Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)

This study has been completed.
Information provided by (Responsible Party):
Alexion Pharma GmbH Identifier:
First received: August 27, 2008
Last updated: May 27, 2014
Last verified: May 2014

This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.

Condition Intervention Phase
Hypophosphatasia (HPP)
Biological: asfotase alfa
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of ENB-0040 (Enobia's Human Recombinant Tissue Non-specific Alkaline Phosphatase Fusion Protein) in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile 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: 24 weeks ] [ Designated as safety issue: No ]
    A 7-point RGI-C (Radiographic Global Impression of Change) score was used to rate change in rickets severity. Scores ranged from -3 (severe worsening of rickets) to +3 (complete healing of rickets). 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.

  • Number of SAEs (Serious Adverse Events) for All Treated Patients [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
    The number and description of all SAEs experienced by treated patients were reported and classified according to the relationship to treatment

Enrollment: 11
Study Start Date: September 2008
Study Completion Date: May 2010
Primary Completion Date: May 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
asfotase alfa Biological: asfotase alfa
Other Names:
  • Asfotase Alfa was formerly referred to as ENB-0040
  • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein

Detailed Description:

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:   up to 36 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Legal guardian(s) must provide informed consent prior to any study procedures
  • Documented diagnosis of severe HPP as indicated by:

    • Total serum alkaline phosphatase at least 3 standard deviations (SD) below the mean for age
    • Plasma pyridoxal 5'-phosphate (PLP) at least 4 times the upper limit of normal
    • Radiographic evidence of HPP (hypophosphatasia), characterized by:

      • Flared and frayed metaphyses
      • Severe, generalized osteopenia
      • Widened growth plates
    • One or more HPP-related findings:

      • History or presence of:

        • Non-traumatic post-natal fracture
        • Delayed fracture healing
      • History of elevated serum calcium
      • Functional craniosynostosis with decreased head circumference growth
      • Nephrocalcinosis
      • Respiratory compromise
    • Rachitic chest deformity and/or vitamin B6 dependent seizures
    • Failure to thrive
  • Onset of symptoms prior to 6 months of age
  • Age ≤ 36 months
  • Otherwise medically stable (patient may be on ventilatory support)
  • Legal guardian(s) must be willing to comply with the study

Exclusion Criteria:

  • History of sensitivity to any of the constituents of the study drug
  • Current or prior clinically significant cardiovascular, endocrinologic, hematologic, hepatic, immunologic, metabolic, infectious, urologic, pulmonary, neurologic, dermatologic, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation
  • Treatment with an investigational drug within 1 month prior to the start of study drug administration
  • Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
  • Low serum calcium, phosphate or 25(OH) vitamin D
  • Current evidence of a treatable form of rickets
  • Prior treatment with bisphosphonate
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00744042

United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, Delaware
Nemours/Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Missouri
St. John's Children's Hospital
Springfield, Missouri, United States, 65804
United States, Nebraska
University of Nebraska Children's Hospital & Medical Center
Omaha, Nebraska, United States, 68114
United States, Tennessee
Children's Hospital at Vanderbilt
Nashville, Tennessee, United States, 37232
United States, Wisconsin
St. Vincent Hospital
Green Bay, Wisconsin, United States, 54301
Canada, Manitoba
Department of Pediatrics & Child Health, Health Sciences Centre Winnipeg, University of Manitoba
Winnipeg, Manitoba, Canada, R3A 1S1
United Arab Emirates
Tawam Hospital
Al Ain, Abu-Dhabi, United Arab Emirates
United Kingdom
Sheffield Children's Hospital
Sheffield, England, United Kingdom, S10 2TH
Sponsors and Collaborators
Alexion Pharma GmbH
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Alexion Pharma GmbH Identifier: NCT00744042     History of Changes
Other Study ID Numbers: ENB-002-08
Study First Received: August 27, 2008
Results First Received: May 15, 2011
Last Updated: May 27, 2014
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United Arab Emirates: General Authority for Health Services for Abu Dhabi

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 October 02, 2015