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Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)

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ClinicalTrials.gov Identifier: NCT01163149
Recruitment Status : Completed
First Posted : July 15, 2010
Results First Posted : September 18, 2017
Last Update Posted : September 18, 2017
Sponsor:
Information provided by (Responsible Party):
Alexion Pharma GmbH

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypophosphatasia
Intervention Drug: asfotase alfa
Enrollment 19
Recruitment Details  
Pre-assignment Details  
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control
Hide Arm/Group Description

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Period Title: Primary Treatment Period
Started 7 6 6
Completed 7 6 6
Not Completed 0 0 0
Period Title: Extension Treatment Period
Started 7 6 6
Completed 5 5 4
Not Completed 2 1 2
Reason Not Completed
Withdrawal by Subject             2             0             1
Adverse Event             0             1             0
Noncompliance             0             0             1
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Total
Hide Arm/Group Description

Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects randomized to the concurrent control cohort were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug

Total of all reporting groups
Overall Number of Baseline Participants 7 6 6 19
Hide Baseline Analysis Population Description
All efficacy analyses were performed on the full analysis set (intent-to-treat population), which consisted of all randomized patients (n=19).
Age, Continuous  
Median (Full Range)
Unit of measure:  Years
Number Analyzed 7 participants 6 participants 6 participants 19 participants
45.0
(14 to 66)
55.0
(15 to 57)
21.0
(13 to 58)
53.0
(13 to 66)
Age, Customized  
Median (Full Range)
Unit of measure:  Years
Age at Onset of Symptoms Number Analyzed 7 participants 6 participants 6 participants 19 participants
2.0
(0.2 to 36)
2.0
(0 to 3)
0.88
(0.2 to 4.0)
2.0
(0 to 36)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Age Group Number Analyzed 7 participants 6 participants 6 participants 19 participants
Adolescent (12-17 years)
2
  28.6%
1
  16.7%
3
  50.0%
6
  31.6%
Adult (≥ 18 years)
5
  71.4%
5
  83.3%
3
  50.0%
13
  68.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
Female
6
  85.7%
4
  66.7%
2
  33.3%
12
  63.2%
Male
1
  14.3%
2
  33.3%
4
  66.7%
7
  36.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
7
 100.0%
6
 100.0%
6
 100.0%
19
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
7
 100.0%
6
 100.0%
5
  83.3%
18
  94.7%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
1
  16.7%
1
   5.3%
Hypophosphatasia (HPP) Phenotype  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 7 participants 6 participants 6 participants 19 participants
Infantile (<6 months)
1
  14.3%
2
  33.3%
1
  16.7%
4
  21.1%
Juvenile (≥ 6 months to < 18 years)
5
  71.4%
4
  66.7%
5
  83.3%
14
  73.7%
Adult (≥ 18 years)
1
  14.3%
0
   0.0%
0
   0.0%
1
   5.3%
1.Primary Outcome
Title Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP)
Hide Description Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma pyridoxal-5' phosphate (PLP)
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Combined Asfotase Alfa Group
Hide Arm/Group Description:
Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)
Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)
Control (no asfotase alfa) during primary treatment period (first 24 weeks)
Subjects from Cohort 1 and Cohort 2 treated with asfotase alfa during primary treatment period (first 24 weeks)
Overall Number of Participants Analyzed 7 6 6 13
Mean (Standard Deviation)
Unit of Measure: ng/mL
-254.96  (196.206) -564.27  (624.009) 3.13  (242.721) -397.72  (455.249)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Combined Asfotase Alfa Group
Comments PLP Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments If p-values were less than 0.05 and the Hodges-Lehman-Sen estimate favored asfotase alfa (eg, it had a negative sign indicating the between-group differences in change from Baseline favored treated patients), then superiority over control was claimed.
Statistical Test of Hypothesis P-Value 0.0285
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman-Sen
Estimated Value -302.05
Confidence Interval (2-Sided) 95%
-626.40 to -59.20
Estimation Comments [Not Specified]
2.Primary Outcome
Title Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi)
Hide Description Blood samples were collected to evaluate the effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi)
Time Frame Baseline, Week 24
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Combined Asfotase Alfa Group
Hide Arm/Group Description:
Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total)
Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)
Control (no asfotase alfa) during primary treatment period (first 24 weeks)
Subjects from Cohort 1 and Cohort 2 treated with asfotase alfa during primary treatment period (first 24 weeks)
Overall Number of Participants Analyzed 7 6 6 13
Mean (Standard Deviation)
Unit of Measure: uM
-2.027  (1.4381) -2.185  (1.3304) -1.052  (2.9248) -2.100  (1.3335)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Combined Asfotase Alfa Group
Comments PPi Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments If p-values were less than 0.05 and the Hodges-Lehman-Sen estimate favored asfotase alfa (eg, it had a negative sign indicating the between-group differences in change from Baseline favored treated patients), then superiority over control was claimed.
Statistical Test of Hypothesis P-Value 0.0715
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehman-Sen
Estimated Value -1.825
Confidence Interval (2-Sided) 95%
-3.210 to 0.230
Estimation Comments Estimate and exact confidence interval are from Hodges-Lehmann-Sen method for location shift in distribution between the treatment group and the control group.
3.Primary Outcome
Title Safety and Tolerability of Asfotase Alfa
Hide Description The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa was assessed by routine monitoring of patients for treatment-emergent adverse events (TEAEs) and injection-associated reactions (IARs).
Time Frame Up to 288 weeks exposure to asfotase alfa
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Safety Set. Control group and asfotase alfa Cohorts during the primary treatment period (first 24 weeks of study); all patients with asfotase alfa exposure during open-label extension treatment period.
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Cumulative Exposure to Asfotase Alfa
Hide Arm/Group Description:
Primary Treatment Period (first 24 week). Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total).
Primary Treatment Period (first 24 weeks). Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total).
No asfotase alfa during primary treatment period: (first 24 weeks).
All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.
Overall Number of Participants Analyzed 7 6 6 19
Measure Type: Number
Unit of Measure: Number of Treatment-Emergent Events
Any TEAE 243 81 45 1145
Not related TEAEs 110 69 45 731
Related TEAEs 133 12 0 414
Injection site reactions 133 12 0 385
Serious TEAEs 1 1 4 29
TEAEs leading to withdrawal 0 0 0 2
Deaths 0 0 0 0
4.Secondary Outcome
Title Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA)
Hide Description A DXA scan was performed to evaluate bone mineral content (BMC) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks).
Time Frame Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.
Overall Number of Participants Analyzed 7 6 6 19
Mean (Standard Deviation)
Unit of Measure: g
Hip total BMC Week 24 Number Analyzed 4 participants 5 participants 4 participants 9 participants
-3.288  (7.7669) 1.214  (2.2154) 1.288  (0.9161) -0.787  (5.5411)
Hip total BMC Week 48 Number Analyzed 1 participants 1 participants 4 participants 6 participants
1.160 [1]   (NA) 4.530 [1]   (NA) 2.320  (1.3990) 2.495  (1.5438)
Hip total BMC Week 96 Number Analyzed 4 participants 4 participants 3 participants 11 participants
0.082  (1.4046) 4.345  (4.0466) 2.907  (2.0087) 2.403  (3.1702)
Hip total BMC Week 144 Number Analyzed 3 participants 4 participants 3 participants 10 participants
1.630  (1.8719) 5.043  (5.5955) 4.533  (1.4621) 3.866  (3.7577)
Hip total BMC Week 192 Number Analyzed 2 participants 4 participants 3 participants 9 participants
1.080  (2.0082) 4.725  (6.4843) 2.910  (0.2910) 3.310  (4.3124)
Hip total BMC Week 240 Number Analyzed 2 participants 3 participants 3 participants 8 participants
0.550  (2.4042) 6.807  (5.7557) -0.673  (0.1644) 2.438  (4.8626)
Hip Total BMC Week 288 Number Analyzed 0 participants 1 participants 0 participants 1 participants
-2.780 [1]   (NA) -2.780 [1]   (NA)
Hip Total BMC Last Overall Exposure Number Analyzed 4 participants 5 participants 4 participants 13 participants
0.080  (1.8713) 3.604  (5.8284) 0.328  (2.0062) 1.512  (4.0224)
Lumbar Spine BMC Week 24 Number Analyzed 7 participants 5 participants 5 participants 12 participants
2.477  (2.5616) 2.768  (2.0007) 1.432  (1.7824) 2.598  (2.2488)
Lumbar Spine BMC Week 48 Number Analyzed 1 participants 1 participants 5 participants 7 participants
2.420 [1]   (NA) 5.550 [1]   (NA) 4.842  (5.7882) 4.597  (4.8298)
Lumbar Spine BMC Week 96 Number Analyzed 7 participants 5 participants 4 participants 16 participants
3.356  (4.4566) 4.174  (3.7068) 7.330  (5.6953) 4.605  (4.5680)
Lumbar Spine BMC Week 144 Number Analyzed 5 participants 5 participants 4 participants 14 participants
2.086  (5.2198) 5.828  (3.9791) 6.710  (4.0174) 4.744  (4.6193)
Lumbar Spine BMC Week 192 Number Analyzed 5 participants 5 participants 4 participants 14 participants
2.094  (16.4419) 6.162  (4.1628) 5.197  (5.7568) 4.434  (9.9797)
Lumbar Spine BMC Week 240 Number Analyzed 5 participants 4 participants 4 participants 13 participants
3.536  (17.0957) 3.298  (2.4931) 5.037  (4.7161) 3.925  (10.2539)
Lumbar Spine BMC Week 288 Number Analyzed 1 participants 1 participants 0 participants 2 participants
20.190 [1]   (NA) 6.500 [1]   (NA) 13.705  (10.1894)
Lumbar Spine BMC Last Overall Exposure Number Analyzed 7 participants 5 participants 5 participants 17 participants
4.306  (14.5714) 5.130  (3.5930) 6.714  (5.1113) 5.256  (9.5103)
Whole Body BMC Week 24 Number Analyzed 7 participants 5 participants 5 participants 12 participants
-21.871  (35.4370) 41.454  (20.0358) 237.248  (414.0877) 4.514  (43.5228)
Whole Body BMC Week 48 Number Analyzed 1 participants 1 participants 5 participants 7 participants
49.820 [1]   (NA) 72.530 [1]   (NA) 30.228  (82.4369) 39.070  (69.2934)
Whole Body BMC Week 96 Number Analyzed 7 participants 5 participants 4 participants 16 participants
7.537  (74.2838) 59.604  (97.9214) 98.018  (111.9259) 46.428  (93.5046)
Whole Body BMC Week 144 Number Analyzed 5 participants 5 participants 4 participants 14 participants
-48.236  (111.6604) 17.446  (173.3574) 92.063  (107.9837) 15.307  (138.3534)
Whole Body BMC Week 192 Number Analyzed 5 participants 5 participants 4 participants 14 participants
-121.916  (92.0001) 23.938  (195.8402) 50.375  (99.6281) -20.599  (151.5153)
Whole Body BMC Week 240 Number Analyzed 5 participants 4 participants 4 participants 13 participants
-97.706  (106.6581) 82.310  (223.0794) 40.572  (162.1575) 0.231  (172.0218)
Whole Body BMC Week 288 Number Analyzed 1 participants 1 participants 0 participants 2 participants
-243.080 [1]   (NA) -144.660 [1]   (NA) -193.870  (69.5934)
Whole Body BMC Last Overall Exposure Number Analyzed 7 participants 5 participants 5 participants 17 participants
-113.296  (178.8050) 11.252  (217.5674) 82.548  (128.7017) -19.063  (188.0498)
[1]
Data available for only 1 subject
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Hip Total BMC Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3301
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value -0.910
Confidence Interval (2-Sided) 95%
-3.320 to 1.780
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Lumbar Spine BMC Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.3827
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value 1.330
Confidence Interval (2-Sided) 95%
-1.360 to 3.120
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Whole Body BMC Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0485
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value -77.100
Confidence Interval (2-Sided) 95%
-917.440 to -1.740
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA)
Hide Description A DXA scan was performed to evaluate bone bone mineral density (BMD) of the spine, hip, and whole body during the primary (first 24 weeks) and extension treatment periods (up to 288 weeks).
Time Frame Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288.
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa: Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (total of 2.1 mg/kg/week) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa: Cohort 2: Daily SC injections of 0.5 mg/kg Asfotase Alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

