Safety and Efficacy of Asfotase Alfa in Juvenile Patients With Hypophosphatasia (HPP)

This study has been completed.
Information provided by (Responsible Party):
Alexion Pharma GmbH Identifier:
First received: August 3, 2009
Last updated: May 27, 2014
Last verified: May 2014
This clinical trial studied the safety and efficacy of asfotase alfa in children with HPP compared to a historical control group.

Condition Intervention Phase
Hypophosphatasia (HPP)
Biological: asfotase alfa
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging Study of the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) in Children With Hypophosphatasia (HPP)

Resource links provided by NLM:

Further study details as provided by Alexion Pharma GmbH:

Primary Outcome Measures:
  • Number of Patients Showing Radiographic Response After 24 Weeks of Treatment [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    A 7-point RGI-C (radiographic global impression of change) score was used to rate change in rickets severity. Only those patients with a minimum score of +2 indicating substantial healing of rickets) were considered responders. Three pediatric radiologists not affiliated with the conduct of the study performed the ratings.

  • SAEs (Serious Adverse Events) for All Treated Patients [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    All SAEs experienced by treated patients will be reported and classified according to relationship to treatment

Enrollment: 13
Study Start Date: September 2009
Study Completion Date: July 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 2 mg/kg
2 mg/kg subcutaneous injection three times per week.
Biological: asfotase alfa
Either 2 mg/kg or 3 mg/kg subcutaneous injection three times per week for 6 months.
Other Names:
  • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein
  • sALP-Fc-D10
Active Comparator: 3 mg/kg
3 mg/kg subcutaneous injection three times per week.
Biological: asfotase alfa
Either 2 mg/kg or 3 mg/kg subcutaneous injection three times per week for 6 months.
Other Names:
  • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein
  • sALP-Fc-D10

Detailed Description:

Asfotase Alfa was formerly referred to as ENB-0040

Hypophosphatasia (HPP) is a life-threatening, genetic, and ultra-rare metabolic disease characterized by defective bone mineralization and impaired phosphate and calcium regulation that can lead to progressive damage to multiple vital organs, including destruction and deformity of bones, profound muscle weakness, seizures, impaired renal function, and respiratory failure. There are no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.


Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Written informed consent from parent or legal guardian prior to participation
  2. Patients > 5 and < 12 years of age with open growth plates at time of enrollment
  3. Tanner stage of 2 or less indicating pre-pubescence
  4. Documented history of HPP, as evidenced by:

    • Presence of HPP-related rickets on skeletal radiographs of the wrist and knee
    • Serum alkaline phosphatase (ALP) below age-adjusted normal range
    • Plasma PLP at least twice the upper limit of normal
  5. 25(OH) vitamin D level > 20 ng/mL
  6. Ability of patient and parent/guardian to comply with study requirements

Exclusion Criteria:

  1. Serum calcium or phosphorus below age-adjusted normal range
  2. History of sensitivity to any study drug constituent
  3. Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the Investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities
  4. Treatment with an investigational drug within 1 month before start of study drug
  5. Current enrollment in any other study involving an investigational new drug, device, or treatment for HPP (e.g., bone marrow transplantation)
  6. Current evidence of a treatable form of rickets
  7. Prior treatment with bisphosphonates
  8. Bone fracture or orthopedic surgery within the past 12 months that, in the opinion of the Investigator would interfere with the ability of study patient to comply with study protocol
  9. Major congenital abnormality other than those associated with HPP
  Contacts and Locations
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Please refer to this study by its identifier: NCT00952484

United States, Missouri
Shriners Hospital for Children
St. Louis, Missouri, United States, 63131
Canada, Manitoba
Children's Hospital Health Sciences Centre
Winnipeg, Manitoba, Canada, R3A 1S1
Sponsors and Collaborators
Alexion Pharma GmbH
  More Information

Additional Information:
Responsible Party: Alexion Pharma GmbH Identifier: NCT00952484     History of Changes
Other Study ID Numbers: ENB-006-09 
Study First Received: August 3, 2009
Results First Received: May 14, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Alexion Pharma GmbH:
Bone Disease
Soft Bones
Low Alkaline Phosphatase
genetic metabolic disorder
alkaline phosphatase
tissue non-specific alkaline phosphatase

Additional relevant MeSH terms:
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors processed this record on April 27, 2016