Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)

Phase 2

Completed

Conditions: Hypophosphatasia

Interventions: Biological: asfotase alfa

Registration Number: NCT01205152

Lead Sponsor: Alexion Pharmaceuticals, Inc.

Brief Summary: This clinical trial studied the long term safety and efficacy of asfotase alfa in infants and young children with infantile onset HPP who completed study ENB-002-08 (NCT00744042).

Partial funding for this study was provided by the Office of Orphan Product Development (OOPD).

Detailed 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 limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
asfotase alfa	asfotase alfa	An initial single intravenous (IV) infusion of 2 mg/kg asfotase alfa, followed by subcutaneous (SC) injections of 1 mg/kg asfotase alfa 3 times per week

Primary Outcome Measures

Name	Time	Method
Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa	84 months	Outcome measure is the number of patients with 1 or more treatment-emergent adverse event. The time period is from Baseline in the ENB-003-08 study to the end of the ENB-003-08 study.
Long-term Efficacy of Asfotase Alfa in Treating Rickets in Infants and Young Children With Hypophosphatasia (HPP).	Up to 90 Months	Outcome measure is the evaluation of radiographic change in rickets severity using a qualitative Radiographic Global Impression of Change (RGI-C) Scale. Skeletal radiographs obtained at the patient's last assessment were compared with skeletal radiographs obtained before initiation of treatment (Baseline in Study ENB-002-08 \[NCT00744042\]). The RGI-C is a 7-point rating scale that ranges from -3 (indicative of severe worsening of HPP-associated rickets) to +3 (indicative of complete or near complete healing of HPP-associated rickets). The time period is pre-dose (Baseline from ENB-002-08 study) to the last assessment for each patient in the ENB-003-08 study, which represents up to 90 months of exposure for the combined studies.

Secondary Outcome Measures

Name	Time	Method
Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Plasma Inorganic Pyrophosphate (PPi) Levels	Up to 90 Months	Outcome measure is the change from Baseline in plasma inorganic pyrophosphate (PPi) levels. The time period is pre-dose (Baseline from the ENB-002-08 study \[NCT00744042\]) to the last assessment for each patient in the ENB-003-08 study, which represents up to 90 months of exposure for the combined studies.
Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Pyridoxal-5-phosphate (PLP) Levels	Up to 90 Months	Outcome measure is the change from Baseline in pyridoxal-5-phosphate (PLP) levels. The time period is pre-dose (Baseline from the ENB-002-08 study \[NCT00744042\]) to the last assessment for each patient in the ENB-003-08 study, which represents up to 90 months of exposure for the combined studies.
Effect of SC Asfotase Alfa on Growth: Weight Z-scores	Up to 90 Months	Outcome measure is the change from Baseline in Z-scores for weight. The time period is pre-dose (Baseline from the ENB-002-08 study \[NCT00744042\]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.
Effect of SC Asfotase Alfa on Growth: Height/Length Z-scores	Up to 90 Months	Outcome measure is the change from Baseline in Z-scores for height/length. The time period is pre-dose (Baseline from the ENB-002-08 study \[NCT00744042\]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.
Effect of SC Asfotase Alfa on Respiratory Function	Up to 90 Months	Outcome measure is the shift in the proportion of patients requiring respiratory support at their last assessment in Study ENB-003-08 compared with Baseline. The time period is pre-dose (Baseline from the ENB-002-08 study \[NCT00744042\]) to the last assessment in the ENB-003-08 study, which represents up to 90 months of exposure in the combined studies.

Trial Locations

Locations (8): Alfred I. DuPont Hospital for Children
🇺🇸
Wilmington, Delaware, United States
St. Vincent Hospital
🇺🇸
Green Bay, Wisconsin, United States
University of Nebraska Medical Center
🇺🇸
Omaha, Nebraska, United States
St. John's Medical Research Institute
🇺🇸
Springfield, Missouri, United States
Vanderbilt University Medical Center
🇺🇸
Nashville, Tennessee, United States
Sheffield Children's Hospital
🇬🇧
Sheffield, United Kingdom
Tawam Hospital
🇦🇪
Al Ain, Abu-Dhabi, United Arab Emirates
Royal Maternity Hospital, Royal Belfast Hospital for Sick Children
🇬🇧
Belfast, Northern Ireland, United Kingdom