All subjects from Cohort 1, Cohort 2, or Control group with any asfotase alfa exposure. During primary treatment period, N=13. During open-label extension treatment period, N=19.
Overall Number of Participants Analyzed 7 6 6 19
Mean (Standard Deviation)
Unit of Measure: g/cm2
Hip total BMD Week 24 Number Analyzed 4 participants 5 participants 4 participants 9 participants
0.0477  (0.07710) 0.0094  (0.02441) 0.0195  (0.01642) 0.0251  (0.05361)
Hip total BMD Week 48 Number Analyzed 1 participants 1 participants 4 participants 6 participants
0.0190 [1]   (NA) 0.0240 [1]   (NA) 0.0590  (0.04109) 0.0465  (0.03729)
Hip total BMD Week 96 Number Analyzed 4 participants 4 participants 3 participants 11 participants
0.0003  (0.00532) 0.0780  (0.06703) 0.0480  (0.04943) 0.0415  (0.05542)
Hip total BMD Week 144 Number Analyzed 3 participants 4 participants 3 participants 10 participants
0.0340  (0.02524) 0.0923  (0.07682) 0.0933  (0.04150) 0.0751  (0.05741)
Hip total BMD Week 192 Number Analyzed 2 participants 4 participants 3 participants 9 participants
0.0135  (0.00919) 0.0983  (0.10856) 0.0563  (0.07100) 0.0654  (0.08327)
Hip total BMD Week 240 Number Analyzed 2 participants 3 participants 3 participants 8 participants
0.0115  (0.02192) 0.1137  (0.05701) -0.0073  (0.06178) 0.0428  (0.07481)
Hip total BMD Week 288 Number Analyzed 0 participants 1 participants 0 participants 1 participants
-0.0200 [1]   (NA) -0.0200 [1]   (NA)
Hip total BMD Last Overall Exposure Number Analyzed 4 participants 5 participants 4 participants 13 participants
-0.0115  (0.03899) 0.0658  (0.07776) 0.0207  (0.07549) 0.0282  (0.07038)
Lumbar Spine BMD Week 24 Number Analyzed 7 participants 5 participants 5 participants 12 participants
0.0269  (0.02113) 0.0272  (0.01492) 0.0098  (0.02475) 0.0270  (0.01802)
Lumbar Spine BMD Week 48 Number Analyzed 1 participants 1 participants 5 participants 7 participants
0.0480 [1]   (NA) 0.0590 [1]   (NA) 0.0914  (0.05647) 0.0806  (0.04978)
Lumbar Spine BMD Week 96 Number Analyzed 7 participants 5 participants 4 participants 16 participants
0.0414  (0.05230) 0.0554  (0.04271) 0.1158  (0.08060) 0.0644  (0.06210)
Lumbar Spine BMD Week 144 Number Analyzed 5 participants 5 participants 4 participants 14 participants
0.0200  (0.06257) 0.0850  (0.05323) 0.1138  (0.05734) 0.0700  (0.06688)
Lumbar Spine BMD Week 192 Number Analyzed 5 participants 5 participants 4 participants 14 participants
0.0554  (0.13220) 0.0766  (0.04180) 0.1123  (0.05197) 0.0792  (0.08423)
Lumbar Spine BMD Week 240 Number Analyzed 5 participants 4 participants 4 participants 13 participants
0.0750  (0.14168) 0.0455  (0.04107) 0.1027  (0.04786) 0.0745  (0.09073)
Lumbar Spine BMD Week 288 Number Analyzed 1 participants 1 participants 0 participants 2 participants
0.1860 [1]   (NA) 0.0700 [1]   (NA) 0.1280  (0.08202)
Lumbar Spine BMD Last Overall Exposure Number Analyzed 7 participants 5 participants 5 participants 17 participants
0.0737  (0.11346) 0.0492  (0.04649) 0.1194  (0.04999) 0.0799  (0.08241)
Whole Body BMD Week 24 Number Analyzed 7 participants 5 participants 5 participants 12 participants
-0.0003  (0.01788) -0.0122  (0.01055) 0.0206  (0.03173) -0.0052  (0.01589)
Whole Body BMD Week 48 Number Analyzed 1 participants 1 participants 5 participants 7 participants
0.0050 [1]   (NA) 0.0090 [1]   (NA) 0.0178  (0.05277) 0.0147  (0.04342)
Whole Body BMD Week 96 Number Analyzed 7 participants 5 participants 4 participants 16 participants
-0.0103  (0.03523) -0.0100  (0.04136) 0.0230  (0.04872) -0.0019  (0.04059)
Whole Body BMD Week 144 Number Analyzed 5 participants 5 participants 4 participants 14 participants
-0.0250  (0.03662) -0.0278  (0.05823) -0.0060  (0.04721) -0.0206  (0.04542)
Whole Body BMD Week 192 Number Analyzed 5 participants 5 participants 4 participants 14 participants
-0.0532  (0.02477) -0.0220  (0.07088) -0.0212  (0.06209) -0.0329  (0.05358)
Whole Body BMD Week 240 Number Analyzed 5 participants 4 participants 4 participants 13 participants
-0.0426  (0.05601) -0.0122  (0.08610) -0.0493  (0.06965) -0.0353  (0.06615)
Whole Body BMD Week 288 Number Analyzed 1 participants 1 participants 0 participants 2 participants
-0.1140 [1]   (NA) -0.0710 [1]   (NA) -0.0925  (0.03041)
Whole Body BMD Last Overall Exposure Number Analyzed 7 participants 5 participants 5 participants 17 participants
