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

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.
ClinicalTrials.gov Identifier: NCT01419028
Recruitment Status : Completed
First Posted : August 17, 2011
Results First Posted : July 21, 2014
Last Update Posted : April 1, 2019
Information provided by (Responsible Party):
Alexion Pharmaceuticals

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

Condition or disease
Hypophosphatasia (HPP)

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.

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Study Type : Observational
Actual Enrollment : 48 participants
Observational Model: Cohort
Time Perspective: Retrospective
Official Title: A Retrospective, Non-interventional Epidemiologic Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
Study Start Date : August 2012
Actual Primary Completion Date : June 2013
Actual Study Completion Date : February 2014

Resource links provided by the National Library of Medicine

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

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01419028

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United States, California
Cedars-Sinai Medical Center
Los Angeles, California, United States
United States, Indiana
Indiana University school of medicine
Indianapolis, Indiana, United States, 46202
United States, Missouri
Shriners Hospital for Children
Saint Louis, Missouri, United States
United States, Oregon
Oregon Health & Science University
Portland, Oregon, United States
United States, Texas
Cook Children's Health Care System
Fort Worth, Texas, United States
Royal Children's Hospital
Parkville, Australia
University of Manitoba Health Sciences Centre
Winnipeg, Canada, MB R3A 1R9
Universitatsmedizin Mainz, Villa
Mainz, Germany, 55131
Universitätsklinikum Würzburg Kinderklinik, Pädiatrische Infektiologie und Immunologie
Würzburg, Germany, 97080
Hospital Infantil Universitario Nino Jesus Universidad autonoma de Madrid
Madrid, Spain
National Taiwan University Hospital
Taipei, Taiwan, 10041
United Kingdom
Birmingham Childrens Hospital
Birmingham, United Kingdom
Sponsors and Collaborators
Alexion Pharmaceuticals
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alexion Pharmaceuticals
ClinicalTrials.gov Identifier: NCT01419028    
Other Study ID Numbers: ENB-011-10
First Posted: August 17, 2011    Key Record Dates
Results First Posted: July 21, 2014
Last Update Posted: April 1, 2019
Last Verified: March 2019
Keywords provided by Alexion Pharmaceuticals:
Bone disease
Soft bones
Low alkaline phosphatase
Genetic metabolic disorder
Alkaline phosphatase
Tissue non-specific alkaline phosphatase
Additional relevant MeSH terms:
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Metal Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases