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Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)

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ClinicalTrials.gov Identifier: NCT01176266
Recruitment Status : Completed
First Posted : August 5, 2010
Results First Posted : February 26, 2018
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Study Type Interventional
Study Design Allocation: N/A;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Hypophosphatasia
Intervention Drug: asfotase alfa
Enrollment 69
Recruitment Details The main criteria for inclusion in the study were male and female patients less than or equal to 5 years of age with a documented diagnosis of infantile onset hypophosphatasia (HPP) who were otherwise medically stable. Patients must have had onset of HPP signs/symptoms prior to 6 months of age.
Pre-assignment Details  
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Period Title: Overall Study
Started 69
Completed 60
Not Completed 9
Reason Not Completed
Death             6
Withdrawal by Subject             3
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Baseline Participants 69
Hide Baseline Analysis Population Description
Full Analysis Set (defined as all patients who received any asfotase alfa treatment)
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Weeks
Number Analyzed 69 participants
113.42  (108.912)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants
Female
36
  52.2%
Male
33
  47.8%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants
Hispanic or Latino
1
   1.4%
Not Hispanic or Latino
63
  91.3%
Unknown or Not Reported
5
   7.2%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 69 participants
American Indian or Alaskan Native
0
   0.0%
Asian
7
  10.1%
Black or African American
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
White
54
  78.3%
Other
3
   4.3%
Unknown
5
   7.2%
1.Primary Outcome
Title Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
Hide Description The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at Week 24 were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets).
Time Frame From Baseline to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 69
Median (Full Range)
Unit of Measure: scores on a scale
2.00
(-1.67 to 3.00)
2.Primary Outcome
Title Safety and Tolerability of Repeated Subcutaneous (SC) Injections of Asfotase Alfa
Hide Description Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients was assessed by the number of patients with 1 or more treatment-emergent adverse event.
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 69
Measure Type: Count of Participants
Unit of Measure: Participants
69
 100.0%
3.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Skeletal Manifestations of Hypophosphatasia (HPP)
Hide Description The effect of asfotase alfa treatment on skeletal manifestations of HPP (i.e., change in rickets severity) was measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment. The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets).
Time Frame Up to 72 Months or regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 67
Median (Full Range)
Unit of Measure: scores on a scale
2.33
(-2.67 to 3.00)
4.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Ventilator-free Survival (Week 312)
Hide Description For patients who were not on respiratory support at the time of enrollment, the Kaplan-Meier estimate of ventilator-free survival at the end of the study
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Patients on respiratory support at Baseline were excluded from the analysis.
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 45
Measure Type: Number
Unit of Measure: Probability
0.81
5.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Respiratory Function
Hide Description Effect of asfotase alfa treatment on respiratory function as measured by the shift in proportion of patients requiring respiratory support at their last assessment compared with Baseline.
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Baseline Asfotase Alfa - Without Respiratory Support at Baseline Asfotase Alfa - With Respiratory Support at Baseline
Hide Arm/Group Description:
Baseline assessment before initiation of asfotase alfa
Results at End of Study for Those Without Respiratory Support at Baseline (Last Assessment for Each Patient)
Results at End of Study for Those With Respiratory Support at Baseline (Last Assessment for Each Patient)
Overall Number of Participants Analyzed 69 45 24
Measure Type: Count of Participants
Unit of Measure: Participants
No respiratory support
45
  65.2%
43
  95.6%
11
  45.8%
Supplemental oxygen
6
   8.7%
1
   2.2%
2
   8.3%
Biphasic positive airway pressure
0
   0.0%
0
   0.0%
0
   0.0%
Continuous positive airway pressure
4
   5.8%
1
   2.2%
2
   8.3%
Mechanical ventilation
13
  18.8%
0
   0.0%
9
  37.5%
Other
1
   1.4%
0
   0.0%
0
   0.0%
6.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Physical Growth - Length/Height Z-scores Change From Baseline to Last Obtained Value
Hide Description Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in length/height Z-scores
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 66
Median (Full Range)
Unit of Measure: Z-score
0.5
(-4 to 4)
7.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Physical Growth - Weight Z-scores Change From Baseline to Last Obtained Value
Hide Description Effect of asfotase alfa treatment on physical growth as measured by change from Baseline to last assessment for each patient in weight Z-scores
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 67
Median (Full Range)
Unit of Measure: Z-score
1.0
(-5 to 6)
8.Secondary Outcome
Title Effect of Asfotase Alfa on Biomarkers - Plasma Inorganic Pyrophosphate (PPi) Change From Baseline to Last Obtained Value
Hide Description Effect of asfotase alfa on PPi as measured by change from Baseline to last assessment for each patient
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 63
Median (Full Range)
Unit of Measure: uM
-2.460
(-12.18 to 22.47)
9.Secondary Outcome
Title Effect of Asfotase Alfa on Biomarkers - Plasma Pyridoxal-5' Phosphate (PLP) Change From Baseline to Last Obtained Value
Hide Description Effect of asfotase alfa on PLP as measured by change from Baseline to last assessment for each patient
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 56
Median (Full Range)
Unit of Measure: ng/mL
-395.40
(-23836.0 to 2400.0)
10.Secondary Outcome
Title Effect of Asfotase Alfa on Serum Parathyroid Hormone (PTH) - Change From Baseline to Last Obtained Value
Hide Description Effect of asfotase alfa on serum PTH as measured by change from Baseline to last assessment for each patient
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 47
Median (Full Range)
Unit of Measure: pmol/L
0.70
(-4.7 to 5.7)
11.Secondary Outcome
Title Effect of Asfotase Alfa Treatment on Tooth Loss
Hide Description Effect of asfotase alfa treatment on tooth loss assessed by the proportion of patients who experienced tooth loss during the study
Time Frame Up to 72 months or until regulatory approval in the country of residence. Patients received study drug for a median duration of 829.0 days, with a range from 6 to 2116 days (ie, from 0.9 week to 5.8 years).
Hide Outcome Measure Data
Hide Analysis Population Description
Full Analysis Set
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 69
Measure Type: Count of Participants
Unit of Measure: Participants
42
  60.9%
12.Secondary Outcome
Title Pharmacokinetic (PK) Properties of Asfotase Alfa (Tlast)
Hide Description The PK properties (tlast) of asfotase alfa
Time Frame PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
[14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters]
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: hours
48.1  (0.1)
13.Secondary Outcome
Title Pharmacokinetic (PK) Properties of Asfotase Alfa (Tmax)
Hide Description The PK properties (tmax) of asfotase alfa
Time Frame PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: hours
14.9  (10.4)
14.Secondary Outcome
Title Pharmacokinetic (PK) Properties of Asfotase Alfa (Cmax)
Hide Description The PK properties (Cmax) of asfotase alfa
Time Frame PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: ng/mL
1794  (690)
15.Secondary Outcome
Title Pharmacokinetic (PK) Properties of Asfotase Alfa (AUCt)
Hide Description The PK properties (AUCt) of asfotase alfa
Time Frame PK parameters were calculated using Week 6 study visit data. Week 6 study visit blood samples for PK testing were drawn pre-dose and 6, 12, 24, 32, and 48 hours post dose
Hide Outcome Measure Data
Hide Analysis Population Description
14 out of the total 69 subjects had provided sufficient concentration-time data for PK analysis and estimating the PK parameters.