-0.0501  (0.07360) -0.0298  (0.08785) -0.0224  (0.05773) -0.0360  (0.07036)
[1]
Data available for only 1 subject
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Hip Total Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7357
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value -0.0125
Confidence Interval (2-Sided) 95%
-0.0400 to 0.0390
Estimation Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Lumbar Spine BMD Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2439
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value 0.0255
Confidence Interval (2-Sided) 95%
-0.0090 to 0.0410
Estimation Comments [Not Specified]
Show Statistical Analysis 3 Hide Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Whole Body BMD Change from Baseline to Week 24
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1222
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value -0.0315
Confidence Interval (2-Sided) 95%
-0.0590 to 0.0120
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT)
Hide Description The patient was instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement was distance walked (in meters).
Time Frame Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients). Among the 6 control subjects, only 4 had both a Baseline and Week 24 value.
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects From Cohort 1 and Cohort 2 treated with asfotase alfa (N=13) during Primary Treatment Period, and all subjects exposed to asfotase alfa (N=19) during extension treatment period.
Overall Number of Participants Analyzed 7 6 6 19
Mean (Standard Deviation)
Unit of Measure: meters
Change from Baseline to Week 24 Number Analyzed 7 participants 6 participants 4 participants 13 participants
64.7  (73.04) 43.5  (43.18) 13.5  (69.77) 54.9  (59.71)
Change from Baseline Last Overall Exposure Number Analyzed 7 participants 6 participants 5 participants 18 participants
89.4  (81.32) 2.2  (121.79) 74.4  (107.40) 56.2  (104.85)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Concurrent Control, Asfotase Alfa Combined
Comments Week 24 Change from Baseline
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.1303
Comments Two-sided with p-value threshold <0.05 for statistical significance
Method Wilcoxon rank-sum
Comments [Not Specified]
Method of Estimation Estimation Parameter Hodges-Lehmann-Sen
Estimated Value 44.0
Confidence Interval (2-Sided) 95%
-73.0 to 114.0
Estimation Comments Estimate and exact confidence interval are from Hodges-Lehmann-Sen method for location shift in distribution between the treatment group and the control group
7.Secondary Outcome
Title Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume
Hide Description A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Volume/Bone Volume (%). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time Frame Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.
Overall Number of Participants Analyzed 6 6 6 12
Mean (Standard Deviation)
Unit of Measure: percentage of volume
1.213  (3.2488) -2.845  (2.3769) 0.200  (4.7679) -0.816  (3.4434)
8.Secondary Outcome
Title Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness
Hide Description A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Osteoid Thickness (um). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time Frame Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.
Overall Number of Participants Analyzed 6 6 6 12
Mean (Standard Deviation)
Unit of Measure: um
-0.013  (3.6333) -1.516  (2.3556) -1.132  (6.0884) -0.764  (3.0229)
9.Secondary Outcome
Title Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time
Hide Description A trans-iliac crest bone biopsy was performed to quantify changes from Baseline in histomorphometric parameters relevant for evaluation of osteomalacia severity, including Mineralization Lag Time (days). The difference in time under observation between asfotase alfa groups (Week 48) and control group (Week 24) resulted from study design, ie, control subjects transitioned to active treatment after the Week 24 visit.
Time Frame Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups).
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Full analysis set (intent-to-treat, all randomized patients)
Arm/Group Title 0.3 mg/kg Asfotase Alfa 0.5 mg/kg Asfotase Alfa Concurrent Control Asfotase Alfa Combined
Hide Arm/Group Description:

Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total) during Primary Treatment Period through Week 24.

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

No asfotase alfa during first 24 weeks (primary treatment period).

Following completion of the Week 24 visit, all subjects were eligible to participate in an open-label extension treatment period. In this extension period, all subjects were treated with daily SC injections of 0.5 mg/kg/day asfotase alfa (a total of 3.5 mg/kg/week) for approximately 24 weeks, then subjects received 1 mg/kg/day 6 days/week until regulatory approval of the drug.

Subjects from primary treatment period asfotase alfa groups.
Overall Number of Participants Analyzed 4 5 5 9
Mean (Standard Deviation)
Unit of Measure: days
-908.255  (1313.6158) -126.946  (142.2929) 78.296  (167.0895) -474.195  (909.2779)
Time Frame up to 288 weeks
Adverse Event Reporting Description Only adverse events with an onset date are included in the cumulative exposure category.
 
Arm/Group Title 0.3 mg/kg Asfotase Alfa (First 24 Weeks) 0.5 mg/kg Asfotase Alfa (First 24 Weeks) Concurrent Control (First 24 Weeks) Cumulative Exposure to Asfotase Alfa
Hide Arm/Group Description Asfotase alfa Cohort 1: Daily SC injections of 0.3 mg/kg asfotase alfa (2.1 mg/kg/week total) Asfotase alfa Cohort 2: Daily SC injections of 0.5 mg/kg asfotase alfa (3.5 mg/kg/week total)

No asfotase alfa treatment during primary treatment period: first 24 weeks.

After 24 weeks, Control Group subjects were eligible to begin asfotase alfa treatment in the open-label extension treatment period.

