Phase 3 Study of ALXN1850 Versus Placebo in Adolescent and Adult Participants With HPP Who Have Not Previously Been Treated With Asfotase Alfa

Study Overview
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Brief Summary
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The primary objective of this study is to assess the efficacy of ALXN1850 versus placebo on functional outcomes in adolescent and adult 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 (Recombinant Alkaline Phosphatase) Administered Subcutaneously in Adolescent (12 to < 18 Years of Age) and Adult Participants With Hypophosphatasia Who Have Not Previously Been Treated 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 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) Serum ALP activity below the age- and sex-adjusted normal range during the screening period, without a probable cause other than HPP Two separate 6MWTs at below 85% of the predicted distance (for age, sex, weight, and height) during the Screening Period without a probable cause other than HPP 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 (Table 9)

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 130 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 |
| --- | --- |
| Placebo Comparator: Placebo Group<br>During the Randomized Evaluation Period, the placebo group will receive placebo on Day 1, followed by once every 2 weeks (q2w) via SC injection for 24 weeks. Participants will enter the OLE Period and receive bodyweight dependent doses of either 20mg, 35mg, or 50mg of ALXN1850 and continue q2w dosing with ALXN1850 for up to 132 weeks. | Drug: Placebo<br>* Placebo will be administered via SC injection.<br>|
| Experimental: ALXN1850 Group<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 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>* ALXN1850 will be administered via subcutaneous (SC) injection.<br>Drug: Placebo<br>* Placebo 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 |
| --- | --- | --- |
| Change from Baseline in 6-Minute Walk Test (6MWT) at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in 30-second Sit to Stand (STS) Test Score at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Lower Extremity Functional Scale (LEFS) Score at the end of the Randomized Evaluation Period (Day 169) |  | Baseline, Day 169 | 
| Change from Baseline in Timed Up-and-Go (TUG) 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 | 
| Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169) |  | Day 169 | 
| RGI-C Responder at the end of the Randomized Evaluation Period (Day 169) |  | Day 169 | 
| Change from Baseline in Rickets Severity Score (RSS) 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