Safety and Efficacy Study of ENB-0040 in Juvenile Patients With Hypophosphatasia (HPP)

This study has been withdrawn prior to enrollment.
(Withdrawn pending further review of clinical design.)
Sponsor:
Information provided by (Responsible Party):
Alexion Pharma International Sarl
ClinicalTrials.gov Identifier:
NCT00894075
First received: May 4, 2009
Last updated: January 24, 2013
Last verified: April 2012
  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 of the study drug called ENB-0040 and see what effects is has on human juveniles and HPP.


Condition Intervention Phase
Hypophosphatasia
Biological: ENB-0040
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Single-Center, Case-Control Study of Safety, Efficacy and Pharmacokinetics of ENB-0040 (Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein) for Treatment of Hypophosphatasia in Children

Resource links provided by NLM:


Further study details as provided by Alexion Pharma International Sarl:

Primary Outcome Measures:
  • Skeletal radiographs using a qualitative Clinical Global Impression of Change (CGI-C) scoring system [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • PK using serum peak and trough levels and PD of plasma inorganic pyrophosphate (PPi) and plasma pyridoxal-5' phosphate (PLP) as biomarkers for HPP. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Enrollment: 0
Study Start Date: July 2009
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Intervention Details:
    Biological: ENB-0040
    1mg/kg subcutaneous injection thrice weekly for 6 months
    Other Names:
    • Human Recombinant Tissue Nonspecific Alkaline Phosphatase Fusion Protein
    • sALP-Fc-D10
Detailed Description:

Hypophosphatasia (HPP) is a rare inherited form of rickets and osteomalacia caused by inactivating mutations in the gene encoding the tissue-nonspecific isoenzyme of alkaline phosphatase (TNSALP). The prevalence of the disease is thought to be about 1:100,000 although it is markedly higher in a small Canadian Mennonite population (Fraser 1957, Chodirker 1990). Inheritance can be autosomal recessive or dominant, and penetrance is variable resulting in a wide range of clinical expressivity. HPP differs from other forms of rickets and osteomalacia in that serum levels of calcium and phosphorus are generally normal or even elevated (Whyte 2002). Low circulating levels of alkaline phosphatase with elevated serum or urine levels of the TNSALP substrates inorganic pyrophosphate (PPi), pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA) are the biochemical hallmarks of this inborn error of metabolism.

Disease severity in HPP is inversely related to the age at symptom presentation. The most severe cases occur in utero and almost invariably result in death, generally due to pulmonary compromise. Infants who present in the first six months of life have about 50% mortality. Children and adults have less severe disease but can have frequent fractures, bone pain, bowing of the long bones and muscle weakness, and morbidity is generally cumulative. Some patients cannot ambulate independently and end up wheelchair-bound.

  Eligibility

Ages Eligible for Study:   5 Years to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent from parent or legal guardian prior to participation
  2. Boys >/= 5 and < 12 years of age and girls >/= 5 and < 10 years of age with open growth plates at time of enrollment
  3. Documented history of HPP, as evidenced by:

    1. Presence of HPP-related rickets on skeletal radiographs
    2. Serum alkaline phosphatase (ALP) below age-adjusted normal range
    3. Plasma PLP at least twice the upper limit of normal (>/=220 nM)
  4. Ambulatory without the use of assistive devices
  5. Ability of patient and parent/guardian to comply with study requirements

Exclusion Criteria:

  1. Serum calcium or phosphorus below age-adjusted normal range
  2. History of sensitivity to any study drug constituent
  3. Medical condition, serious intercurrent illness, or other extenuating circumstance that, in the opinion of the investigator, may significantly interfere with study compliance, including all prescribed evaluations and follow-up activities
  4. Treatment with an investigational drug within 1 month before start of study drug
  5. Current enrollment in any other study involving an investigational new drug, device, or treatment for HPP (eg, bone marrow transplantation)
  6. Current evidence of a treatable form of rickets
  7. Prior treatment with bisphosphonates
  8. Bone fracture or orthopedic surgery within the past 12 months
  9. Major congenital abnormality other than those associated with HPP
  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: NCT00894075

Sponsors and Collaborators
Alexion Pharma International Sarl
Investigators
Principal Investigator: Michael P. Whyte, MD Shriners Hospital, St. Louis. MO
  More Information

Additional Information:
Publications:
Responsible Party: Alexion Pharma International Sarl
ClinicalTrials.gov Identifier: NCT00894075     History of Changes
Other Study ID Numbers: ENB-004-09
Study First Received: May 4, 2009
Last Updated: January 24, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Alexion Pharma International Sarl:
genetic metabolic disorder
alkaline phosphatase
tissue non-specific alkaline phosphatase
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 October 30, 2014