Adverse events occurring in subjects from Cohort 1, Cohort 2 and original Control group during exposure to asfotase alfa.
All-Cause Mortality
0.3 mg/kg Asfotase Alfa (First 24 Weeks) 0.5 mg/kg Asfotase Alfa (First 24 Weeks) Concurrent Control (First 24 Weeks) Cumulative Exposure to Asfotase Alfa
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/7 (0.00%)      0/6 (0.00%)      0/6 (0.00%)      0/19 (0.00%)    
Show Serious Adverse Events Hide Serious Adverse Events
0.3 mg/kg Asfotase Alfa (First 24 Weeks) 0.5 mg/kg Asfotase Alfa (First 24 Weeks) Concurrent Control (First 24 Weeks) Cumulative Exposure to Asfotase Alfa
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1/7 (14.29%)      1/6 (16.67%)      2/6 (33.33%)      9/19 (47.37%)    
Congenital, familial and genetic disorders         
Arnold-Chiari Malformation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ear and labyrinth disorders         
Tympanic Membrane Perforation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders         
Colitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Hypoaesthesia Oral  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
General disorders         
Chills  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  3
Device Dislocation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Hypersensitivity  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Immune system disorders         
Anaphylactoid Reaction  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations         
Abscess  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Cellulitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Endocarditis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Enterovirus Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Staphylococcal Abscess  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Staphylococcal Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/19 (5.26%)  1
Gastroenteritis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Injury, poisoning and procedural complications         
Femur Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Humerus Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Musculoskeletal and connective tissue disorders         
Pain in Extremity  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Back Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Muscular Weakness  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Osteoarthritis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Adrenal Adenoma  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Nervous system disorders         
Convulsion  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  3
Headache  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Intracranial Pressure Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA 13.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
0.3 mg/kg Asfotase Alfa (First 24 Weeks) 0.5 mg/kg Asfotase Alfa (First 24 Weeks) Concurrent Control (First 24 Weeks) Cumulative Exposure to Asfotase Alfa
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   7/7 (100.00%)      6/6 (100.00%)      6/6 (100.00%)      19/19 (100.00%)    
Blood and lymphatic system disorders         
Anaemia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Cardiac disorders         
Atrial Fibrillation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ear and labyrinth disorders         
Ear Discomfort  1  1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 2/19 (10.53%)  2
Ear Pruritis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Cerumen Impaction  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Ear Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Tinnitus  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Tympanic Membrane Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Tympanic Membrane Perforation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Vertigo  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Endocrine disorders         
Goitre  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Hypothyroidism  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Eye disorders         
Conjunctivitis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Lacrimation Increased  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Blepharitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Conjunctival Deposit  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/19 (10.53%)  2
Keratopathy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Deposit Eye  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 7/19 (36.84%)  8
Vitreous Detachment  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  3
Optic Atrophy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Cataract  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Conjunctival Discolouration  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Conjunctival Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Corneal Deposits  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dry Eye  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Eye Irritation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Eyelid Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Photopsia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Punctate Keratitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal disorders         
Nausea  1  1/7 (14.29%)  2 1/6 (16.67%)  1 1/6 (16.67%)  2 4/19 (21.05%)  7
Constipation  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  4
Diarrhoea  1  0/7 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 2/19 (10.53%)  3
Hyperchlorhydria  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Irritable Bowel Syndrome  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Vomiting  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Tooth Loss  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 3/19 (15.79%)  3
Dyspepsia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  3
Abdominal Pain Upper  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  6
Gastroesophageal Reflux Disease  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Loose Tooth  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Abdominal Discomfort  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Abdominal Hernia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Abdominal Mass  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Colitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Colonic Polyp  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dental Caries  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dysphagia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal Haemorrhage  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal Motility Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gingival Hypertrophy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gingival Swelling  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gingivitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Tooth Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
General disorders         
Injection Site Erythema  1  3/7 (42.86%)  61 2/6 (33.33%)  5 0/6 (0.00%)  0 13/19 (68.42%)  121
Injection Site Haematoma  1  3/7 (42.86%)  14 1/6 (16.67%)  6 0/6 (0.00%)  0 10/19 (52.63%)  33
Injection Site Pain  1  4/7 (57.14%)  20 0/6 (0.00%)  0 0/6 (0.00%)  0 6/19 (31.58%)  26
Fatigue  1  0/7 (0.00%)  0 3/6 (50.00%)  5 0/6 (0.00%)  0 4/19 (21.05%)  7
Injection Site Pruritis  1  3/7 (42.86%)  16 0/6 (0.00%)  0 0/6 (0.00%)  0 5/19 (26.32%)  20
Injection Site Discoloration  1  2/7 (28.57%)  9 0/6 (0.00%)  0 0/6 (0.00%)  0 9/19 (47.37%)  66
Injection Site Swelling  1  2/7 (28.57%)  10 0/6 (0.00%)  0 0/6 (0.00%)  0 4/19 (21.05%)  12
Oedema Peripheral  1  1/7 (14.29%)  7 1/6 (16.67%)  1 0/6 (0.00%)  0 8/19 (42.11%)  16
Asthenia  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Facial Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Feeling Abnormal  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Induration  1  1/7 (14.29%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  4
Injection Site Papule  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Local Swelling  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Medical Device Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Pain  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 3/19 (15.79%)  4
Pyrexia  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Atrophy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 5/19 (26.32%)  8
Injection Site Mass  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  5
Injection Site Reaction  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 7/19 (36.84%)  56
Injection Site Warmth  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  3
Gait Disturbance  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Injection Site Hypertrophy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/19 (21.05%)  12
Axillary Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Catherter Site Erythema  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Catheter SIte Inflammation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  17
Cyst  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Device Failure  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Fibrosis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Injection Site Exfoliation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Haemorrhage  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Inflammation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Macule  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  10
Injection Site Nodule  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Injection Site Scar  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injection Site Vesicles  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Malaise  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Hepatobiliary disorders         
Hepatic Steatosis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Immune system disorders         
Food Allergy  1  1/7 (14.29%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Seasonal Allergy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Immunisation Reaction  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Infections and infestations         
Nasopharyngitis  1  0/7 (0.00%)  0 2/6 (33.33%)  2 2/6 (33.33%)  2 6/19 (31.58%)  8
Sinusitis  1  2/7 (28.57%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 5/19 (26.32%)  20
Upper Respiratory Tract Infection  1  1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 7/19 (36.84%)  22
Diverticulitis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastroenteritis Viral  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Rhinitis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Tinea Pedis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Tooth Infection  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/19 (10.53%)  5
Viral Infection  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastroenteritis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 2/19 (10.53%)  3
Lower Respiratory Tract Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Pharyngitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Staphylococcal Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Influenza  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Abscess  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Acute Sinusitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Adenovirus Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Bronchiolitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Cellulitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Conjunctivitis Bacterial  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Diarrhoea Infectious  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ear Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Endocarditis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gastrointestinal Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Herpes Zoster  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Oral Candidiasis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Otitis Media  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Paronychia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Post Procedural Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Respiratory Tract Infection Viral  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Staphylococcal Abscess  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Staphylococcal Skin Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Tinea Cruris  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Tinea Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Urinary Tract Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Vaginitis Bacterial  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Viral Pharyngitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Viral Upper Respiratory Tract Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Vulvovaginal Mycotic Infection  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Injury, poisoning and procedural complications         
Fall  1  1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 5/19 (26.32%)  8
Contusion  1  0/7 (0.00%)  0 1/6 (16.67%)  1 1/6 (16.67%)  1 3/19 (15.79%)  4
Foot Fracture  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 7/19 (36.84%)  10
Joint Sprain  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 3/19 (15.79%)  3
Post Procedural Swelling  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/19 (10.53%)  2
Post-Traumatic Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 4/19 (21.05%)  4
Fibula Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Procedural Pain  1  0/7 (0.00%)  0 1/6 (16.67%)  2 1/6 (16.67%)  3 5/19 (26.32%)  11
Joint Dislocation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/19 (5.26%)  1
Ankle Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Arthropod Bite  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  4
Tibia Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  3
Tooth Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Excoriation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Femur Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Hand Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ilium Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Joint Injury  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  3
Limb Injury  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Meniscus Lesion  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Procedural Nausea  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Procedural Vomiting  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Radius Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Thoracic Vertebral Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ulna Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Upper Limb Fracture  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Wound  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Investigations         
Blood human Chorionic Gonadotropin Abnormal  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Blood Parathyroid Hormone Increased  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 2/19 (10.53%)  3
Blood Pressure Increased  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Heart Rate Increased  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Weight Increased  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  3
Vitamin D Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Alanine Aminotransferase Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Aspartate Aminotransferase Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  3
Blood 25-Hydroxycholecalciferol Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Blood Alkaline Phoshatase Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Gamma-Glutamyltransferase Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Haemaglobin Decreased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Heart Rate Decreased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Lymphocyte Count Decreased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Neutrophil Count Decreased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Physical Examination Abnormal  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Red Blood Cells Urine  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ultrasound Kidney Abnormal  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
White Blood Cell Count Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Metabolism and nutrition disorders         
Gout  1  1/7 (14.29%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  7
Musculoskeletal and connective tissue disorders         
Back Pain  1  2/7 (28.57%)  3 3/6 (50.00%)  3 1/6 (16.67%)  3 10/19 (52.63%)  14
Joint Swelling  1  2/7 (28.57%)  7 3/6 (50.00%)  3 0/6 (0.00%)  0 7/19 (36.84%)  16
Pain In Extremity  1  2/7 (28.57%)  13 3/6 (50.00%)  7 1/6 (16.67%)  1 12/19 (63.16%)  46
Arthralgia  1  2/7 (28.57%)  6 2/6 (33.33%)  3 1/6 (16.67%)  2 13/19 (68.42%)  41
