Clinical trial NCT01419028: A Retrospective Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
Official title: A Retrospective, Non-interventional Epidemiologic Study of the Natural History of Patients With Severe Perinatal and Infantile Hypophosphatasia (HPP)
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Hypophosphatasia (HPP)
Keywords: Hypophosphatasia
HPP
Bone disease
Soft bones
Low alkaline phosphatase
Genetic metabolic disorder
Alkaline phosphatase
Tissue non-specific alkaline phosphatase
Rickets
Osteomalacia
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2011-08-17
Enrollment: 48
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
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.

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

Eligibility criteria: 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

Primary outcomes:
measure: Survival
timeFrame: Retrospective data collected on or before the data of abstraction.
Secondary outcomes:
measure: Invasive Ventilator-free Survival Time
timeFrame: Retrospective data collected on or before the date of abstraction.
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Indianapolis
country: United States
facility: Indiana University school of medicine
state: Indiana
city: Saint Louis
country: United States
facility: Shriners Hospital for Children
state: Missouri
city: Portland
country: United States
facility: Oregon Health & Science University
state: Oregon
city: Fort Worth
country: United States
facility: Cook Children's Health Care System
state: Texas
city: Parkville
country: Australia
facility: Royal Children's Hospital
city: Winnipeg
country: Canada
facility: University of Manitoba Health Sciences Centre
city: Mainz
country: Germany
facility: Universitatsmedizin Mainz, Villa
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg Kinderklinik, Pädiatrische Infektiologie und Immunologie
city: Madrid
country: Spain
facility: Hospital Infantil Universitario Nino Jesus Universidad autonoma de Madrid
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Birmingham
country: United Kingdom
facility: Birmingham Childrens Hospital
Study officials:
References:
citation: Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, Thompson DD, Bishop N, Hofmann C. Asfotase Alfa Treatment Improves Survival for Perinatal and Infantile Hypophosphatasia. J Clin Endocrinol Metab. 2016 Jan;101(1):334-42. doi: 10.1210/jc.2015-3462. Epub 2015 Nov 3.