Open-Label Study of Asfotase Alfa in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2015 by Alexion Pharma International Sarl
Sponsor:
Information provided by (Responsible Party):
Alexion Pharma International Sarl
ClinicalTrials.gov Identifier:
NCT01176266
First received: July 29, 2010
Last updated: July 9, 2015
Last verified: July 2015
  Purpose

This clinical trial is being conducted to study hypophosphatasia (HPP), a bone disorder caused by gene mutations or changes. These gene mutations cause low levels of an enzyme needed to harden bone. The purpose of this study is to test the safety and efficacy of a study drug called asfotase alfa (human recombinant tissue non-specific alkaline phosphate fusion protein) to see what effects it has on patients ≤ 5 years of age or less with HPP.


Condition Intervention Phase
Hypophosphatasia
Drug: asfotase alfa
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multicenter, Multinational Study of the Safety, Efficacy and Pharmacokinetics of Asfotase Alfa (Human Recombinant Tissue-nonspecific Alkaline Phosphatase Fusion Protein) in Infants and Children ≤ 5 Years of Age With Hypophosphatasia (HPP)

Resource links provided by NLM:


Further study details as provided by Alexion Pharma International Sarl:

Primary Outcome Measures:
  • Effect of asfotase alfa treatment on skeletal manifestations of HPP [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa treatment on skeletal manifestations of HPP as measured by radiographs using a qualitative Radiographic Global Impression of Change (RGI-C) scale for all treated patients

  • Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: Yes ]
    Safety and tolerability of repeated subcutaneous (SC) injections of asfotase alfa for all treated patients


Secondary Outcome Measures:
  • Effect of asfotase alfa treatment on ventilator-free survival [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    For patients who are not mechanically ventilated at the time of enrollment, the percentage who are alive and ventilator-free after receiving asfotase alfa as compared to an age-matched historical control group

  • Effect of asfotase alfa treatment on respiratory function [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa treatment on respiratory function as measured by ventilator status, time on respiratory support (including time on ventilator or supplemental oxygen), ventilator rate or oxygen volume, ventilator pressures, and fraction of inspired oxygen (FiO2) for all treated patients

  • Effect of asfotase alfa treatment on physical growth [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa treatment on physical growth as measured by body weight, length, arm span, head circumference, and chest circumference for all treated patients

  • Effect of asfotase alfa treatment on tooth loss [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa treatment on tooth loss for all treated patients

  • Pharmacokinetic (PK) properties of asfotase alfa [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    The PK properties of asfotase alfa

  • Effect of asfotase alfa on biomarkers [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa on plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP)

  • Effect of asfotase alfa on serum parathyroid hormone (PTH) [ Time Frame: Up to 72 months or until regulatory approval ] [ Designated as safety issue: No ]
    Effect of asfotase alfa on serum parathyroid hormone (PTH)


Estimated Enrollment: 100
Study Start Date: July 2010
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: July 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Single arm Drug: asfotase alfa

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 no approved disease-modifying treatments for patients with this disease. There is also limited data available on the natural course of this disease over time, particularly in patients with the juvenile-onset form.

  Eligibility

Ages Eligible for Study:   up to 5 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Patients must meet all of the following criteria for enrollment in this study:

  • Parent or legal guardian(s) must provide written informed consent prior to any study procedures being performed and must be willing to comply with all study-required procedures
  • Documented diagnosis of HPP as indicated by:

    • Total serum alkaline phosphatase below the lower limit of normal for age
    • Plasma PLP above the upper limit of normal (unless patient is receiving pyridoxine for seizures)
    • Radiographic evidence of HPP, characterized by:

      • Flared and frayed metaphyses
      • Severe, generalized osteopenia
      • Widened growth plates
      • Areas of radiolucency or sclerosis
    • Two or more of the following HPP-related findings:

      • History or presence of:

        • Nontraumatic post-natal fracture
        • Delayed fracture healing
      • Nephrocalcinosis or history of elevated serum calcium
      • Functional craniosynostosis
      • Respiratory compromise or rachitic chest deformity
      • Vitamin B6 dependent seizures
      • Failure to thrive
  • Onset of symptoms prior to 6 months of age
  • Chronological age or adjusted age for premature infants born ≤ 37 weeks gestation of ≤ 5 years
  • Otherwise medically stable in the opinion of the Investigator and/or Sponsor
  • Patients with low 25(OH) vitamin D levels are eligible for study participation after correction of levels with vitamin D supplementation.

Exclusion criteria:

Patients will be excluded from enrollment in this study if they meet any of the following exclusion criteria:

  • Clinically significant disease that precludes study participation, in the opinion of the Investigator and/or Sponsor
  • Serum calcium or phosphate levels below the normal range
  • Current evidence of treatable form of rickets
  • Prior treatment with bisphosphonates
  • Treatment with an investigational drug within 1 month prior to the start of asfotase alfa treatment
  • Current enrollment in any other study involving an investigational new drug, device or treatment for HPP (e.g., bone marrow transplantation)
  • Intolerance to the IP or any of its excipients
  • Previous participation in the same study
  • Family relative of the Investigator

NOTE: Historical values for PLP may be used to determine patient eligibility.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01176266

Contacts
Contact: Alexion Pharma International Sàrl (Sponsor) clinicaltrials@alxn.com

  Show 24 Study Locations
Sponsors and Collaborators
Alexion Pharma International Sarl
  More Information

Additional Information:
No publications provided

Responsible Party: Alexion Pharma International Sarl
ClinicalTrials.gov Identifier: NCT01176266     History of Changes
Other Study ID Numbers: ENB-010-10
Study First Received: July 29, 2010
Last Updated: July 9, 2015
Health Authority: United States: Food and Drug Administration
Canada: Health Canada
Germany: Federal Institute for Drugs and Medical Devices
Taiwan : Food and Drug Administration
Japan: Pharmaceuticals and Medical Devices Agency
Turkey: Drug and Medical Device Institution
Italy: The Italian Medicines Agency
Spain: Agencia Española de Medicamentos y Productos Sanitarios
United Kingdom: Medicines and Healthcare Products Regulatory Agency
France: Agence Nationale de Sécurité du Médicament et des produits de santé
Australia: Department of Health and Ageing Therapeutic Goods Administration

Keywords provided by Alexion Pharma International Sarl:
Hypophosphatasia
HPP
Bone Disease
Soft Bones
Low Alkaline Phosphatase
genetic metabolic disorder
alkaline phosphatase
tissue-specific alkaline phosphatase (TNSALP)
rickets
osteomalacia

Additional relevant MeSH terms:
Hypophosphatasia
Genetic Diseases, Inborn
Metabolic Diseases
Metabolism, Inborn Errors
Metal Metabolism, Inborn Errors

ClinicalTrials.gov processed this record on September 01, 2015