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

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01205152
First Posted: September 20, 2010
Last Update Posted: November 17, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Alexion Pharma GmbH
  Purpose

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).


Condition Intervention Phase
Hypophosphatasia Biological: asfotase alfa Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Alexion Pharma GmbH:

Primary Outcome Measures:
  • 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.

  • 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.



Secondary Outcome Measures:
  • 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.

  • 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.

  • 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.

  • 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.

  • 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.


Enrollment: 10
Study Start Date: April 2009
Study Completion Date: August 2016
Primary Completion Date: August 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ENB-0040

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.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   24 Weeks to 42 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01205152


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

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Alexion Pharma GmbH
ClinicalTrials.gov Identifier: NCT01205152     History of Changes
Other Study ID Numbers: ENB-003-08
FD-R-003745-03 ( Other Grant/Funding Number: Office of Orphan Product Development )
First Submitted: September 17, 2010
First Posted: September 20, 2010
Results First Submitted: August 14, 2017
Results First Posted: November 17, 2017
Last Update Posted: November 17, 2017
Last Verified: October 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharma GmbH:
Hypophosphatasia
HPP
Bone disease
Soft bones
Low alkaline phosphatase
Genetic metabolic disorder
Alkaline phosphatase
Tissue non-specific alkaline phosphatase
Rickets
Osteomalacia

Additional relevant MeSH terms:
Hypophosphatasia
Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Immunoglobulin G
Immunologic Factors
Physiological Effects of Drugs