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

Alexion Pharmaceuticals

Status and phase: Active, not recruiting; Phase 3

Conditions: Hypophosphatasia

Treatments: Drug: Placebo; Drug: ALXN1850

Study type: Interventional

Funder types: Industry

Identifiers

NCT06079359

D8590C00003

ALXN1850-HPP-305 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 30 patients

Sex: All

Ages: 2 to 11 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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30 participants in 2 patient groups, including a placebo group

ALXN1850

Experimental group

Description:

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.

Treatment:

Drug: ALXN1850

Drug: Placebo

Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo