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

March 11, 2019 updated by: Alexion Pharmaceuticals

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

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).

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Arab Emirates
    • Abu-Dhabi
      • Al Ain, Abu-Dhabi, United Arab Emirates
        • Tawam Hospital
  • United Kingdom
      • Sheffield, United Kingdom, S10 2TH
        • Sheffield Children's Hospital
    • Northern Ireland
      • Belfast, Northern Ireland, United Kingdom, Bt126BB
        • Royal Maternity Hospital, Royal Belfast Hospital for Sick Children
  • United States
    • Delaware
      • Wilmington, Delaware, United States, 19803
        • Alfred I. DuPont Hospital for Children
    • Missouri
      • Springfield, Missouri, United States, 65807
        • St. John's Medical Research Institute
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • University of Nebraska Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37232
        • Vanderbilt University Medical Center
    • Wisconsin
      • Green Bay, Wisconsin, United States, 54301
        • St. Vincent Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 months to 3 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 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
Biological: asfotase alfa
Other Names:
  • ENB-0040

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long-term Tolerability of Subcutaneous (SC) Asfotase Alfa
Time Frame: 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.
84 months
Long-term Efficacy of Asfotase Alfa in Treating Rickets in Infants and Young Children With Hypophosphatasia (HPP).
Time Frame: 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.
Up to 90 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Plasma Inorganic Pyrophosphate (PPi) Levels
Time Frame: 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.
Up to 90 Months
Long-term Pharmacodynamics (PD) of SC Asfotase Alfa: Pyridoxal-5-phosphate (PLP) Levels
Time Frame: 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.
Up to 90 Months
Effect of SC Asfotase Alfa on Growth: Weight Z-scores
Time Frame: 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.
Up to 90 Months
Effect of SC Asfotase Alfa on Growth: Height/Length Z-scores
Time Frame: 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.
Up to 90 Months
Effect of SC Asfotase Alfa on Respiratory Function
Time Frame: 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.
Up to 90 Months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion Pharmaceuticals

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2009

Primary Completion (Actual)

August 1, 2016

Study Completion (Actual)

August 1, 2016

Study Registration Dates

First Submitted

September 17, 2010

First Submitted That Met QC Criteria

September 17, 2010

First Posted (Estimate)

September 20, 2010

Study Record Updates

Last Update Posted (Actual)

March 13, 2019

Last Update Submitted That Met QC Criteria

March 11, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENB-003-08
  • FD-R-003745-03 (Other Grant/Funding Number: Office of Orphan Product Development)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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