Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa

Study Overview
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Brief Summary
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The primary purpose of this study is to assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa.

Official Title
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A Phase 3, Randomized, Open-label, Parallel-arm, Active-controlled, Multicenter Study to Evaluate Safety and Efficacy of ALXN1850 Versus Asfotase Alfa Administered Subcutaneously in Pediatric Participants (2 to < 12 Years of Age) With Hypophosphatasia (HPP) Previously Treated With Asfotase Alfa

Conditions
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Hypophosphatasia

Intervention / Treatment
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* Drug: ALXN1850
* Drug: asfotase alfa


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HPP documented in the medical records Presence of open growth plates by X-ray during Screening Period Tanner stage 2 or less during the Screening Period Must have been treated with 6 mg/kg/ week of asfotase alfa via SC injection administered as either 2mg/kg 3 times per week or 1 mg/kg 6 times per week for ≥ 6 months before Day 1 Exclusion Criteria: History or presence of cardiovascular, respiratory, hepatic, renal, gastrointestinal, endocrinological, hematological, neurological disorders, or any other disorders that are capable of significantly altering the absorption, metabolism, or elimination of drugs; constituting a risk when taking the study intervention; or interfering with the interpretation of data as determined by the Investigator. Diagnosis of primary or secondary hyperparathyroidism Hypoparathyroidism, unless secondary to HPP Any new fracture within 12 weeks before Day 1 (excluding pseudofractures) Planned surgical intervention which may impact the results of study assessments (in the opinion of the Investigator) during the Randomized Evaluation Period History of allergy or hypersensitivity to any ingredient contained in asfotase alfa or ALXN1850 Body weight < 10 kg during the Screening Period

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1850<br>Starting at Day 1 of the Randomized Evaluation Period participants will receive ALXN1850 for a total of 24 weeks. Participants will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection. During Part A of the OLE Period, participants will have frequent visits over the first 24 weeks; Part B of the OLE Period participants will have visits every 9 months for up to approximately 108 weeks. | Drug: ALXN1850<br>* ALXN1850 will be administered via subcutaneous (SC) injection.<br>Drug: asfotase alfa<br>* Asfotase alfa will be administered via SC injection.<br>|
| Experimental: asfotase alfa<br>Starting at Day 1 of the Randomized Evaluation Period, participants will receive asfotase alfa for a total of 24 weeks. Participants will receive 6 mg/kg/week of asfotase alfa via SC injection as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week. Part A of the OLE Period participants will have frequent visits over the first 24 weeks; Part B will have visits every 9 months for up to approximately 108 weeks. | Drug: asfotase alfa<br>* Asfotase alfa will be administered via SC injection.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Treatment-emergent Adverse Events (TEAEs) |  | Baseline Through Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Rickets Severity Score (RSS) at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in 6-Minute Walk Test (6MWT) at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Percent Predicted 6MWT at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Bruininks Oseretsky Test of Motor Proficiency, Second Edition (BOT2) Score at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Peabody Developmental Motor Scales, Third Edition (PDMS-3) Score at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypophosphatasia, HPP, Asfotase Alfa, ALXN1850