safety and efficacy study of asfotase alfa in adolescents and adults with hypophosphatasia (hpp)

Conditions: Hypophosphatasia

Summary: this clinical trial was conducted to study hypophosphatasia (hpp), a bone disorder caused by gene mutations or changes. these gene mutations cause low levels of an enzyme needed to harden bone. the purpose of this study was to test the safety and efficacy of two doses of the study drug called asfotase alfa as compared to a control group to see effects on adolescents and 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 limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Eligibility criteria:
inclusion criteria: patients must meet all of the following inclusion criteria to be eligible for participation in this study: * patients or their legal representative(s) must provide written informed consent prior to undergoing any study-related procedures * patients must be ≥ 13 and ≤ 65 years of age at the time of study enrollment * female patients of childbearing potential and sexually mature males must agree to use a medically acceptable form of birth control; for the purposes of this study, females are considered of non-childbearing potential if they are surgically sterile (i.e., have undergone a total hysterectomy, bilateral salpingo-oophorectomy or tubal ligation) or are post-menopausal, defined as having complete cessation of menstruation for at least 1 year after 45 years of age * patients must have a pre-established clinical diagnosis of hpp as indicated by: * serum alkaline phosphatase (alp) below the age-adjusted normal range * plasma plp at least twice the upper limit of normal (no vitamin b6 administered for at least 1 week prior to determination) * evidence of osteopenia or osteomalacia on skeletal radiographs * patients must have osteomalacia on bone biopsy, characterized by an mlt z-score of +2 or more (results from enb-001-08 may be used) * patients must be willing to comply with study procedures and the visit schedule exclusion criteria: patients will be excluded from participation in this study if they meet any of the following exclusion criteria: * women who are pregnant or lactating * history of sensitivity to tetracycline * serum calcium or phosphate levels below the normal range * serum 25(oh) vitamin d below 20 ng/ml * serum creatinine or parathyroid hormone (pth) levels above the upper limit of normal * medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities * orthopedic surgery within 12 months prior to study entry that may interfere with the ability to perform functional assessments for the study * prior treatment with bisphosphonates within 2 years of study entry for any length of time or for more than 2 years at any time point; for patients with prior bisphosphonate use that is allowed, the bone resorption markers serum c-telopeptide and urine n-telopeptide or urine deoxypyridinoline must also be within the normal range or elevated to be eligible for study participation * treatment with 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 hpp bone disease soft bones low alkaline phosphatase genetic metabolic disorder alkaline phosphatase tissue-specific alkaline phosphatase (tnsalp) rickets osteomalacia