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

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

Detailed Description
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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.

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

Conditions
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Hypophosphatasia (HPP)

Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients with perinatal and/or infantile onset HPP<br>Patients with a confirmed diagnosis of perinatal or infantile onset hypophosphatasia (HPP) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Survival | 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 | 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. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rickets, Hypophosphatasia, HPP, Bone disease, Soft bones, Low alkaline phosphatase, Genetic metabolic disorder, Alkaline phosphatase, Tissue non-specific alkaline phosphatase, Osteomalacia