Trial Outcomes & Findings for Open Label Study of KRN23 on Osteomalacia in Adults With X-linked Hypophosphatemia (XLH) (NCT NCT02537431)
NCT ID: NCT02537431
Last Updated: 2024-06-18
Results Overview
OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
14 participants
Primary outcome timeframe
Baseline, 48 weeks
Results posted on
2024-06-18
Participant Flow
Participant milestones
| Measure |
Open-Label Burosumab Q4W
1.0 mg/kg burosumab monthly (Q4W), calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Open-Label Period (Week 0 to Week 48)
STARTED
|
14
|
|
Open-Label Period (Week 0 to Week 48)
COMPLETED
|
13
|
|
Open-Label Period (Week 0 to Week 48)
NOT COMPLETED
|
1
|
|
Treatment Extension Period I
STARTED
|
13
|
|
Treatment Extension Period I
COMPLETED
|
13
|
|
Treatment Extension Period I
NOT COMPLETED
|
0
|
|
Treatment Extension Period II
STARTED
|
8
|
|
Treatment Extension Period II
COMPLETED
|
8
|
|
Treatment Extension Period II
NOT COMPLETED
|
0
|
Reasons for withdrawal
| Measure |
Open-Label Burosumab Q4W
1.0 mg/kg burosumab monthly (Q4W), calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Open-Label Period (Week 0 to Week 48)
Withdrawal by Subject
|
1
|
Baseline Characteristics
Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
Baseline characteristics by cohort
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Age, Continuous
|
40.13 years
STANDARD_DEVIATION 8.725 • n=14 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=14 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=14 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=14 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
13 Participants
n=14 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=14 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=14 Participants
|
|
Race (NIH/OMB)
Asian
|
4 Participants
n=14 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=14 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=14 Participants
|
|
Race (NIH/OMB)
White
|
9 Participants
n=14 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=14 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=14 Participants
|
|
Osteoid Volume/Bone Volume (OV/BV)
|
26.12 percentage of osteoid volume
STANDARD_DEVIATION 12.357 • n=10 Participants • 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
|
2.24 mg/dL
STANDARD_DEVIATION 0.396 • n=14 Participants
|
|
Osteoid Thickness (O.Th)
|
17.21 µm
STANDARD_DEVIATION 4.105 • n=11 Participants • Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
|
|
Osteoid Surface/Bone Surface (OS/BS)
|
91.73 percentage of osteoid surface
STANDARD_DEVIATION 3.438 • n=11 Participants • Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
|
|
Mineralization Lag Time (MLt)
|
1539.81 days
STANDARD_DEVIATION 1587.086 • n=11 Participants • Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
|
|
Mineral Apposition Rate (MAR)
|
0.58 µm/day
STANDARD_DEVIATION 0.448 • n=11 Participants • Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data.
|
|
Mineralizing Surface/Bone Surface (MS/BS)
|
5.99 percentage of mineralizing surface
STANDARD_DEVIATION 4.763 • n=11 Participants • 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)
|
26.68 µm^3/µm^2/year
STANDARD_DEVIATION 19.480 • n=6 Participants • 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)
|
2309.00 µm^3/µm^2/year
STANDARD_DEVIATION 2941.970 • n=4 Participants • 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)
|
38.33 percent/year
STANDARD_DEVIATION 37.173 • n=6 Participants • 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
|
37.25 pg/mL
STANDARD_DEVIATION 11.686 • n=12 Participants • Full Analysis Set: enrolled and dosed participants with a baseline measurement.
|
|
24-Hour Urinary Phosphorus
|
0.82 g/24hr
STANDARD_DEVIATION 0.237 • n=12 Participants • 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)
|
1.87 mg/dL
STANDARD_DEVIATION 0.307 • n=14 Participants
|
|
Tubular Reabsorption of Phosphate (TRP)
|
0.84 fraction of phosphorus reabsorbed
STANDARD_DEVIATION 0.048 • n=14 Participants
|
|
Procollagen Type 1 N-Propeptide (P1NP)
|
77.00 ng/mL
STANDARD_DEVIATION 33.273 • n=14 Participants
|
|
Carboxy-Terminal Cross-Linked Telopeptide of Type I Collagen (CTx-I)
|
646.93 pg/mL
STANDARD_DEVIATION 401.641 • n=14 Participants
|
|
Bone-Specific Alkaline Phosphatase (BALP)
|
20.43 μg/L
STANDARD_DEVIATION 9.288 • n=14 Participants
|
|
Mineralizing Surface/OsteoidSurface (MS/OS)
|
6.47 percentage of mineralizing surface
STANDARD_DEVIATION 5.120 • n=11 Participants • Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
|
PRIMARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
OV/BV: percent of a given volume of bone tissue that consists of unmineralized bone (osteoid).
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=10 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline in OV/BV at Week 48
|
-54.18 percentage change of unmineralized bone
Standard Deviation 20.211
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% confidence interval (CI) was calculated using Wilson score method.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the Lower Limit of Normal (LLN) at the Mid-Point of the Dose Interval, as Averaged Across Dose Cycles Between Baseline and Week 24
|
92.9 percentage of participants
Interval 68.5 to 98.7
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
O.Th: mean thickness, given in micrometers, for osteoid seams.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=11 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline in O.Th at Week 48
|
-32.21 percentage change in thickness
Standard Deviation 11.966
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
OS/Bs: percent of bone surface covered in osteoid.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=11 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline in OS/BS at Week 48
|
-26.00 percent change of bone surface covered
Standard Deviation 15.012
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
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.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=10 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline in MLt at Week 48
|
-52.24 percent change in average time interval
Standard Deviation 58.487
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing results.
MAR: linear rate of new bone deposition; mean distance between the double labels, divided by the time interval between them.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=11 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline in MAR at Week 48
|
0.04 µm/day
Standard Deviation 0.506
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data who had non-missing data.
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.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=10 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline in MS/BS at Week 48
|
1.32 percent of mineralizing surface
Standard Deviation 4.365
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
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.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=6 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline in BFR/BS at Week 48
|
-4.90 µm^3/µm^2/year
Standard Deviation 27.356
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
BFR/OS: bone formation rate to osteoid surface ratio, related to the Aj.AR (amount of new bone created \[bone formation rate over the entire osteoid surface\]).
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=4 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline in BFR/OS at Week 48
|
-1557.25 µm^3/µm^2/year
Standard Deviation 3139.075
|
SECONDARY outcome
Timeframe: Baseline, 48 weeksPopulation: Primary Analysis Set: enrolled participants with baseline and follow-up (Week 48/end of treatment) bone biopsy data; participants with non-missing results.
