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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Hypophosphatasia
• Intervention / Treatment: Drug: ALXN1850; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Nedlands, Australia, 6009
    • Research Site
  • Parkville, Australia, 3052
    • Research Site
• Belgium
  • Brussels, Belgium, 1020
    • Research Site
• Brazil
  • Brasília, Brazil, 71625-009
    • Research Site
  • Porto Alegre, Brazil, 90610-261
    • Research Site
  • Recife, Brazil, 50740-465
    • Research Site
  • Salvador, Brazil, 40050-410
    • Research Site
  • São Paulo, Brazil, 05403-900
    • Research Site
  • São Paulo, Brazil, 01409-902
    • Research Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2E 7H7
      • Research Site
  • Manitoba
    • Winnepeg, Manitoba, Canada, R3E 3P4
      • Research Site
• China
  • Beijing, China, 100045
    • Research Site
  • Guangzhou, China, 510623
    • Research Site
  • Shanghai, China, 2000127
    • Research Site
  • Shenzhen, China, 518053
    • Research Site
• Finland
  • Helsinki, Finland, 00290
    • Research Site
• Israel
  • Ashkelon, Israel, 7830604
    • Research Site
• Mexico
  • Chihuahua City, Mexico, 31238
    • Research Site
• Poland
  • Lodz, Poland, 93-338
    • Research Site
• Romania
  • Bucharest, Romania, 011863
    • Research Site
• Spain
  • Madrid, Spain, 28046
    • Research Site
  • Vitoria-Gasteiz, Spain, 01009
    • Research Site
• Sweden
  • Stockholm, Sweden, 17176
    • Research Site
• Taiwan
  • Taipei, Taiwan, 100
    • Research Site
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06560
    • Research Site
  • Bursa, Turkey (Türkiye), 16059
    • Research Site
  • Erzurum, Turkey (Türkiye), 25240
    • Research Site
  • Istanbul, Turkey (Türkiye), 34899
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Research Site
• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1850; 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; Participants will receive a ALXN1850 via subcutaneous (SC) injection.; Drug: Placebo; Participants will receive placebo via SC injection.
Placebo Comparator: Placebo; 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; Participants will receive placebo via SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2024
• Primary Completion (Actual): January 6, 2026
• Study Completion (Estimated): August 24, 2028

Study Registration Dates

• First Submitted: October 6, 2023
• First Submitted That Met QC Criteria: October 6, 2023
• First Posted (Actual): October 12, 2023

Study Record Updates

• Last Update Posted (Actual): May 28, 2026
• Last Update Submitted That Met QC Criteria: May 26, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hypophosphatasia; HPP; ALXN1850
• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Metal Metabolism, Inborn Errors; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Hypophosphatasia; Substandard Drugs; Pharmaceutical Preparations; Counterfeit Drugs
• Other Study ID Numbers: D8590C00003; ALXN1850-HPP-305 (Other Identifier: Alexion Pharmaceuticals, Inc.)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Alexion has a public commitment to allow requests for access to study data and will be supplying a protocol, CSR, and plain language summaries.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No