14 (7.14%) 
Paraesthesia  1  1/14 (7.14%) 
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%
Open-Label Burosumab Q4W
Affected / at Risk (%)
Total   14/14 (100.00%) 
Cardiac disorders   
Bradycardia  1  1/14 (7.14%) 
Pericarditis  1  1/14 (7.14%) 
Ear and labyrinth disorders   
Hypoacusis  1  1/14 (7.14%) 
Gastrointestinal disorders   
Abdominal Discomfort  1  2/14 (14.29%) 
Abdominal Distension  1  1/14 (7.14%) 
Abdominal Pain  1  3/14 (21.43%) 
Abdominal Pain Upper  1  3/14 (21.43%) 
Constipation  1  3/14 (21.43%) 
Diarrhoea  1  2/14 (14.29%) 
Dyspepsia  1  1/14 (7.14%) 
Gastrooesophageal Reflux Disease  1  2/14 (14.29%) 
Gingival Pain  1  1/14 (7.14%) 
Gingival Swelling  1  2/14 (14.29%) 
Irritable Bowel Syndrome  1  1/14 (7.14%) 
Mouth Ulceration  1  1/14 (7.14%) 
Nausea  1  2/14 (14.29%) 
Oral Pain  1  1/14 (7.14%) 
Periodontal Disease  1  1/14 (7.14%) 
Toothache  1  4/14 (28.57%) 
Vomiting  1  2/14 (14.29%) 
Vomiting Projectile  1  1/14 (7.14%) 
General disorders   
Application Site Rash  1  1/14 (7.14%) 
Asthenia  1  2/14 (14.29%) 
Chest Discomfort  1  2/14 (14.29%) 
Chest Pain  1  1/14 (7.14%) 
Drug Withdrawal Syndrome  1  1/14 (7.14%) 
Fatigue  1  3/14 (21.43%) 
Influenza Like Illness  1  2/14 (14.29%) 
Injection Site Bruising  1  1/14 (7.14%) 
Injection Site Pain  1  2/14 (14.29%) 
Injection Site Pruritus  1  1/14 (7.14%) 
Injection Site Reaction  1  2/14 (14.29%) 
Injection Site Urticaria  1  3/14 (21.43%) 
Local Swelling  1  1/14 (7.14%) 
Nodule  1  1/14 (7.14%) 
Non-Cardiac Chest Pain  1  1/14 (7.14%) 
Oedema Peripheral  1  1/14 (7.14%) 
Pain  1  5/14 (35.71%) 
Peripheral Swelling  1  1/14 (7.14%) 
Pyrexia  1  1/14 (7.14%) 
Hepatobiliary disorders   
Hepatic Steatosis  1  1/14 (7.14%) 
Immune system disorders   
Drug Hypersensitivity  1  2/14 (14.29%) 
Seasonal Allergy  1  1/14 (7.14%) 
Infections and infestations   
Bronchitis  1  1/14 (7.14%) 
Conjunctivitis Bacterial  1  1/14 (7.14%) 
Gingival Abscess  1  1/14 (7.14%) 
Gingivitis  1  1/14 (7.14%) 
Hordeolum  1  1/14 (7.14%) 
Influenza  1  4/14 (28.57%) 
Laryngitis  1  1/14 (7.14%) 
Lice Infestation  1  1/14 (7.14%) 
Lung Infection  1  1/14 (7.14%) 
Nasopharyngitis  1  4/14 (28.57%) 
Periodontitis  1  1/14 (7.14%) 
Pharyngitis  1  1/14 (7.14%) 
Pharyngitis Streptococcal  1  2/14 (14.29%) 
Postoperative Wound Infection  1  1/14 (7.14%) 
Respiratory Tract Infection Viral  1  1/14 (7.14%) 
Root Canal Infection  1  1/14 (7.14%) 
Sinusitis  1  2/14 (14.29%) 
Tooth Abscess  1  7/14 (50.00%) 
Tooth Infection  1  1/14 (7.14%) 
Upper Respiratory Tract Infection  1  2/14 (14.29%) 
Urinary Tract Infection  1  2/14 (14.29%) 
Vulvovaginal Mycotic Infection  1  1/14 (7.14%) 
Injury, poisoning and procedural complications   
Concussion  1  1/14 (7.14%) 
Contusion  1  1/14 (7.14%) 
Fall  1  3/14 (21.43%) 
Incision Site Pruritus  1  2/14 (14.29%) 
Injection Related Reaction  1  1/14 (7.14%) 
Ligament Sprain  1  1/14 (7.14%) 
Post Procedural Swelling  1  1/14 (7.14%) 
Procedural Pain  1  7/14 (50.00%) 
Stress Fracture  1  1/14 (7.14%) 
Sunburn  1  1/14 (7.14%) 
Tooth Fracture  1  2/14 (14.29%) 
Tooth Injury  1  1/14 (7.14%) 
Investigations   
Blood 25-Hydroxycholecalciferol Decreased  1  2/14 (14.29%) 
Blood Calcium Decreased  1  1/14 (7.14%) 
Blood Cholesterol Increased  1  1/14 (7.14%) 
Blood Glucose Increased  1  1/14 (7.14%) 
Blood Parathyroid Hormone Increased  1  1/14 (7.14%) 
Blood Pressure Increased  1  1/14 (7.14%) 
Blood Testosterone Decreased  1  1/14 (7.14%) 
Blood Uric Acid Increased  1  1/14 (7.14%) 
Ejection Fraction Decreased  1  1/14 (7.14%) 
Eosinophil Count Increased  1  1/14 (7.14%) 
Ultrasound Kidney Abnormal  1  1/14 (7.14%) 
Vitamin D Decreased  1  1/14 (7.14%) 
Metabolism and nutrition disorders   
Hyperuricaemia  1  1/14 (7.14%) 
Hypocalcaemia  1  1/14 (7.14%) 
Vitamin D Deficiency  1  2/14 (14.29%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  5/14 (35.71%) 
Arthritis  1  1/14 (7.14%) 
Back Pain  1  6/14 (42.86%) 
Bone Pain  1  3/14 (21.43%) 
Fibromyalgia  1  1/14 (7.14%) 
Joint Instability  1  1/14 (7.14%) 
Joint Swelling  1  2/14 (14.29%) 
Limb Discomfort  1  1/14 (7.14%) 
Muscle Atrophy  1  2/14 (14.29%) 
Muscle Spasms  1  4/14 (28.57%) 
Muscular Weakness  1  1/14 (7.14%) 
Musculoskeletal Chest Pain  1  2/14 (14.29%) 
Musculoskeletal Pain  1  1/14 (7.14%) 
Musculoskeletal Stiffness  1  1/14 (7.14%) 
Neck Pain  1  1/14 (7.14%) 
Osteoarthritis  1  4/14 (28.57%) 
Pain In Extremity  1  4/14 (28.57%) 
Pain In Jaw  1  1/14 (7.14%) 
Spinal Pain  1  2/14 (14.29%) 
Tendonitis  1  1/14 (7.14%) 
Nervous system disorders   
Amnesia  1  1/14 (7.14%) 
Dizziness  1  3/14 (21.43%) 
Dysaesthesia  1  1/14 (7.14%) 
Headache  1  2/14 (14.29%) 
Hypoaesthesia  1  3/14 (21.43%) 
Migraine  1  1/14 (7.14%) 
Motor Dysfunction  1  1/14 (7.14%) 
Nerve Compression  1  1/14 (7.14%) 
Neuralgia  1  1/14 (7.14%) 
Paraesthesia  1  3/14 (21.43%) 
Restless Legs Syndrome  1  1/14 (7.14%) 
Sciatica  1  1/14 (7.14%) 
Somnolence  1  1/14 (7.14%) 
Syncope  1  1/14 (7.14%) 
Tremor  1  1/14 (7.14%) 
Psychiatric disorders   
Anxiety  1  4/14 (28.57%) 
Confusional State  1  1/14 (7.14%) 
Depression  1  2/14 (14.29%) 
Depressive Symptom  1  1/14 (7.14%) 
Insomnia  1  3/14 (21.43%) 
Irritability  1  1/14 (7.14%) 
Nightmare  1  1/14 (7.14%) 
Renal and urinary disorders   
Glycosuria  1  1/14 (7.14%) 
Urinary Retention  1  1/14 (7.14%) 
Reproductive system and breast disorders   
Dysmenorrhoea  1  1/14 (7.14%) 
Ovarian Cyst  1  1/14 (7.14%) 
Uterine Haemorrhage  1  1/14 (7.14%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  3/14 (21.43%) 
Nasal Congestion  1  2/14 (14.29%) 
Oropharyngeal Pain  1  2/14 (14.29%) 
Productive Cough  1  1/14 (7.14%) 
Respiratory Tract Congestion  1  1/14 (7.14%) 
Sinus Congestion  1  4/14 (28.57%) 
Sinus Perforation  1  1/14 (7.14%) 
Skin and subcutaneous tissue disorders   
Dermatitis  1  1/14 (7.14%) 
Eczema  1  1/14 (7.14%) 
Hyperhidrosis  1  1/14 (7.14%) 
Pruritus Generalised  1  1/14 (7.14%) 
Rash  1  2/14 (14.29%) 
Skin Irritation  1  1/14 (7.14%) 
Urticaria  1  1/14 (7.14%) 
Xanthoma  1  2/14 (14.29%) 
Vascular disorders   
Hot Flush  1  1/14 (7.14%) 
Hypertension  1  2/14 (14.29%) 
1
Term from vocabulary, MedDRA 18.1
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days from the time submitted to the sponsor for review. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Medical Information
Organization: Ultragenyx Pharmaceutical Inc
Phone: 1-888-756-8657
EMail: Medinfo@ultragenyx.com
Layout table for additonal information
Responsible Party: Ultragenyx Pharmaceutical Inc
ClinicalTrials.gov Identifier: NCT02537431    
Other Study ID Numbers: UX023-CL304
First Submitted: August 25, 2015
First Posted: September 1, 2015
Results First Submitted: August 27, 2018
Results First Posted: September 25, 2018
Last Update Posted: December 23, 2019