A Prospective Sub-Study of the Global Hypophosphatasia Registry

Study Overview
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Brief Summary
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In this prospective observational sub-study, participants with pediatric-onset hypophosphatasia (HPP) (perinatal/infantile- or juvenile-onset) of any age will be followed for a minimum of 5 years at sites in the United States and potentially 1 or 2 other countries.

Official Title
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A Prospective Observational Sub-Study of the Global Hypophosphatasia Registry to Describe the Potential Risk of Immune-Mediated Loss of Pharmacological Effect of Asfotase Alfa in Participants With Hypophosphatasia

Conditions
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Hypophosphatasia

Intervention / Treatment
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* Biological: Asfotase Alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Any age or sex with a confirmed diagnosis of pediatric-onset HPP (that is, first HPP sign or symptom presented at < 18 years of age). Currently receiving asfotase alfa treatment at Enrollment (not treatment-naïve) or the Physician has decided to resume (not treatment-naïve) or start (treatment-naïve) the participant's asfotase alfa treatment within 6 months after Enrollment. Participant must have documented alkaline phosphatase (ALP) activity below the lower limit of normal for age and sex, and a documented ALPL gene mutation (Note: An exception is made for infants with clinical features of HPP plus low ALP who need to start asfotase alfa treatment right away, at the Physician's discretion, but do not yet have a genetic result. In this case, ALPL gene documentation is not required at the time of sub-study enrollment but should be documented within 6 months after Enrollment). Participant or participant's parent/legally authorized representative is able to read and/or understand the informed consent and study questionnaires in the local language. Participant or participant's parent/legally authorized representative must be willing and able to give signed informed consent for this sub-study, and the participant must be willing to give written informed assent, if appropriate and required by local regulations. Exclusion Criteria: Currently participating in an Alexion-sponsored interventional clinical study. Participants who have concluded participation in an Alexion-sponsored asfotase alfa clinical study are eligible to enroll in this sub-study.
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 |
| --- | --- |
| Participants with Pediatric-onset HPP<br>Each participant will be followed for a minimum of 5 years or, if applicable, until early withdrawal. Biochemical, clinical, imaging (if clinically indicated), and functional/quality of life outcomes relevant to HPP will be assessed. | Biological: Asfotase Alfa<br>* All participants will receive asfotase alfa subcutaneously per standard of care. Unless otherwise specified per the Physician's standard of care, participants aged < 2 years are recommended for a clinic visit approximately every 3 months after Enrollment until 2 years of age, after which they should have a clinic visit approximately every 6 months. Participants should be followed for 5 years, as possible.<br>* Other names: Strensiq;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence Of Immune-mediated Loss Of Effectiveness According To The Treating Physician | This will be based on clinical and biochemical assessments as well as positive anti-drug antibodies and positive neutralizing antibodies. | Up to 5 years | 
| Occurrence Of Immune-mediated Serious Adverse Events | These serious adverse events will include serious hypersensitivity reactions and anaphylaxis. | Up to 5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pediatric Onset, HPP, Asfotase alfa