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description:
A total of 6 mg/kg/week of asfotase alfa administered by SC injection (2 mg/kg asfotase alfa 3 times per week)
Overall Number of Participants Analyzed 14
Mean (Standard Deviation)
Unit of Measure: h*ng/mL
66042  (25758)
Time Frame Starting after signing of informed consent through 30 days after the EOS visit, approximately 6 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Asfotase Alfa
Hide Arm/Group Description A total of 6 mg/kg/week of asfotase alfa administered by SC injection (either 1 mg/kg asfotase alfa 6 times per week, or 2 mg/kg asfotase alfa 3 times per week)
All-Cause Mortality
Asfotase Alfa
Affected / at Risk (%)
Total   9/69 (13.04%)    
Hide Serious Adverse Events
Asfotase Alfa
Affected / at Risk (%) # Events
Total   50/69 (72.46%)    
Blood and lymphatic system disorders   
Coagulopathy  1  1/69 (1.45%)  1
Cardiac disorders   
Bradycardia  1  3/69 (4.35%)  10
Cardio-respiratory arrest  1  2/69 (2.90%)  4
Cardiac arrest  1  3/69 (4.35%)  4
Cyanosis  1  2/69 (2.90%)  3
Arrhythmia  1  1/69 (1.45%)  1
Cardiopulmonary failure  1  1/69 (1.45%)  1
Wolff-Parkinson-White syndrome  1  1/69 (1.45%)  1
Congenital, familial and genetic disorders   
Craniosynostosis  1  13/69 (18.84%)  13
Arnold-Chiari malformation  1  3/69 (4.35%)  5
Hypophosphatasia  1  1/69 (1.45%)  1
Endocrine disorders   
Hyperparathyroidism tertiary  1  1/69 (1.45%)  1
Eye disorders   
Conjunctivitis  1  1/69 (1.45%)  1
Optic neuropathy  1  1/69 (1.45%)  1
Gastrointestinal disorders   
Vomiting  1  3/69 (4.35%)  4
Gastrooesophageal reflux disease  1  1/69 (1.45%)  1
Inguinal hernia  1  1/69 (1.45%)  1
Pancreatitis acute  1  1/69 (1.45%)  1
Pneumatosis intestinalis  1  1/69 (1.45%)  1
Rectal prolapse  1  1/69 (1.45%)  2
General disorders   
Pyrexia  1  6/69 (8.70%)  14
Irritability  1  2/69 (2.90%)  2
Chills  1  1/69 (1.45%)  1
Device dislocation  1  1/69 (1.45%)  1
Injection site erythema  1  1/69 (1.45%)  2
Oedema  1  1/69 (1.45%)  1
Immune system disorders   
Drug hypersensitivity  1  2/69 (2.90%)  2
Anaphylactoid reaction  1  1/69 (1.45%)  1
Infections and infestations   
Pneumonia  1  8/69 (11.59%)  9
Pneumonia viral  1  3/69 (4.35%)  3
Device related infection  1  2/69 (2.90%)  5
Gastroenteritis  1  2/69 (2.90%)  2
Gastroenteritis rotavirus  1  2/69 (2.90%)  2
Respiratory syncytial virus infection  1  2/69 (2.90%)  2
Rhinovirus infection  1  2/69 (2.90%)  3
Sepsis  1  2/69 (2.90%)  2
Upper respiratory tract infection  1  2/69 (2.90%)  2
Viral infection  1  2/69 (2.90%)  2
Viral upper respiratory tract infection  1  2/69 (2.90%)  2
Adenoviral upper respiratory infection  1  1/69 (1.45%)  1
Bacteraemia  1  1/69 (1.45%)  2
Beta haemolytic streptococcal infection  1  1/69 (1.45%)  1
Bronchiolitis  1  1/69 (1.45%)  1
Bronchitis  1  1/69 (1.45%)  1
Clostridium difficile colitis  1  1/69 (1.45%)  1
Corona virus infection  1  1/69 (1.45%)  1
Enterobacter infection  1  1/69 (1.45%)  1
Gastroenteritis viral  1  1/69 (1.45%)  1
