Overview

This trial is active, not recruiting.

Condition hypophosphatasia
Treatment asfotase alfa
Phase phase 2/phase 3
Sponsor Alexion Pharma GmbH
Start date July 2010
End date July 2016
Trial size 69 participants
Trial identifier NCT01176266, ENB-010-10

Summary

This clinical trial is being 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 is to test the safety and efficacy of a study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate fusion protein) to see what effects it has on patients ≤ 5 years of age or less with HPP.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Experimental)
asfotase alfa

Primary Outcomes

Measure
Effect of asfotase alfa treatment on skeletal manifestations of HPP
time frame: Up to 72 months or until regulatory approval
Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa
time frame: Up to 72 months or until regulatory approval

Secondary Outcomes

Measure
Effect of asfotase alfa treatment on ventilator-free survival
time frame: Up to 72 months or until regulatory approval
Effect of asfotase alfa treatment on respiratory function
time frame: Up to 72 months or until regulatory approval
Effect of asfotase alfa treatment on physical growth
time frame: Up to 72 months or until regulatory approval
Effect of asfotase alfa treatment on tooth loss
time frame: Up to 72 months or until regulatory approval
Pharmacokinetic (PK) properties of asfotase alfa
time frame: Up to 72 months or until regulatory approval
Effect of asfotase alfa on biomarkers
time frame: Up to 72 months or until regulatory approval
Effect of asfotase alfa on serum parathyroid hormone (PTH)
time frame: Up to 72 months or until regulatory approval

Eligibility Criteria

Male or female participants up to 5 years old.

Inclusion Criteria: Patients must meet all of the following criteria for enrollment in this study: - Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures - Documented diagnosis of HPP as indicated by: - Total serum alkaline phosphatase below the lower limit of normal for age - Plasma PLP above the upper limit of normal (unless patient is receiving pyridoxine for seizures) - Radiographic evidence of HPP, characterized by: - Flared and frayed metaphyses - Severe, generalized osteopenia - Widened growth plates - Areas of radiolucency or sclerosis - Two or more of the following HPP-related findings: - History or presence of: - Nontraumatic post-natal fracture - Delayed fracture healing - Nephrocalcinosis or history of elevated serum calcium - Functional craniosynostosis - Respiratory compromise or rachitic chest deformity - Vitamin B6 dependent seizures - Failure to thrive - Onset of symptoms prior to 6 months of age - Chronological age or adjusted age for premature infants born ≤ 37 weeks gestation of ≤ 5 years - Otherwise medically stable in the opinion of the Investigator and/or Sponsor - Patients with low 25(OH) vitamin D levels are eligible for study participation after correction of levels with vitamin D supplementation. Exclusion criteria: Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria: - Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor - Serum calcium or phosphate levels below the normal range - Current evidence of treatable form of rickets - Prior treatment with bisphosphonates - Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment - Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation) - Intolerance to the IP or any of its excipients - Previous participation in the same study - Family relative of the Investigator NOTE: Historical values for PLP may be used to determine patient eligibility.

Additional Information

Official title An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)
Description 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.
Trial information was received from ClinicalTrials.gov and was last updated in March 2016.
Information provided to ClinicalTrials.gov by Alexion Pharma GmbH.