BFR/BV: equivalent to bone turnover rate.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=6 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline in BFR/BV at Week 48
|
-13.50 percentage of bone turnover/year
Standard Deviation 32.904
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
The LLN was defined as 2.5 mg/dL (0.81 mmol/L). The 95% CI was calculated using Wilson score method.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percentage of Participants Achieving Mean Serum Phosphorus Levels Above the LLN at the End of the Dosing Cycle Between Baseline and Week 24
|
78.6 percentage of participants
Interval 52.4 to 92.4
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Mean Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
|
1.07 mg/dL
Standard Deviation 0.300
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change of Serum Phosphorus Levels at the Mid-Point of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
|
50.39 percent change of serum phosphorus level
Standard Deviation 19.942
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Mean Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
|
0.46 mg/dL
Standard Deviation 0.303
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percentage Change of Serum Phosphorus Levels at the End of Dosing Cycle, as Averaged Across Dose Cycles Between Baseline and Week 24
|
23.32 percent change of serum phosphorus level
Standard Deviation 19.836
|
SECONDARY outcome
Timeframe: Baseline, up to 24 weeksPopulation: Full Analysis Set: all enrolled participants who receive at least one dose of study drug.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Time-Adjusted Area Under the Curve (AUC) of Serum Phosphorus Between Baseline and Week 24
|
3.023 mg/dL
Standard Deviation 0.2716
|
SECONDARY outcome
Timeframe: 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 132Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=12 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 1
|
107.75 pg/mL
Standard Error 15.964
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 2
|
48.41 pg/mL
Standard Error 7.397
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 4
|
13.58 pg/mL
Standard Error 3.435
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 20
|
-1.34 pg/mL
Standard Error 3.617
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 21
|
31.75 pg/mL
Standard Error 5.233
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 22
|
11.50 pg/mL
Standard Error 4.060
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 24
|
-3.04 pg/mL
Standard Error 4.891
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 48
|
-1.72 pg/mL
Standard Error 4.190
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 60
|
-5.73 pg/mL
Standard Error 3.395
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 70
|
3.36 pg/mL
Standard Error 3.987
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 72
|
-5.55 pg/mL
Standard Error 2.895
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 84
|
-5.55 pg/mL
Standard Error 2.962
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 94
|
9.63 pg/mL
Standard Error 4.239
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 96
|
-6.09 pg/mL
Standard Error 2.403
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 108
|
0.02 pg/mL
Standard Error 4.714
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 120
|
1.45 pg/mL
Standard Error 4.197
|
|
Change From Baseline Over Time in Serum 1,25(OH)2D
Week 132
|
-1.69 pg/mL
Standard Error 1.993
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 36, Week 48, Week 72, Week 96, End of Study II (EOSII) (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=12 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 12
|
0.10 g/24 hours
Standard Error 0.128
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 24
|
-0.04 g/24 hours
Standard Error 0.075
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 36
|
-0.01 g/24 hours
Standard Error 0.059
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 48
|
-0.04 g/24 hours
Standard Error 0.076
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 72
|
0.00 g/24 hours
Standard Error 0.096
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
Week 96
|
-0.13 g/24 hours
