Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Hypophosphatasia

Study Overview
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Brief Summary
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Hypophosphatasia is a rare inherited metabolic disorder due to inactivating mutations of the ALPL-Gene. Particularly among adult patients, clinical manifestation exhibits a broad range of signs and symptoms, most commonly associated with musculoskeletal disabilities and compromised quality of life. Enzyme replacement therapy with Asfotase alfa (AA) is available and approved for patients with pediatric onset of the disease. This single-center observational cohort study aims at collecting clinical routine data regarding the course treatment, quality of life and physical performance in patients treated with Asfotase alfa in line with the label for pediatric-onset hypophosphatasia.

Official Title
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An Observational, Longitudinal Study to Evaluate and Monitor Physical Performance of Adults Treated With Asfotase Alfa for Pediatric-Onset Hypophosphatasia

Conditions
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Hypophosphatasia

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years at the time of enrollment Clinical diagnosis of pediatric-onset HPP based on low ALP (age- and sex-adjusted) and/or genetic confirmation of ALPL mutation(s), and clinical symptoms consistent with HPP Participant currently receiving commercial asfotase alfa treatment for HPP at the Orthopedic Institute of the Julius-Maximilians-University Würzburg, as per standard of care Willingness to participate in the study Signed informed consent Exclusion Criteria: Unwillingness / anticipated inability to attend further visits Off-label treatment with asfotase alfa Current participation in an Alexion Sponsored Trial Experimental drug/treatment

Ages Eligible for Study
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Minimum Age: 18 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Pediatric-onset Hypophosphatasia<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Physical Performance | 6 Minute Walk Test [meters] | 1 year of treatment compared to pre-treatment baseline | 
| Physical Performance | Short Physical Performance Battery [points] | 1 year of treatment compared to pre-treatment baseline | 
| Physical Performance | Timed Up and Go Test [seconds] | 1 year of treatment compared to pre-treatment baseline | 
| Physical Performance | Handheld dynamometry [kilogram] | 1 year of treatment compared to pre-treatment baseline | 
| Physical Performance | Jumping mechanography [W/kg bodyweight] | 1 year of treatment compared to pre-treatment baseline | 
| Physical Performance | Use of assistive devices descriptive measure | 1 year of treatment compared to pre-treatment baseline | 
| Body composition | Bioelectrical Impedance Analysis [proportional mass of muscle, water and fat in kg] | 1 year of treatment compared to pre-treatment baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Health related quality of life | Questionnaire | 1 year of treatment compared to pre-treatment baseline | 
| Bone Mineral Density | Dual x-ray absorptiometry (DXA) | 1 year of treatment compared to pre-treatment baseline | 
| Skeletal pathology | Descriptive assessment of available imaging (x-Ray, CT, MRI, histological sections) | 1 year of treatment compared to pre-treatment baseline | 
| Laboratory evaluation | Parathyroid hormone [PTH, pg/ml] | 1 year of treatment compared to pre-treatment baseline | 
| Laboratory evaluation | Serum-Calcium [mmol/l] | 1 year of treatment compared to pre-treatment baseline | 
| Laboratory evaluation | Serum-Phosphorus [mmol/l] | 1 year of treatment compared to pre-treatment baseline | 
| Laboratory evaluation | Serum-Creatinine [µmol/l], incl. calculated eGFR | 1 year of treatment compared to pre-treatment baseline | 
| Laboratory evaluation | Fibroblast Growth Factor 23 / FGF-23 [RU/ml] | 1 year of treatment compared to pre-treatment baseline | 
| Safety assessment | Injection site reactions (descriptive) | 1 year of treatment compared to pre-treatment baseline | 
| Safety assessment | Injection associated reactions (descriptive) | 1 year of treatment compared to pre-treatment baseline | 
| Safety assessment | Ectopic calcifications (descriptive) | 1 year of treatment compared to pre-treatment baseline | 
| Safety assessment | Adverse events (descriptive) | 1 year of treatment compared to pre-treatment baseline |