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

This study has been completed.
Information provided by (Responsible Party):
Alexion Pharma International Sarl Identifier:
First received: August 3, 2009
Last updated: January 24, 2013
Last verified: December 2011

This clinical trial is being conducted to study Hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study is to test the safety of the study drug called Asfotase Alfa and see what effects it has on human juveniles and HPP.

Condition Intervention Phase
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 Asfotase Alfa (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 International Sarl:

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 rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The prevalence of the disease is thought to be about 1:100,000 although it is markedly higher in a small Canadian Mennonite population (Fraser 1957, Chodirker 1990). Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a wide range of clinical expressivity. HPP differs from other forms of rickets and osteomalacia in that serum levels of calcium and phosphorus are generally normal or even elevated (Whyte 2002). Low circulating levels of alkaline phosphatase with elevated serum or urine levels of the TNSALP substrates inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA) are the biochemical hallmarks of this inborn error of metabolism.

Disease severity in HPP is inversely related to the age at symptom presentation. The most severe cases occur in utero and almost invariably result in death, generally due to pulmonary compromise. Infants who present in the first six months of life have about 50% mortality. Children and adults have less severe disease but can have frequent fractures, bone pain, bowing of the long bones and muscle weakness, and morbidity is generally cumulative. Some patients cannot ambulate independently and end up wheelchair-bound.


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
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 International Sarl
Principal Investigator: Michael P Whyte, MD Shriners Hospital, St. Louis. MO
Principal Investigator: Cheryl R Greenberg, MD Children's Hospital Health Sciences Centre, Winnipeg, Canada
  More Information

Additional Information:
Responsible Party: Alexion Pharma International Sarl 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: January 24, 2013
Health Authority: United States: Food and Drug Administration
Canada: Health Canada

Keywords provided by Alexion Pharma International Sarl:
genetic metabolic disorder
alkaline phosphatase
tissue non-specific alkaline phosphatase

Additional relevant MeSH terms:
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases processed this record on April 15, 2014