Clinical Trial: Safety and Efficacy Study of Asfotase Alfa in Adolescents and Adults With Hypophosphatasia (HPP)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Randomized, Open-Label, Multicenter, Multinational, Dose-Ranging, Concurrent Control Study of the Safety, Efficacy, Pharmacokinetic of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phospha

Brief 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 two doses of the study drug called asfotase alfa as compared to a control group to see what effects it has adolescents and adults with HPP.

Detailed Summary:

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.

Current Primary Outcome:

• Effect of asfotase alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) [ Time Frame: Week 24 ]
  Blood samples will be collected to evaluate the effect of Asfotase Alfa on reduction in plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
• Safety and Tolerability of asfotase alfa [ Time Frame: Up to 96 weeks or until regulatory approval ]
  The safety and tolerability of daily subcutaneous (SC) injections of asfotase alfa will be assessed by routine monitoring of patients for adverse events (AEs) and injection-associated reactions (IARs) and monitoring changes from Baseline in physical examination findings, vital signs, clinical laboratory evaluations, renal ultrasound findings, funduscopic examinations, antibody evaluations, and results of pregnancy testing (in women of childbearing potential only). Monitoring for changes in concomitant medications and therapies will also occur.

Original Primary Outcome:

• Effect of ENB-0040 on HPP-related osteomalacia [ Time Frame: Two bone biopsies will be performed - pre-treatment and 6 months post-treatment ]
  The effect of ENB-0040 on HPP-related osteomalacia will be measured using trans-iliac crest bone biopsy by comparing results from the two treatment cohorts to the concurrent control cohort
• Safety and Tolerability of ENB-0040 [ Time Frame: Continuous monitoring for 6-month duration of study ]
  The safety and tolerability of daily subcutaneous (SC) injections of ENB-0040 will be assessed by routine monitoring of patients for adverse events (AEs) and injection-associated reactions (IARs) and monitoring changes from Baseline in physical examination findings, vital signs, clinical laboratory evaluations, renal ultrasound findings, funduscopic examinations, antibody evaluations, and results of pregnancy testing (in women of childbearing potential only).

Current Secondary Outcome:

• Change in bone mineral content and density as measured by dual-energy X-ray absorptiometry (DXA) [ Time Frame: Every 24 weeks ]
  A DXA scan will be performed to evaluate bone mineral content and density of the spine, hip, and whole body.
• Change in walking ability as measured by the Six-Minute Walk Test (6MWT) [ Time Frame: Every 24 weeks ]
  The patient will be instructed to walk the length of a pre-measured hallway for 6 minutes. The primary measurement will be the distance walked (in meters).
• Change in HPP-related osteomalacia as measured by trans-iliac crest bone biopsy [ Time Frame: Week 24, Week 48 ]
  A trans-iliac crest bone biopsy will be performed to quantify osteomalacia severity.

Original Secondary Outcome:

• Effect of ENB-0040 on walking ability [ Time Frame: Pre-treatment and 3 months and 6 months post-treatment ]
  Effect of ENB-0040 on walking ability as measured by the Six Minute Walk Test (6MWT)
• Effect of ENB-0040 on gross motor function [ Time Frame: Pre-treatment and 3 months and 6 months post-treatment ]
  The effect of ENB-0040 on gross motor function as measured by a modified version of the Bruininks-Oseretsky Test of Motor Proficiency - Second Edition (BOT-2)
• Effect of ENB-0040 on pain [ Time Frame: Pre-treatment and 3 months and 6 months post-treatment ]
  Change in self-reported pain as measured by a modified version of the Brief Pain Inventory - Short Form (BPI-SF)
• Change in biomarkers of ENB-0040 activity [ Time Frame: Pre-treatment and 6 weeks, 3 months and 6 months post-treatment ]
  Change in biomarkers of ENB-0040 activity as measured by plasma inorganic pyrophosphate (PPi), plasma pyridoxal-5'-phosphate (PLP) and serum parathyroid hormone (PTH)

Dates:
Date Received: June 24, 2010
Date Started: June 2010
Date Completion:
Last Updated: August 3, 2016
Last Verified: August 2016