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

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ClinicalTrials.gov Identifier: NCT01205152
Recruitment Status : Completed
First Posted : September 20, 2010
Results First Posted : November 17, 2017
Last Update Posted : March 13, 2019
Sponsor:
Information provided by (Responsible Party):
Alexion Pharmaceuticals

Tracking Information
First Submitted Date  ICMJE September 17, 2010
First Posted Date  ICMJE September 20, 2010
Results First Submitted Date  ICMJE August 14, 2017
Results First Posted Date  ICMJE November 17, 2017
Last Update Posted Date March 13, 2019
Study Start Date  ICMJE April 2009
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 17, 2010)
Skeletal radiograph using a qualitative Radiographic Global Impression of Change (RGI-C) scale [ Time Frame: 24 months ]
The time points will be pre-treatment (Baseline from the 002 study) to Month 24 of the 003 study which represents 30 months of treatment.
Change History Complete list of historical versions of study NCT01205152 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2017)
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 17, 2010)
Pharmacokinetics (PK) using serum PK and trough levels and pharmacodynamics (PD) of plasma inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and serum parathyroid hormone (PTH) as biomarkers for hypophosphatasia (HPP) [ Time Frame: 24 months ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)
Official Title  ICMJE Extension Study of ENB-0040 (Human Recombinant Tissue-Nonspecific Alkaline Phosphatase Fusion Protein) in Severely Affected Infants and Young Children With Hypophosphatasia (HPP)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypophosphatasia
Intervention  ICMJE Biological: asfotase alfa
Other Name: ENB-0040
Study Arms  ICMJE 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
Intervention: Biological: asfotase alfa
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 5, 2017)
10
Original Actual Enrollment  ICMJE
 (submitted: September 17, 2010)
9
Actual Study Completion Date  ICMJE August 2016
Actual Primary Completion Date August 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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)
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 24 Weeks to 42 Months   (Child)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Arab Emirates,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01205152
Other Study ID Numbers  ICMJE ENB-003-08
FD-R-003745-03 ( Other Grant/Funding Number: Office of Orphan Product Development )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Alexion Pharmaceuticals
Study Sponsor  ICMJE Alexion Pharmaceuticals
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Alexion Pharmaceuticals
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP