Extension Study of Protocol ENB-006-09 -Asfotase Alfa Treatment in Children With Hypophosphatasia

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Alexion Pharma International Sarl
ClinicalTrials.gov Identifier:
NCT01203826
First received: September 15, 2010
Last updated: January 24, 2013
Last verified: July 2012
  Purpose

This clinical trial is being conducted to study long term safety and efficacy outcomes in children with hypophosphatasia (HPP) being treated with an investigational study drug called ENB-0040 (Asfotase Alfa).


Condition Intervention Phase
Hypophosphatasia
Biological: Asfotase Alfa
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Extension Study of Protocol ENB-006-09 Evaluating the Long-term Safety and Efficacy 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:
  • Skeletal radiograph using a qualitative Radiographic Global Impression of Change (RGI-C)scale compared to baseline of treatment in ENB-006-09. [ Time Frame: 60 months ] [ Designated as safety issue: No ]
    The time points will be pre-treatment (Baseline from the 006 study) to Month 60 of the 008 study which represents 66 months of treatment.


Enrollment: 12
Study Start Date: April 2010
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Asfotase Alfa
Asfotase Alfa 6 mg/kg/week SC injection for 60 months
Biological: Asfotase Alfa
2 mg/kg SC injection 3 times per week for 60 months or 1mg/kg sc injection 6 times per week for 60 months.
Other Name: human recombinant tissue non-specific alkaline phosphatase fusion protein

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.

  Eligibility

Ages Eligible for Study:   5 Years to 13 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Compliant and satisfactory completion of Enobia-sponsored clinical trial ENB-006-09
  • Written informed consent by parent or other legal guardian prior to any study procedures being performed
  • Parent or other legal guardian willing to comply with study requirements

Exclusion Criteria:

  • Clinically significant disease that precludes study participation, in the Investigator's opinion
  • Treatment with an investigational drug other than Asfotase Alfa
  • Enrollment in any study involving an investigational drug, device, or treatment for HPP
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01203826

Locations
United States, Missouri
Shriner's Hospital for Children
St. Louis, Missouri, United States, 63131
Canada, Manitoba
Children's Hospital Health Sciences Centre
Winnipeg, Manitoba, Canada, R3B 0A6
Sponsors and Collaborators
Alexion Pharma International Sarl
Investigators
Principal Investigator: Michael Whyte, MD Shriners Hospitals for Children
Principal Investigator: Cheryl Greenberg, MD Children's Hospital Health Sciences Centre
  More Information

No publications provided

Responsible Party: Alexion Pharma International Sarl
ClinicalTrials.gov Identifier: NCT01203826     History of Changes
Other Study ID Numbers: ENB-008-10
Study First Received: September 15, 2010
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
rickets
osteomalacia

Additional relevant MeSH terms:
Hypophosphatasia
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases

ClinicalTrials.gov processed this record on April 17, 2014