Influenza  1  1/69 (1.45%)  1
Lower respiratory tract infection  1  1/69 (1.45%)  1
Meningitis staphylococcal  1  1/69 (1.45%)  1
Otitis media  1  1/69 (1.45%)  2
Parainfluenzae virus infection  1  1/69 (1.45%)  1
Postoperative wound infection  1  1/69 (1.45%)  1
Pseudomonas infection  1  1/69 (1.45%)  1
Respiratory tract infection  1  1/69 (1.45%)  1
Respiratory tract infection viral  1  1/69 (1.45%)  1
Serratia infection  1  1/69 (1.45%)  1
Serratia sepsis  1  1/69 (1.45%)  1
Staphylococcal infection  1  1/69 (1.45%)  1
Staphylococcal sepsis  1  1/69 (1.45%)  1
Stenotrophomonas infection  1  1/69 (1.45%)  1
Injury, poisoning and procedural complications   
Femur fracture  1  3/69 (4.35%)  3
Feeding tube complication  1  2/69 (2.90%)  6
Abdominal wound dehiscence  1  1/69 (1.45%)  1
Brain herniation  1  1/69 (1.45%)  1
Endotracheal intubation complication  1  1/69 (1.45%)  3
Eye injury  1  1/69 (1.45%)  1
Humerus fracture  1  1/69 (1.45%)  1
Incorrect dose administered  1  1/69 (1.45%)  1
Rib fracture  1  1/69 (1.45%)  1
Investigations   
Oxygen saturation decreased  1  4/69 (5.80%)  14
Aspiration tracheal  1  1/69 (1.45%)  1
CSF pressure  1  1/69 (1.45%)  1
Enterovirus test positive  1  1/69 (1.45%)  1
Hepatic enzyme increased  1  1/69 (1.45%)  1
Human rhinovirus test positive  1  1/69 (1.45%)  1
Neurological examination abnormal  1  1/69 (1.45%)  1
Nuclear magnetic resonance imaging  1  1/69 (1.45%)  1
Respiratory rate increased  1  1/69 (1.45%)  1
Respiratory syncytial virus test positive  1  1/69 (1.45%)  1
Weight decreased  1  1/69 (1.45%)  1
Metabolism and nutrition disorders   
Food intolerance  1  4/69 (5.80%)  5
Failure to thrive  1  2/69 (2.90%)  3
Feeding disorder  1  2/69 (2.90%)  2
Hyponatraemia  1  2/69 (2.90%)  2
Dehydration  1  1/69 (1.45%)  1
Dystrophic calcification  1  1/69 (1.45%)  1
Fluid overload  1  1/69 (1.45%)  1
Hyperkalaemia  1  1/69 (1.45%)  1
Hypernatraemia  1  1/69 (1.45%)  1
Hyperphosphataemia  1  1/69 (1.45%)  1
Hypoalbuminaemia  1  1/69 (1.45%)  1
Hypokalaemia  1  1/69 (1.45%)  1
Hypophagia  1  1/69 (1.45%)  2
Hypervolaemia  1  1/69 (1.45%)  1
Musculoskeletal and connective tissue disorders   
Osteopenia  1  2/69 (2.90%)  3
Arthralgia  1  1/69 (1.45%)  1
Joint contracture  1  1/69 (1.45%)  1
Pain in extremity  1  1/69 (1.45%)  1
Pathological fracture  1  1/69 (1.45%)  1
Nervous system disorders   
Hydrocephalus  1  3/69 (4.35%)  4
Intracranial pressure increased  1  3/69 (4.35%)  3
Syringomyelia  1  3/69 (4.35%)  3
Convulsion  1  2/69 (2.90%)  2
Headache  1  2/69 (2.90%)  2
Brain oedema  1  1/69 (1.45%)  1
Encephalitis  1  1/69 (1.45%)  1
Febrile convulsion  1  1/69 (1.45%)  2
Haemorrhagic stroke  1  1/69 (1.45%)  1
Intracranial hypotension  1  1/69 (1.45%)  1
Motor developmental delay  1  1/69 (1.45%)  1
Motor dysfunction  1  1/69 (1.45%)  1
Neurological symptom  1  1/69 (1.45%)  1
Petit mal epilepsy  1  1/69 (1.45%)  1
Psychiatric disorders   
Breath holding  1  1/69 (1.45%)  1
Staring  1  1/69 (1.45%)  1
Renal and urinary disorders   
Renal failure  1  1/69 (1.45%)  1
