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

August 3, 2023 updated by: Alexion

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Phase 2

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

5 years to 12 years (Child)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Skeletal radiographs using a qualitative Clinical Global Impression of Change (CGI-C) scoring system
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
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
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Alexion

Investigators

  • Principal Investigator: Michael P. Whyte, MD, Shriners Hospital, St. Louis. MO

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2009

Primary Completion (Estimated)

December 1, 2014

Study Completion (Estimated)

December 1, 2014

Study Registration Dates

First Submitted

May 4, 2009

First Submitted That Met QC Criteria

May 5, 2009

First Posted (Estimated)

May 6, 2009

Study Record Updates

Last Update Posted (Actual)

August 4, 2023

Last Update Submitted That Met QC Criteria

August 3, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENB-004-09

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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