Standard Error 0.082
|
|
Change From Baseline Over Time in 24-Hour Urinary Phosphorus
EOSII
|
-0.07 g/24 hours
Standard Error 0.171
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
TmP/GFR: ratio of renal tubular maximum reabsorption rate of phosphate to glomerular filtration rate.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=13 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in TmP/GFR
Week 2
|
1.76 mg/dL
Standard Error 0.136
|
|
Change From Baseline Over Time in TmP/GFR
Week 4
|
0.78 mg/dL
Standard Error 0.097
|
|
Change From Baseline Over Time in TmP/GFR
Week 12
|
0.58 mg/dL
Standard Error 0.122
|
|
Change From Baseline Over Time in TmP/GFR
Week 22
|
0.87 mg/dL
Standard Error 0.064
|
|
Change From Baseline Over Time in TmP/GFR
Week 24
|
0.44 mg/dL
Standard Error 0.101
|
|
Change From Baseline Over Time in TmP/GFR
Week 48
|
0.20 mg/dL
Standard Error 0.097
|
|
Change From Baseline Over Time in TmP/GFR
Week 60
|
0.30 mg/dL
Standard Error 0.171
|
|
Change From Baseline Over Time in TmP/GFR
Week 72
|
0.28 mg/dL
Standard Error 0.127
|
|
Change From Baseline Over Time in TmP/GFR
Week 84
|
0.39 mg/dL
Standard Error 0.136
|
|
Change From Baseline Over Time in TmP/GFR
Week 96
|
0.29 mg/dL
Standard Error 0.097
|
|
Change From Baseline Over Time in TmP/GFR
EOSII
|
0.21 mg/dL
Standard Error 0.068
|
SECONDARY outcome
Timeframe: Baseline, Week 2, Week 4, Week 12, Week 22, Week 24, Week 48, Week 60, Week 72, Week 84, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
TRP: tubular reabsorption of phosphate.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in TRP
Week 2
|
0.07 fraction of phosphorus reabsorbed
Standard Error 0.005
|
|
Change From Baseline Over Time in TRP
Week 4
|
0.03 fraction of phosphorus reabsorbed
Standard Error 0.013
|
|
Change From Baseline Over Time in TRP
Week 12
|
0.01 fraction of phosphorus reabsorbed
Standard Error 0.013
|
|
Change From Baseline Over Time in TRP
Week 22
|
0.04 fraction of phosphorus reabsorbed
Standard Error 0.007
|
|
Change From Baseline Over Time in TRP
Week 24
|
0.01 fraction of phosphorus reabsorbed
Standard Error 0.015
|
|
Change From Baseline Over Time in TRP
Week 48
|
-0.00 fraction of phosphorus reabsorbed
Standard Error 0.021
|
|
Change From Baseline Over Time in TRP
Week 60
|
0.03 fraction of phosphorus reabsorbed
Standard Error 0.016
|
|
Change From Baseline Over Time in TRP
Week 72
|
-0.02 fraction of phosphorus reabsorbed
Standard Error 0.035
|
|
Change From Baseline Over Time in TRP
Week 84
|
0.02 fraction of phosphorus reabsorbed
Standard Error 0.019
|
|
Change From Baseline Over Time in TRP
Week 96
|
0.02 fraction of phosphorus reabsorbed
Standard Error 0.014
|
|
Change From Baseline Over Time in TRP
EOSII
|
0.01 fraction of phosphorus reabsorbed
Standard Error 0.011
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
P1NP: procollagen type 1 N-propeptide.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in P1NP
Week 12
|
99.18 ng/mL
Standard Error 11.403
|
|
Change From Baseline Over Time in P1NP
Week 24
|
104.33 ng/mL
Standard Error 11.153
|
|
Change From Baseline Over Time in P1NP
Week 48
|
52.49 ng/mL
Standard Error 11.554
|
|
Change From Baseline Over Time in P1NP
Week 72
|
37.29 ng/mL
Standard Error 12.294
|
|
Change From Baseline Over Time in P1NP
Week 96
|
29.29 ng/mL
Standard Error 13.321
|
|
Change From Baseline Over Time in P1NP
EOSII
|
2.14 ng/mL
Standard Error 10.105
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline Over Time in P1NP
Week 12
|
133.08 percent change in P1NP
Standard Error 13.680
|
|
Percent Change From Baseline Over Time in P1NP
Week 24
|
137.80 percent change in P1NP
Standard Error 15.741
|
|
Percent Change From Baseline Over Time in P1NP
Week 48
|
76.86 percent change in P1NP
Standard Error 14.114
|
|
Percent Change From Baseline Over Time in P1NP
Week 72
|
50.46 percent change in P1NP
Standard Error 13.659
|
|
Percent Change From Baseline Over Time in P1NP
Week 96
|
41.36 percent change in P1NP
Standard Error 11.566
|
|
Percent Change From Baseline Over Time in P1NP
EOSII
|
26.20 percent change in P1NP
Standard Error 9.919
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug, with non-missing results at given time point.
CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in CTx
Week 96
|
76.80 pg/mL
Standard Error 57.357
|
|
Change From Baseline Over Time in CTx
EOSII
|
-41.32 pg/mL
Standard Error 83.144
|
|
Change From Baseline Over Time in CTx
Week 12
|
464.84 pg/mL
Standard Error 61.696
|
|
Change From Baseline Over Time in CTx
Week 24
|
404.13 pg/mL
Standard Error 55.948
|
|
Change From Baseline Over Time in CTx
Week 48
|
175.13 pg/mL
Standard Error 44.022
|
|
Change From Baseline Over Time in CTx
Week 72
|
143.11 pg/mL
Standard Error 92.503
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
CTx: carboxy-terminal cross-linked telopeptide of type I collagen.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=14 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline Over Time in CTx
Week 12
|
89.68 percent change in CTx
Standard Error 13.316
|
|
Percent Change From Baseline Over Time in CTx
Week 24
|
70.17 percent change in CTx
Standard Error 10.341
|
|
Percent Change From Baseline Over Time in CTx
Week 48
|
35.86 percent change in CTx
Standard Error 7.396
|
|
Percent Change From Baseline Over Time in CTx
Week 72
|
34.00 percent change in CTx
Standard Error 14.016
|
|
Percent Change From Baseline Over Time in CTx
Week 96
|
25.86 percent change in CTx
Standard Error 8.461
|
|
Percent Change From Baseline Over Time in CTx
EOSII
|
17.88 percent change in CTx
Standard Error 9.284
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
BALP: bone-specific alkaline phosphatase.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=13 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Change From Baseline Over Time in BALP
Week 12
|
10.93 μg/L
Standard Error 3.547
|
|
Change From Baseline Over Time in BALP
Week 24
|
5.82 μg/L
Standard Error 2.980
|
|
Change From Baseline Over Time in BALP
Week 48
|
4.50 μg/L
Standard Error 3.990
|
|
Change From Baseline Over Time in BALP
Week 72
|
3.13 μg/L
Standard Error 2.435
|
|
Change From Baseline Over Time in BALP
Week 96
|
1.14 μg/L
Standard Error 2.028
|
|
Change From Baseline Over Time in BALP
EOSII
|
-5.80 μg/L
Standard Error 3.396
|
SECONDARY outcome
Timeframe: Baseline, Week 12, Week 24, Week 48, Week 72, Week 96, EOSII (up to Week 141)Population: Full Analysis Set: all enrolled participants who receive at least one dose of study drug with non-missing results at given time point.
BALP: bone-specific alkaline phosphatase.
Outcome measures
| Measure |
Open-Label Burosumab Q4W
n=13 Participants
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Percent Change From Baseline Over Time in BALP
Week 12
|
52.54 percent change in BALP
Standard Error 15.999
|
|
Percent Change From Baseline Over Time in BALP
Week 24
|
31.37 percent change in BALP
Standard Error 11.808
|
|
Percent Change From Baseline Over Time in BALP
Week 48
|
24.35 percent change in BALP
Standard Error 17.630
|
|
Percent Change From Baseline Over Time in BALP
Week 72
|
15.13 percent change in BALP
Standard Error 13.431
|
|
Percent Change From Baseline Over Time in BALP
Week 96
|
6.92 percent change in BALP
Standard Error 10.387
|
|
Percent Change From Baseline Over Time in BALP
EOSII
|
-27.30 percent change in BALP
Standard Error 12.767
|
Adverse Events
Open-Label Burosumab Q4W
Serious events: 4 serious events
Other events: 14 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Open-Label Burosumab Q4W
n=14 participants at risk
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
Cardiac disorders
Atrial Fibrillation
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Obstruction Gastric
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Splenic Rupture
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Migraine
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Paraesthesia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
Other adverse events
| Measure |
Open-Label Burosumab Q4W
n=14 participants at risk
1.0 mg/kg burosumab Q4W, calculated based on baseline weight and up to a maximum dose of 90 mg.
