ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: 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

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
0.3 mg/kg Asfotase Alfa

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.

0.5 mg/kg Asfotase Alfa

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.

Concurrent Control

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.


Participant Flow for 2 periods

Period 1:   Primary Treatment Period
    0.3 mg/kg Asfotase Alfa   0.5 mg/kg Asfotase Alfa   Concurrent Control
STARTED   7   6   6 
COMPLETED   7   6   6 
NOT COMPLETED   0   0   0 

Period 2:   Extension Treatment Period
    0.3 mg/kg Asfotase Alfa   0.5 mg/kg Asfotase Alfa   Concurrent Control
STARTED   7   6   6 
COMPLETED   5   5   4 
NOT COMPLETED   2   1   2 
Withdrawal by Subject                2                0                1 
Adverse Event                0                1                0 
Noncompliance                0                0                1 



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
All efficacy analyses were performed on the full analysis set (intent-to-treat population), which consisted of all randomized patients (n=19).

Reporting Groups
  Description
0.3 mg/kg Asfotase Alfa

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.

0.5 mg/kg Asfotase Alfa

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.

Concurrent Control

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 Total of all reporting groups

Baseline Measures
   0.3 mg/kg Asfotase Alfa   0.5 mg/kg Asfotase Alfa   Concurrent Control   Total 
Overall Participants Analyzed 
[Units: Participants]
 7   6   6   19 
Age 
[Units: Years]
Median (Full Range)
 45.0 
 (14 to 66) 
 55.0 
 (15 to 57) 
 21.0 
 (13 to 58) 
 53.0 
 (13 to 66) 
Age, Customized 
[Units: Years]
Median (Full Range)
       
Age at Onset of Symptoms   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 
[Units: Participants]
Count of Participants
       
Age Group         
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 
[Units: Participants]
Count of 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) 
[Units: Participants]
Count of 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) 
[Units: Participants]
Count of 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 
[Units: Participants]
Count of 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% 


  Outcome Measures

1.  Primary:   Change From Baseline to Week 24 for Plasma Pyridoxal-5' Phosphate (PLP)   [ Time Frame: Baseline, Week 24 ]

2.  Primary:   Change From Baseline to Week 24 for Plasma Inorganic Pyrophosphate (PPi)   [ Time Frame: Baseline, Week 24 ]

3.  Primary:   Safety and Tolerability of Asfotase Alfa   [ Time Frame: Up to 288 weeks exposure to asfotase alfa ]

4.  Secondary:   Change From Baseline in Bone Mineral Content (BMC) as Measured by Dual-energy X-ray Absorptiometry (DXA)   [ Time Frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288. ]

5.  Secondary:   Change From Baseline in Bone Mineral Density (BMD) as Measured by Dual-energy X-ray Absorptiometry (DXA)   [ Time Frame: Baseline, every 24 weeks through Week 96, then every 48 weeks until Week 288. ]

6.  Secondary:   Change in Walking Ability as Measured by the Six-Minute Walk Test (6MWT)   [ Time Frame: Baseline, Week 24 (primary treatment period) and up to 288 weeks of asfotase alfa exposure ]

7.  Secondary:   Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Volume/Bone Volume   [ Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). ]

8.  Secondary:   Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Osteoid Thickness   [ Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). ]

9.  Secondary:   Change From Baseline in HPP-related Osteomalacia as Measured by Trans-iliac Crest Bone Biopsy: Mineralization Lag Time   [ Time Frame: Baseline, Week 24 (Control group), and Week 48 (Asfotase alfa groups). ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI 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
e-mail: ClinicalTrials@alexion.com


Publications:

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