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

Hypophosphatasia Clinical Trial

Official title:

Extension Study of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Severely Affected Infants and Young Children With Hypophosphatasia (HPP)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01205152
• Other study ID #: ENB-003-08
• Secondary ID: FD-R-003745-03
• Status: Completed
• Phase: Phase 2
• Start date: April 2009
• Est. completion date: August 2016

Study information

• Verified date: March 2019
• Source: Alexion Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Completed
• Enrollment: 10
• Est. completion date: August 2016
• Est. primary completion date: August 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 24 Weeks to 42 Months

Eligibility

Inclusion Criteria

• Patient completed participation in ENB-002-08 (NCT00744042)

• Written informed consent by parent or other legal guardian prior to any study procedures being performed

• Parent or other legal guardian willing to comply with study requirements

Exclusion Criteria

• History of sensitivity to any of the constituents of the study drug

• Clinically significant disease that precludes study participation

• Enrollment in any study (other than ENB-002-08) involving an investigational drug, device, or treatment for HPP (e.g., bone marrow transplantation)

Related Conditions & MeSH terms

• Hypophosphatasia

Intervention

Biological:
• asfotase alfa

Locations

Country	Name	City	State
United Arab Emirates	Tawam Hospital	Al Ain	Abu-Dhabi
United Kingdom	Royal Maternity Hospital, Royal Belfast Hospital for Sick Children	Belfast	Northern Ireland
United Kingdom	Sheffield Children's Hospital	Sheffield
United States	St. Vincent Hospital	Green Bay	Wisconsin
United States	Vanderbilt University Medical Center	Nashville	Tennessee
United States	University of Nebraska Medical Center	Omaha	Nebraska
United States	St. John's Medical Research Institute	Springfield	Missouri
United States	Alfred I. DuPont Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Alexion Pharmaceuticals

Countries where clinical trial is conducted

United States,  United Arab Emirates,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa	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.	84 months
Primary	Long-term Efficacy of Asfotase Alfa in Treating Rickets in Infants and Young Children With Hypophosphatasia (HPP).	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.	Up to 90 Months
Secondary	Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Plasma Inorganic Pyrophosphate (PPi) Levels	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.	Up to 90 Months
Secondary	Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Pyridoxal-5-phosphate (PLP) Levels	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.	Up to 90 Months
Secondary	Effect of SC Asfotase Alfa on Growth: Weight Z-scores	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.	Up to 90 Months
Secondary	Effect of SC Asfotase Alfa on Growth: Height/Length Z-scores	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.	Up to 90 Months
Secondary	Effect of SC Asfotase Alfa on Respiratory Function	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.	Up to 90 Months

External Links

•   HPP support group
•   Hypophosphatasia Website
•   Hypophosphatasia Website for Healthcare Providers
•   Hypophosphatasie Europe
•   US Hypophosphatasia Group (Soft Bones)