Bone Pain  1  1/7 (14.29%)  3 2/6 (33.33%)  2 0/6 (0.00%)  0 9/19 (47.37%)  14
Neck Pain  1  2/7 (28.57%)  2 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  5
Arthritis  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Arthropathy  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Musculoskeletal Chest Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 1/6 (16.67%)  4 2/19 (10.53%)  2
Musculoskeletal Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 8/19 (42.11%)  11
Musculoskeletal Stiffness  1  1/7 (14.29%)  2 0/6 (0.00%)  0 1/6 (16.67%)  3 2/19 (10.53%)  3
Myalgia  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 3/19 (15.79%)  4
Nodule On Extremity  1  0/7 (0.00%)  0 1/6 (16.67%)  4 0/6 (0.00%)  0 2/19 (10.53%)  5
Deformity Thorax  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Jaw Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Muscle Spasms  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 3/19 (15.79%)  4
Tendon Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  2 0/19 (0.00%)  0
Tendon Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 0/19 (0.00%)  0
Tendonitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 3/19 (15.79%)  3
Osteoarthritis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 4/19 (21.05%)  4
Bursitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  3
Metatarsalgia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  7
Chondrocalcinosis Pyrophosphate  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Joint Range of Motion Decreased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  3
Flank Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Joint Stiffness  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Joint Warmth  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Lower Extremity Mass  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Muscular Weakness  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Musculoskeletal Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Sacroiliitis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Spinal Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Trigger Finger  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Wrist Deformity  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Melanocytic Naevus  1  1/7 (14.29%)  6 0/6 (0.00%)  0 0/6 (0.00%)  0 0/19 (0.00%)  0
Benign Renal Neoplasm  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Lipoma  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  2
Lung Neoplasm  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Uterine Leiomyoma  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Nervous system disorders         
Headache  1  2/7 (28.57%)  4 1/6 (16.67%)  1 1/6 (16.67%)  1 5/19 (26.32%)  28
Dizziness  1  1/7 (14.29%)  1 1/6 (16.67%)  1 0/6 (0.00%)  0 7/19 (36.84%)  7
Dizziness Exertional  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dysgeusia  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Hypoaesthesia  1  0/7 (0.00%)  0 1/6 (16.67%)  2 0/6 (0.00%)  0 3/19 (15.79%)  5
Loss of Consciousness  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Paraesthesia  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 4/19 (21.05%)  9
Post-Traumatic Headache  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Migraine  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  5
Balance Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Burning Sensation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Intracranial Pressure Increased  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Neuralgia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Neuropathy Peripheral  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Sinus Headache  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Psychiatric disorders         
Insomnia  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Nightmare  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Initial Insomnia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Anxiety  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Depression  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Intentional Self-Injury  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Sleep Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Renal and urinary disorders         
Nephrolithiasis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  3
Nephrocalcinosis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Bladder Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Haematuria  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  3
Renal Cyst  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Renal Pain  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Reproductive system and breast disorders         
Dysmenorrhea  1  2/7 (28.57%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  8
Pelvic Pain  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Vaginal Haemorrhage  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Breast Calcifications  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Breast Mass  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Ovarian Cyst  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Spermatocele  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Respiratory, thoracic and mediastinal disorders         
Oropharyngeal Pain  1  2/7 (28.57%)  2 2/6 (33.33%)  2 0/6 (0.00%)  0 4/19 (21.05%)  5
Cough  1  2/7 (28.57%)  3 0/6 (0.00%)  0 0/6 (0.00%)  0 5/19 (26.32%)  6
Nasal Congestion  1  1/7 (14.29%)  1 0/6 (0.00%)  0 1/6 (16.67%)  1 2/19 (10.53%)  2
Respiratory Tract Congestion  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Sinus Congestion  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Respiratory Disorder  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/19 (5.26%)  1
Rhinorrhoea  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Aspiration  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Bronchial Hypereactivity  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dry Throat  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Emphysema  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Hypoxia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Sleep Apnoea Syndrome  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Skin and subcutaneous tissue disorders         
Dermal Cyst  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Erythema  1  1/7 (14.29%)  8 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  8
Ingrowing Nail  1  0/7 (0.00%)  0 1/6 (16.67%)  3 0/6 (0.00%)  0 1/19 (5.26%)  3
Onychomadesis  1  0/7 (0.00%)  0 1/6 (16.67%)  1 0/6 (0.00%)  0 1/19 (5.26%)  1
Rash Macular  1  1/7 (14.29%)  1 0/6 (0.00%)  0 0/6 (0.00%)  0 3/19 (15.79%)  4
Scar  1  0/7 (0.00%)  0 0/6 (0.00%)  0 1/6 (16.67%)  1 1/19 (5.26%)  1
Skin Lesion  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 2/19 (10.53%)  2
Acne  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Actinic Keratosis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Blister  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dermatitis Contact  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Dermatitis Diaper  1  1/7 (14.29%)  1 1/6 (16.67%)  1 1/6 (16.67%)  1 1/19 (5.26%)  2
Dry Skin  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Excessive Skin  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Ingrown Hair  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Onychalgia  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Photodermatosis  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Rash  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Rash Papular  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Skin Discolouration  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Skin Hyperpigmentation  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Surgical and medical procedures         
Colon Polypectomy  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
Vascular disorders         
Hypertension  1  0/7 (0.00%)  0 0/6 (0.00%)  0 0/6 (0.00%)  0 1/19 (5.26%)  1
1
Term from vocabulary, MedDRA 13.0
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.
Results Point of Contact
Name/Title: Director of Clinical Trials
Organization: Alexion Pharmaceuticals, Inc.
Phone: 475-230-2596
Responsible Party: Alexion Pharma GmbH
ClinicalTrials.gov Identifier: NCT01163149     History of Changes
Other Study ID Numbers: ENB-009-10
First Submitted: June 24, 2010
First Posted: July 15, 2010
Results First Submitted: June 27, 2017
Results First Posted: September 18, 2017
Last Update Posted: September 18, 2017