Extension Study of Protocol ENB-006-09 -Asfotase Alfa Treatment in Children With Hypophosphatasia
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).
|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)|
- 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.
|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)|
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
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.
|United States, Missouri|
|Shriner's Hospital for Children|
|St. Louis, Missouri, United States, 63131|
|Children's Hospital Health Sciences Centre|
|Winnipeg, Manitoba, Canada, R3B 0A6|
|Principal Investigator:||Michael Whyte, MD||Shriners Hospitals for Children|
|Principal Investigator:||Cheryl Greenberg, MD||Children's Hospital Health Sciences Centre|