Hypophosphatasia
Conditions
Keywords
Hypophosphatasia, HPP, Asfotase Alfa, ALXN1850
Brief summary
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.
Interventions
DRUGALXN1850
ALXN1850 will be administered via subcutaneous (SC) injection.
DRUGPlacebo
Placebo will be administered via SC injection.
Sponsors
Alexion Pharmaceuticals, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
* Diagnosis of HPP documented in the medical records * Must meet 1 of the following criteria: 1. Documented ALPL gene variant (pathogenic, likely pathogenic, or variant of unknown significance) from a Clinical Laboratory Improvement Amendments (CLIA) or ISO 15189 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) * Must meet 1 of the following criteria without a probably cause other than HPP: 1. Serum ALP activity below the age- and sex-adjusted normal range during the screening period as measured by the Central Laboratory 2. Two 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 CLIA or ISO 15189 certified, or have other local equivalent laboratory certification with Alexion's approval. * 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)
Design outcomes
Primary
| Measure | 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
| Measure | 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 BPI-SF pain severity score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only) | Baseline, Day 169 |
| Change from Baseline in FACIT-Fatigue score at the end of the Randomized Evaluation Period (Day 169) (adult cohort only) | 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 |
Countries
Argentina, Australia, Brazil, Canada, China, France, Germany, Israel, Italy, Japan, Poland, South Korea, Spain, Taiwan, Turkey (Türkiye), United Kingdom, United States
Outcome results
None listed