Safety Study of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein (ENB-0040) in Adults With Hypophosphatasia (HPP)

The purpose of this Phase I study is to test the safety of Human Recombinant Tissue Non-Specific Alkaline Phosphatase Fusion Protein (ENB-0040) and see what effects it has on humans and Hypophosphatasia (HPP). The study will also look at differences in injecting the drug into a vein with a needle (intravenously) and injecting it under the surface of the skin (subcutaneously)

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.

Refer to ClinicalTrials.gov identifier NCT00739505