Respiratory, thoracic and mediastinal disorders   
Respiratory disorder  1  4/69 (5.80%)  6
Apnoea  1  3/69 (4.35%)  5
Respiratory distress  1  3/69 (4.35%)  4
Respiratory failure  1  3/69 (4.35%)  3
Acute respiratory failure  1  2/69 (2.90%)  3
Atelectasis  1  2/69 (2.90%)  2
Dyspnoea  1  2/69 (2.90%)  8
Pneumonia aspiration  1  2/69 (2.90%)  2
Adenoidal hypertrophy  1  1/69 (1.45%)  1
Asthma  1  1/69 (1.45%)  1
Bronchospasm  1  1/69 (1.45%)  1
Collapse of lung  1  1/69 (1.45%)  2
Hypoxia  1  1/69 (1.45%)  5
Obstructive airways disorder  1  1/69 (1.45%)  1
Pneumonitis  1  1/69 (1.45%)  1
Pulmonary hypertension  1  1/69 (1.45%)  1
Pulmonary oedema  1  1/69 (1.45%)  1
Respiratory arrest  1  1/69 (1.45%)  2
Upper respiratory tract inflammation  1  1/69 (1.45%)  3
Surgical and medical procedures   
Cranial operation  1  1/69 (1.45%)  1
Medical device removal  1  1/69 (1.45%)  1
Tracheal operation  1  1/69 (1.45%)  1
Tracheostomy  1  1/69 (1.45%)  1
Wean from ventilator  1  1/69 (1.45%)  1
Vascular disorders   
Deep vein thrombosis  1  1/69 (1.45%)  1
1
Term from vocabulary, MedDRA (13.0)
Indicates events were collected by systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Asfotase Alfa
Affected / at Risk (%) # Events
Total   68/69 (98.55%)    
Blood and lymphatic system disorders   
Anaemia  1  9/69 (13.04%)  13
Lymphadenopathy  1  5/69 (7.25%)  7
Neutropenia  1  4/69 (5.80%)  4
Cardiac disorders   
Tachycardia  1  6/69 (8.70%)  16
Bradycardia  1  4/69 (5.80%)  7
Congenital, familial and genetic disorders   
Craniosynostosis  1  10/69 (14.49%)  11
Congenital bowing of long bones  1  5/69 (7.25%)  6
Ear and labyrinth disorders   
Cerumen impaction  1  5/69 (7.25%)  11
Eye disorders   
Conjunctivitis  1  8/69 (11.59%)  16
Papilloedema  1  5/69 (7.25%)  8
Gastrointestinal disorders   
Tooth loss  1  41/69 (59.42%)  109
Vomiting  1  30/69 (43.48%)  92
Diarrhoea  1  20/69 (28.99%)  35
Constipation  1  16/69 (23.19%)  37
Gastrooesophageal reflux disease  1  9/69 (13.04%)  10
Abdominal pain  1  7/69 (10.14%)  7
Dental caries  1  7/69 (10.14%)  11
Teething  1  5/69 (7.25%)  10
Toothache  1  5/69 (7.25%)  8
General disorders   
Pyrexia  1  47/69 (68.12%)  131
Injection site erythema  1  33/69 (47.83%)  223
Injection site discolouration  1  12/69 (17.39%)  43
Injection site induration  1  11/69 (15.94%)  44
Injection site haematoma  1  10/69 (14.49%)  22
Injection site pain  1  8/69 (11.59%)  22
Injection site reaction  1  8/69 (11.59%)  13
Injection site swelling  1  7/69 (10.14%)  21
Injection site pruritus  1  6/69 (8.70%)  14
Catheter site erythema  1  5/69 (7.25%)  16
Injection site papule  1  5/69 (7.25%)  91
Injection site rash  1  5/69 (7.25%)  5
Catheter site inflammation  1  4/69 (5.80%)  5
Device occlusion  1  4/69 (5.80%)  8
Injection site atrophy  1  4/69 (5.80%)  15
Irritability  1  4/69 (5.80%)  6
Hepatobiliary disorders   
Hepatomegaly  1  4/69 (5.80%)  4
Infections and infestations   
Nasopharyngitis  1  18/69 (26.09%)  52
Upper respiratory tract infection  1  17/69 (24.64%)  31