|
|---|---|
|
General disorders
Influenza Like Illness
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Injection Site Bruising
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Injection Site Pain
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Injection Site Pruritus
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Injection Site Reaction
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Injection Site Urticaria
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Local Swelling
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Nodule
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Non-Cardiac Chest Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Oedema Peripheral
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Pain
|
35.7%
5/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Cardiac disorders
Bradycardia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Cardiac disorders
Pericarditis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Ear and labyrinth disorders
Hypoacusis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Abdominal Discomfort
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Abdominal Distension
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Abdominal Pain
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Abdominal Pain Upper
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Constipation
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Diarrhoea
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Dyspepsia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Gastrooesophageal Reflux Disease
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Gingival Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Gingival Swelling
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Irritable Bowel Syndrome
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Mouth Ulceration
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Nausea
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Oral Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Periodontal Disease
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Toothache
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Vomiting
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Gastrointestinal disorders
Vomiting Projectile
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Application Site Rash
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Asthenia
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Chest Discomfort
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Chest Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Drug Withdrawal Syndrome
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Fatigue
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Peripheral Swelling
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
General disorders
Pyrexia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Hepatobiliary disorders
Hepatic Steatosis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Immune system disorders
Drug Hypersensitivity
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Immune system disorders
Seasonal Allergy
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Bronchitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Conjunctivitis Bacterial
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Gingival Abscess
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Gingivitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Hordeolum
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Influenza
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Laryngitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Lice Infestation
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Lung Infection
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Nasopharyngitis
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Periodontitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Pharyngitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Pharyngitis Streptococcal
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Postoperative Wound Infection
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Respiratory Tract Infection Viral
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Root Canal Infection
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Sinusitis
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Tooth Abscess
|
50.0%
7/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Tooth Infection
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Upper Respiratory Tract Infection
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Urinary Tract Infection
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Infections and infestations
Vulvovaginal Mycotic Infection
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Concussion
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Contusion
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Fall
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Incision Site Pruritus
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Injection Related Reaction
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Ligament Sprain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Post Procedural Swelling
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Procedural Pain
|
50.0%
7/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Stress Fracture
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Sunburn
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Tooth Fracture
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Injury, poisoning and procedural complications
Tooth Injury
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood 25-Hydroxycholecalciferol Decreased
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Calcium Decreased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Cholesterol Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Glucose Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Parathyroid Hormone Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Pressure Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Testosterone Decreased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Blood Uric Acid Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Ejection Fraction Decreased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Eosinophil Count Increased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Ultrasound Kidney Abnormal
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Investigations
Vitamin D Decreased
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Metabolism and nutrition disorders
Vitamin D Deficiency
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
35.7%
5/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Arthritis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Back Pain
|
42.9%
6/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Bone Pain
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Fibromyalgia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Joint Instability
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Joint Swelling
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Limb Discomfort
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Muscle Atrophy
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Muscle Spasms
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Muscular Weakness
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Chest Pain
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Musculoskeletal Stiffness
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Neck Pain
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Osteoarthritis
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Pain In Extremity
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Pain In Jaw
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Spinal Pain
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Musculoskeletal and connective tissue disorders
Tendonitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Amnesia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Dizziness
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Dysaesthesia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Headache
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Hypoaesthesia
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Migraine
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Motor Dysfunction
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Nerve Compression
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Neuralgia
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Paraesthesia
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Restless Legs Syndrome
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Sciatica
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Somnolence
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Syncope
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Nervous system disorders
Tremor
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Anxiety
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Confusional State
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Depression
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Depressive Symptom
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Insomnia
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Irritability
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Psychiatric disorders
Nightmare
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Renal and urinary disorders
Glycosuria
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Renal and urinary disorders
Urinary Retention
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Reproductive system and breast disorders
Dysmenorrhoea
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Reproductive system and breast disorders
Ovarian Cyst
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Reproductive system and breast disorders
Uterine Haemorrhage
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
21.4%
3/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal Pain
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Productive Cough
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory Tract Congestion
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Congestion
|
28.6%
4/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Respiratory, thoracic and mediastinal disorders
Sinus Perforation
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Dermatitis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Eczema
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Hyperhidrosis
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Pruritus Generalised
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Rash
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Skin Irritation
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Urticaria
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Skin and subcutaneous tissue disorders
Xanthoma
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Vascular disorders
Hot Flush
|
7.1%
1/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
|
Vascular disorders
Hypertension
|
14.3%
2/14 • Week 0 to EOSII (up to Week 141). Mean (SE) duration of exposure to study drug was 716 (35.1) days
Treatment-emergent adverse events are presented.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee 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.
- Publication restrictions are in place
Restriction type: OTHER