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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 15, 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
September 17, 2010
September 20, 2010
August 14, 2017
November 15, 2017
November 15, 2017
April 2009
August 2016   (Final data collection date for primary outcome measure)
  • 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.

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.
Complete list of historical versions of study NCT01205152 on ClinicalTrials.gov Archive Site
  • 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.
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 ]
Not Provided
Not Provided
 
Extension Study of Protocol ENB-002-08 - Study of Asfotase Alfa in Infants and Young Children With Hypophosphatasia (HPP)
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).

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.

Interventional
Phase 2
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Hypophosphatasia
Biological: asfotase alfa
Other Name: ENB-0040
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
Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
10
August 2016
August 2016   (Final data collection date for primary outcome measure)

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)
Sexes Eligible for Study: All
24 Weeks to 42 Months   (Child)
No
Contact information is only displayed when the study is recruiting subjects
United Arab Emirates,   United Kingdom,   United States
 
 
NCT01205152
ENB-003-08
FD-R-003745-03 ( Other Grant/Funding Number: Office of Orphan Product Development )
Yes
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Alexion Pharma GmbH
Alexion Pharma GmbH
Not Provided
Not Provided
Alexion Pharma GmbH
October 2017

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