Gastroenteritis  1  16/69 (23.19%)  20
Respiratory tract infection  1  16/69 (23.19%)  62
Ear infection  1  13/69 (18.84%)  18
Rhinitis  1  10/69 (14.49%)  17
Bronchitis  1  9/69 (13.04%)  16
Urinary tract infection  1  8/69 (11.59%)  8
Influenza  1  7/69 (10.14%)  8
Pneumonia  1  7/69 (10.14%)  9
Device related infection  1  5/69 (7.25%)  5
Hand-foot-and-mouth disease  1  5/69 (7.25%)  5
Otitis media  1  5/69 (7.25%)  5
Tonsillitis  1  5/69 (7.25%)  5
Gastroenteritis viral  1  4/69 (5.80%)  5
Gastrointestinal infection  1  4/69 (5.80%)  9
Viral upper respiratory tract infection  1  4/69 (5.80%)  4
Injury, poisoning and procedural complications   
Contusion  1  10/69 (14.49%)  21
Fall  1  7/69 (10.14%)  9
Arthropod bite  1  5/69 (7.25%)  5
Procedural pain  1  5/69 (7.25%)  6
Rib fracture  1  5/69 (7.25%)  5
Tooth fracture  1  4/69 (5.80%)  4
Investigations   
Alanine aminotransferase increased  1  6/69 (8.70%)  8
Aspartate aminotransferase increased  1  5/69 (7.25%)  6
Oxygen saturation decreased  1  5/69 (7.25%)  54
Vitamin D decreased  1  4/69 (5.80%)  6
Metabolism and nutrition disorders   
Hypocalcaemia  1  6/69 (8.70%)  8
Hypoglycaemia  1  6/69 (8.70%)  6
Hypokalaemia  1  6/69 (8.70%)  7
Food intolerance  1  4/69 (5.80%)  5
Musculoskeletal and connective tissue disorders   
Pain in extremity  1  11/69 (15.94%)  13
Kyphosis  1  6/69 (8.70%)  10
Knee deformity  1  5/69 (7.25%)  5
Bone disorder  1  4/69 (5.80%)  23
Nervous system disorders   
Headache  1  10/69 (14.49%)  22
Cerebral ventricle dilatation  1  4/69 (5.80%)  6
Psychiatric disorders   
Agitation  1  4/69 (5.80%)  11
Renal and urinary disorders   
Nephrocalcinosis  1  5/69 (7.25%)  5
Respiratory, thoracic and mediastinal disorders   
Cough  1  17/69 (24.64%)  34
Dyspnoea  1  8/69 (11.59%)  30
Use of accessory respiratory muscles  1  7/69 (10.14%)  16
Atelectasis  1  6/69 (8.70%)  12
Respiratory distress  1  6/69 (8.70%)  7
Tachypnoea  1  6/69 (8.70%)  7
Wheezing  1  5/69 (7.25%)  6
Oropharyngeal pain  1  4/69 (5.80%)  6
Rhinorrhoea  1  4/69 (5.80%)  4
Tracheomalacia  1  4/69 (5.80%)  5
Skin and subcutaneous tissue disorders   
Rash  1  11/69 (15.94%)  23
Dermatitis diaper  1  10/69 (14.49%)  18
Dry skin  1  8/69 (11.59%)  10
Eczema  1  7/69 (10.14%)  14
Erythema  1  6/69 (8.70%)  8
Excessive granulation tissue  1  5/69 (7.25%)  6
Granuloma skin  1  4/69 (5.80%)  7
Heat rash  1  4/69 (5.80%)  5
Vascular disorders   
Hypertension  1  4/69 (5.80%)  4
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
Layout table for Results Point of Contact information
Name/Title: Director of Clinical Trials
Organization: Alexion Pharmaceuticals, Inc.
Phone: 475-230-2596
EMail: ClinicalTrials@alexion.com
Layout table for additonal information
Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01176266    
Other Study ID Numbers: ENB-010-10
First Submitted: July 29, 2010
First Posted: August 5, 2010
Results First Submitted: October 3, 2017
Results First Posted: February 26, 2018
Last Update Posted: March 13, 2019