Clinical Trial: Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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 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.

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 treatment on skeletal manifestations of HPP [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale for all treated patients
• Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa [ Time Frame: Up to 72 months or until regulatory approval ]
  Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients

Original Primary Outcome:

• Effect of ENB-0040 treatment on skeletal manifestations of HPP [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  The effect of ENB-0040 on the skeletal manifestations of HPP after 6 months of ENB-0040 treatment will be measured by comparing Screening and Month 6 radiographs of the chest, upper and lower extremities using a qualitative Radiographic Global Impression of Change (RGI-C) scale
• Safety and tolerability of repeated subcutaneous (SC) injections of ENB-0040 [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  The safety and tolerability of ENB-0040 will be assessed by monitoring adverse events and injection-associated reactions, as well as changes in physical examination findings, vital signs, clinical laboratory evaluations (including routine chemistry, hematology and urinalysis, 25(OH) vitamin D and urinary calcium:creatinine ratio), renal ultrasound and funduscopy findings and antibody evaluations. Changes in concomitant medications and therapies, calcium intake and caloric input will also be monitored.

Current Secondary Outcome:

• Effect of asfotase alfa treatment on ventilator-free survival [ Time Frame: Up to 72 months or until regulatory approval ]
  For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving asfotase alfa as compared to an age-matched historical control group
• Effect of asfotase alfa treatment on respiratory function [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa treatment on respiratory function as measured by ventilator status, time on respiratory support (including time on ventilator or supplemental oxygen), ventilator rate or oxygen volume, ventilator pressures, and fraction of inspired oxygen (FiO2) for all treated patients
• Effect of asfotase alfa treatment on physical growth [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa treatment on physical growth as measured by body weight, length, arm span, head circumference, and chest circumference for all treated patients
• Effect of asfotase alfa treatment on tooth loss [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa treatment on tooth loss for all treated patients
• Pharmacokinetic (PK) properties of asfotase alfa [ Time Frame: Up to 72 months or until regulatory approval ]
  The PK properties of asfotase alfa
• Effect of asfotase alfa on biomarkers [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa on plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)
• Effect of asfotase alfa on serum parathyroid hormone (PTH) [ Time Frame: Up to 72 months or until regulatory approval ]
  Effect of asfotase alfa on serum parathyroid hormone (PTH)

Original Secondary Outcome:

• Effect of ENB-0040 treatment on ventilator-free survival [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  For patients under 9 months of age who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator free at 18 months of age will be compared to an age-matched historical control group
• Effect of ENB-0040 treatment on respiratory function [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  Effect of ENB-0040 treatment on respiratory function will be measured by monitoring ventilator status and settings (where applicable).
• Effect of ENB-0040 treatment on physical growth [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  Effect of ENB-0040 treatment on physical growth will be measured by body weight, length, arm span, head circumference, and chest circumference
• Effect of ENB-0040 treatment on tooth loss [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  Tooth loss will be evaluated by counting the number of teeth present at Baseline and the number of teeth gained and lost during the study
• Pharmacokinetic (PK) properties of ENB-0040 [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  The PK properties of ENB-0040 will be evaluated by monitoring ENB-0040 activity in serum
• Effect of ENB-0040 on biomarkers [ Time Frame: Month 12 (Month 18 for participants < 9 months of age at enrollment) ]
  Effect of ENB-0040 will be memasured on the following biomarkers (which are typically abnormal in HPP patients): plasma inorganic pyrophosphate (PPi), plasma pyridoxal-5' phosphate (PLP) and serum parathyroid hormone (PTH)

Dates:
Date Received: July 29, 2010
Date Started: July 2010
Date Completion: July 2016
Last Updated: March 14, 2016
Last Verified: March 2016