Phase 3 Study of ALXN1850 in Treatment-Naïve Pediatric Participants With HPP

Study Overview
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Brief Summary
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The primary purpose of this study is to evaluate the efficacy of ALXN1850 versus placebo on radiographic outcomes in pediatric participants with HPP who have not previously been treated with asfotase alfa.

Official Title
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A Phase 3, Randomized, Double-blinded, Placebo-controlled, Multicenter Study to Evaluate Efficacy and Safety of ALXN1850 Versus Placebo Administered Subcutaneously in Pediatric (2 to < 12 Years of Age) Participants With Hypophosphatasia Who Have Not Received Previous Treatment With Asfotase Alfa

Conditions
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Hypophosphatasia

Intervention / Treatment
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* Drug: ALXN1850
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of HPP documented in the medical records, and the following criteria fulfilled during the Screening Period without other probable cause than HPP: Presence of HPP-related rickets on skeletal X-rays, with a minimum Rickets Severity Score (RSS) of 1.0 AND Serum ALP activity below the age- and sex-adjusted normal range Must meet 1 of the following criteria: Documented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (Section 8.7) Plasma PLP above the upper limit of normal (ULN) during the Screening Period (central or local laboratory results allowed per local regulations) Tanner stage 2 or less during the Screening Period 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 ALXN1850 or the placebo comparator

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: ALXN1850<br>Starting at Day 1 of the Randomized Evaluation Period, the ALXN1850 group will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once every 2 weeks (q2w) via SC injection, for 24 weeks. Participants will enter the OLE Period and continue q2w dosing with ALXN1850 for up to 132 weeks. | Drug: ALXN1850<br>* Participants will receive a ALXN1850 via subcutaneous (SC) injection.<br>Drug: Placebo<br>* Participants will receive placebo via SC injection.<br>|
| Placebo Comparator: Placebo<br>Starting at Day 1 during the Randomized Evaluation Period, participants will receive placebo q2w for a total of 24 weeks. Participants will enter the OLE Period and continue q2w dosing with ALXN1850 for up to 132 weeks. | Drug: Placebo<br>* Participants will receive placebo via SC injection.<br>|

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) Score at the end of the Randomized Evaluation Period (Day 169) |  | Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| RGI-C Responder at the end of the Randomized Evaluation Period (Day 169) |  | Day 169 | 

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