A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)

March 28, 2019 updated by: Alexion Pharmaceuticals

A Retrospective, Non-interventional Epidemiologic Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)

This study aims to characterize the natural history of patients with severe perinatal or infantile onset HPP.

Study Overview

Status

Completed

Conditions

Detailed Description

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.

Study Type

Observational

Enrollment (Actual)

48

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Australia
      • Parkville, Australia
        • Royal Children's Hospital
  • Canada
      • Winnipeg, Canada, MB R3A 1R9
        • University of Manitoba Health Sciences Centre
  • Germany
      • Mainz, Germany, 55131
        • Universitatsmedizin Mainz, Villa
      • Würzburg, Germany, 97080
        • Universitätsklinikum Würzburg Kinderklinik, Pädiatrische Infektiologie und Immunologie
  • Spain
      • Madrid, Spain
        • Hospital Infantil Universitario Nino Jesus Universidad autonoma de Madrid
  • Taiwan
      • Taipei, Taiwan, 10041
        • National Taiwan University Hospital
  • United Kingdom
      • Birmingham, United Kingdom
        • Birmingham Childrens Hospital
  • United States
    • California
      • Los Angeles, California, United States
        • Cedars-Sinai Medical Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University School of Medicine
    • Missouri
      • Saint Louis, Missouri, United States
        • Shriners Hospital for Children
    • Oregon
      • Portland, Oregon, United States
        • Oregon Health & Science University
    • Texas
      • Fort Worth, Texas, United States
        • Cook Children's Health Care System

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Patients with perinatal and/or infantile onset HPP. Thirty-six patients were invasively ventilated or died, and 12 patients were censored.

Description

Inclusion Criteria:

  • Parent(s) or legal guardian(s) must provide written informed consent prior to data abstraction, unless all of the following apply:
  • The patient is deceased; AND
  • The responsible IRB/IEC/REB does not require informed consent per a review of their documented local policies for collecting retrospective data on patients who are deceased; AND
  • Written confirmation is received from the responsible IRB/IEC/REB confirming that the abstracted data can be analyzed and used to support regulatory filings by the Sponsor
  • Patient must have a documented diagnosis of HPP as indicated by 1 or more of the following:
  • Documented ALPL gene mutation(s)
  • Serum alkaline phosphatase (ALP) below the age-adjusted normal range and either plasma pyridoxal 5'-phosphate (PLP) or urinary phosphoethanolamine (PEA) above the upper limit of normal
  • Serum ALP below the age-adjusted normal range and HPP-related radiographic abnormalities on X-ray
  • Patient must have onset of signs of HPP prior to 6 months of age and have documentation of 1 or more of the following characteristics of perinatal and infantile HPP:
  • Respiratory compromise (up to and including respiratory failure) requiring institution of respiratory support measure(s), requiring medication(s) for management of symptom(s), and/or associated with other respiratory complications (e.g., pneumonia(s), respiratory tract infection(s))
  • Pyridoxine (vitamin B6)-responsive seizures
  • Rachitic chest deformity

Exclusion Criteria:

Patients will be excluded from study participation if they have 1 or more of the following exclusion criteria:

  • Patient received treatment with asfotase alfa at any time prior to data abstraction
  • Patient has clinically significant other disease

Both living and deceased patients will be considered for study participation

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

  • Observational Models: Cohort
  • Time Perspectives: Retrospective

Cohorts and Interventions

Group / Cohort
Patients with perinatal and/or infantile onset HPP
Patients with a confirmed diagnosis of perinatal or infantile onset hypophosphatasia (HPP)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Survival
Time Frame: Retrospective data collected on or before the data of abstraction.
Overall survival is defined as the time from birth to time of death.
Retrospective data collected on or before the data of abstraction.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Invasive Ventilator-free Survival Time
Time Frame: Retrospective data collected on or before the date of abstraction.
Invasive ventilator-free survival is defined as the time during which the patient is alive and not invasively ventilated. For the purpose of this study, invasive ventilation is defined as mechanical ventilation via intubation of trachaeostomy.
Retrospective data collected on or before the date of abstraction.

Collaborators and Investigators

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

Sponsor

Alexion Pharmaceuticals

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

Helpful Links

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

August 1, 2012

Primary Completion (Actual)

June 1, 2013

Study Completion (Actual)

February 1, 2014

Study Registration Dates

First Submitted

August 16, 2011

First Submitted That Met QC Criteria

August 16, 2011

First Posted (Estimate)

August 17, 2011

Study Record Updates

Last Update Posted (Actual)

April 1, 2019

Last Update Submitted That Met QC Criteria

March 28, 2019

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ENB-011-10

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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