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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00744042
First Posted: August 29, 2008
Last Update Posted: February 22, 2016
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Alexion Pharma GmbH
August 27, 2008
August 29, 2008
May 15, 2011
September 30, 2011
February 22, 2016
September 2008
May 2010   (Final data collection date for primary outcome measure)
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.
  • To assess the efficacy of ENB-0040 in treating the skeletal manifestations of infantile HPP [ Time Frame: Upon Study Completion (6 months - 1 year) ]
  • To determine the safety and tolerability of ENB-0040 given intravenously (IV) in a single dose and subcutaneously (SC) in repeat doses [ Time Frame: Throughout the course of the investigation and upon study completion (6 months - 1 year) ]
Complete list of historical versions of study NCT00744042 on ClinicalTrials.gov Archive Site
  • 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.
  • 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.
  • 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.
  • To assess the pharmacokinetics (PK) of ENB-0040 given IV and SC [ Time Frame: Upon Study Completion (6 months - 1 year) ]
  • To assess the bioavailability of SC ENB-0040 [ Time Frame: Upon Study Completion (6 months - 1 year) ]
Not Provided
Not Provided
 
Safety and Efficacy Study of Asfotase Alfa in Severely Affected Infants With Hypophosphatasia (HPP)
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)
This clinical trial studies the safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP.
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.
Interventional
Phase 1
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hypophosphatasia (HPP)
Biological: asfotase alfa
Other Names:
  • Asfotase Alfa was formerly referred to as ENB-0040
  • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein
asfotase alfa
asfotase alfa
Intervention: Biological: asfotase alfa

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
11
May 2010
May 2010   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
up to 36 Months   (Child)
No
Contact information is only displayed when the study is recruiting subjects
Canada,   United Arab Emirates,   United Kingdom,   United States
 
 
NCT00744042
ENB-002-08
Yes
Not Provided
Not Provided
Alexion Pharma GmbH
Alexion Pharma GmbH
Not Provided
Not Provided
Alexion Pharma GmbH
January 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP