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 International Sarl Identifier:
First received: August 27, 2008
Last updated: January 24, 2013
Last verified: December 2011

This Clinical Trial is being conducted to study the safety and efficacy of an investigational drug Asfotase Alfa for the treatment of infants with hypophosphatasia (HPP).

Condition Intervention Phase
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: Study of Asfotase Alfa (Human Recombinant Tissue Non-specific Alkaline Phosphatase Fusion Protein) for the Treatment of Severely Affected Patients With Infantile 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: 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 pateints 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
All patients receive a single IV (intravenous) dose of 2 mg/kg followed by 7 days of observation. Patients then begin thrice weekly SC (subcutaneous) injections of Asfotase Alfa at a dose of 1 mg/kg for 23 weeks. The total duration of the study is 24 weeks.
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 rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). 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 the disease. 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.


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
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 International Sarl
Principal Investigator: Cheryl Rockman-Greenberg, MD The University of Manitoba Health Sciences Centre, Winnipeg MB Canada
Principal Investigator: Jill H Simmons, MD Vanderbilt Children's Hospital, Nashville TN USA
Principal Investigator: Martin L Bauer, MD Arkansas Children's Hospital, Little Rock AR USA
Principal Investigator: Nick Bishop, MD Sheffield Children's Hospital, Sheffield Great Britain UK
Principal Investigator: Terrance S Edgar, MD St. VIncent's Hospital, Green Bay WI USA
Principal Investigator: Nada J Salman, MD Tawam-Johns Hopkins Hospital, Al Ain Abu-Dhabi UAE
Principal Investigator: Stanley Craig, MD Royal Belfast Hospital for Sick Children, Belfast Northern Ireland UK
Principal Investigator: Michael B Bober, MD Alfred I. duPont Hospital for Children, Wilmington DE USA
Principal Investigator: Jean N Moore, MD St. John's Hospital, Springfield MO USA
Principal Investigator: Richard E Lutz, MD University of Nebraska Medical Center, Omaha NE USA
  More Information

Additional Information:
Additional publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Alexion Pharma International Sarl 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: 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 16, 2014