safety study of human recombinant tissue non-specific alkaline phosphatase fusion protein asfotase alfa in adults with hypophosphatasia (hpp)

Conditions: Hypophosphatasia (HPP)

Summary: this clinical trial studies the safety, tolerability, and pharmacology of asfotase alfa when given to adults with hpp.

asfotase alfa was formerly referred to as enb-0040 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.

Eligibility criteria:
inclusion criteria: in order to qualify for participation, patients must meet all of the following criteria: * patients must provide written informed consent, including privacy authorization, prior to participation. * women of childbearing potential must sign the women of childbearing potential addendum and must be using an acceptable method of birth control. women considered not of childbearing potential must be surgically sterile (total hysterectomy, bilateral salpingo-oophorectomy, or tubal ligation) or post-menopausal, which is defined as a complete cessation of menstruation for at least one year after the age of 45 years. all women must have a serum pregnancy test conducted at screening prior to enrollment and the results must be negative. * be between 18 and 80 years of age at the time of consent * patients must be medically stable in the opinion of the investigator. * patients must be willing to comply with study procedures and the visit schedule. * pre-established clinical diagnosis of hpp as indicated by: * a. serum alkaline phosphatase at least 3 sd below the mean for age * b. radiologic evidence of osteopenia or osteomalacia * c. two or more hpp-related findings: * i. plasma pyridoxal 5'-phosphate at least 2.5 sd above the mean (no vitamin b6 administered for at least 1 week prior to determination * ii. history of rickets * iii. history of premature loss of deciduous teeth * iv. bone deformity consistent with osteomalacia or past history of rickets * v. history of any one of the following: * 1. non-traumatic fracture * 2. pseudofracture * 3. non-healing fracture exclusion criteria: in order to qualify for participation, patients must not meet any of the following criteria: * women who are pregnant or lactating. * history of sensitivity to any of the constituents of the study drug. * low levels of serum calcium, magnesium or phosphate. * serum 25(oh) vitamin d level below 9.2 ng/ml. * elevated serum creatinine or parathyroid hormone level. * known cause of hypophosphatasemia other than hpp. * current or prior clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, renal condition and/or other major disease which, in the opinion of the investigator, precludes study participation. * treatment with a bisphosphonate or parathyroid hormone (pth) within 6 months prior to the start of asfotase alfa administration. * participation in an interventional or investigational drug study within 30 days prior to study participation.

Keywords: hypophosphatasia bone disease soft bones low alkaline phosphatase genetic metabolic disorder alkaline phosphatase tissue non-specific alkaline phosphatase rickets osteomalacia