Retrospective, Non-interventional Natural History of Patients With Juvenile-onset Hypophosphatasia (HPP)

Study Overview
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Brief Summary
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The purpose of this study is to characterize the natural history of HPP in patients with Juvenile-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 Juvenile-onset Hypophosphatasia (HPP)

Conditions
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Hypophosphatasia (HPP)

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Documented informed consent unless patient is deceased Patients with Juvenile-onset HPP, defined as documented onset of first signs/symptoms at ≥ 6 months to ˂18 years Documented diagnosis of HPP as indicated by skeletal manifestations and low alkaline phosphatase or genotyping Exclusion Criteria: Received treatment with asfotase alfa in the ENB-006-09 study and/or currently enrolled in the ENB-008-10 study Received other treatment and/or intervention to treat HPP up to 15 years old Other clinically significant disease

Ages Eligible for Study
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Minimum Age: 5 Years

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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Global Impression of Change - RGI-C | The RGI-C scale is a 7-point ordinal scale that is used to evaluate musculoskeletal characteristics of HPP (eg, metaphyseal fraying, demineralization of distal metaphyses). The scores range from -3 (severe worsening) to +3 (complete or near-complete healing). | Between Baseline (earliest available, complete, and readable x-ray set) and all available, readable post-Baseline x-ray sets during the period of patients' aged 5 to 15 years, inclusive. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Height Z-score From Baseline to Last Assessment | Height measurements were assigned to Z-scores which were calculated using the Centers for Disease Control and Prevention (CDC) 2000 growth charts and methodology. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome. | Any available growth data during the period of patients' aged 5 to 15 years, inclusive. Baseline is the earliest available assessment while post baselines are time points after Baseline during the defined age period. | 
| Change in Weight Z-score From Baseline to Last Assessment | Weight measurements were assigned a Z-score which was calculated using the Centers for Disease Control and Prevention (CDC) 2000 growth charts and methodology. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z-scores indicate a better outcome. | Any available growth data during the period of patients' aged 5 to 15 years, inclusive. Baseline is the earliest available assessment while Post baselines are time points after Baseline during the defined age period. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypophosphatasia, HPP, bone disease, Soft Bones, low Alkaline Phosphatase, genetic metabolic disorder, alkaline phosphatase, tissue non-specific alkaline phosphatase, rickets, osteomalacia