Hypophosphatasia
Conditions
Keywords
Hypophosphatasia, HPP, ALXN1850
Brief summary
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.
Interventions
DRUGALXN1850
Participants will receive a ALXN1850 via subcutaneous (SC) injection.
DRUGPlacebo
Participants will receive placebo via SC injection.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
double-blinded
Eligibility
Sex/Gender
ALL
Age
2 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of HPP documented in the medical records, and the following criteria fulfilled without other probable cause than HPP: 1. Presence of HPP-related rickets on skeletal X-rays during the Screening Period, with a minimum Rickets Severity Score (RSS) of 1.0 AND 2. Serum ALP activity below the age- and sex-adjusted normal range during the Screening Period as measured by the Central Laboratory OR 2 documented serum ALP activity results, at least 15 days apart, below the age- and sex-adjusted local laboratory normal range during the 24 months before the Day 1 Visit. Note: Local laboratories need to be Clinical Laboratory Improvement Amendments (CLIA) or ISO 15189 certified, or have other local equivalent laboratory certification with Alexion's approval. * Must meet 1 of the following criteria: 1. Documented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a CLIA certified laboratory (Section 8.7) 2. 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169) | Day 169 |
Secondary
| Measure | 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 |
Countries
Australia, Belgium, Brazil, Canada, China, Finland, Israel, Mexico, Poland, Romania, Spain, Sweden, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed