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

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ClinicalTrials.gov Identifier: NCT00744042
Recruitment Status : Completed
First Posted : August 29, 2008
Results First Posted : September 30, 2011
Last Update Posted : April 1, 2019
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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

Condition or disease Intervention/treatment Phase
Hypophosphatasia (HPP) Biological: asfotase alfa Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Multicenter, Open-Label Study of the Safety, Tolerability and Pharmacology of Asfotase Alfa in up to 10 Severely Affected Patients With for the Treatment of Severely Affected Patients With Infantile Hypophosphatasia (HPP)
Study Start Date : September 2008
Actual Primary Completion Date : May 2010
Actual Study Completion Date : May 2010

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
asfotase alfa
asfotase alfa
Biological: asfotase alfa
Other Names:
  • Asfotase Alfa was formerly referred to as ENB-0040
  • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein

Primary Outcome Measures :
  1. Change in Rickets Severity From Baseline to Week 24, Based on Assessment of Skeletal Radiographs Using Radiologic Global Impression of Change (RGI-C) [ Time Frame: 24 weeks ]
    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. Average scores were derived for each patient at each assessment.

Secondary Outcome Measures :
  1. Maximum Serum Concentration of Asfotase Alfa (Cmax) [ Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose) ]
    Maximum serum concentration observed during intensive PK sampling interval.

  2. Time at Maximum Serum Concentration of Asfotase Alfa (Tmax) [ Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose). ]
    Time at maximum serum concentration observed during intensive PK sampling interval.

  3. Area Under Serum Concentration-time Curve to Last Measurable Concentration of Asfotase Alfa (AUCt) [ Time Frame: Study Week 1 (0 to 168 hours post-dose). Study Week 2 and Study Week 3 (0 to 48 hours post-dose). ]
    Area under serum concentration-time curve to last measurable concentration during intensive PK sampling interval.

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 36 Months   (Child)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00744042

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United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, Delaware
Alfred I. duPont Hospital for Children
Wilmington, Delaware, United States, 19803
United States, Missouri
St. John's Hospital
Springfield, Missouri, United States, 65804
United States, Nebraska
University of Nebraska Medical Center, Munroe-Meyer Institute
Omaha, Nebraska, United States, 68114
United States, Tennessee
Vanderbilt Children's Hospital
Nashville, Tennessee, United States, 37232
United States, Wisconsin
St. Vincent Hospital
Green Bay, Wisconsin, United States, 54301
Canada, Manitoba
The University of Manitoba Health Sciences Centre
Winnipeg, Manitoba, Canada, R3A 1S1
United Arab Emirates
Tawam-John Hopkins Hospital
Al Ain, Abu-Dhabi, United Arab Emirates
United Kingdom
Sheffield Children's Hospital
Sheffield, England, United Kingdom, S10 2TH
Royal Belfast Hospital for Sick Children
Belfast, Northern Ireland, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT00744042    
Other Study ID Numbers: ENB-002-08
First Posted: August 29, 2008    Key Record Dates
Results First Posted: September 30, 2011
Last Update Posted: April 1, 2019
Last Verified: March 2019
Keywords provided by Alexion Pharmaceuticals:
Bone Disease
Soft Bones
Low Alkaline Phosphatase
genetic metabolic disorder
alkaline phosphatase
tissue non-specific alkaline phosphatase
Additional relevant MeSH terms:
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Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs