Phase 3 Study of ALXN1850 in Pediatric Participants With HPP Previously Treated With Asfotase Alfa (CHESTNUT)

A Phase 3, Randomized, Open-label, Parallel-arm, Active-controlled, Multicenter Study to Evaluate Safety and Efficacy of ALXN1850 Versus Asfotase Alfa Administered Subcutaneously in Pediatric Participants (2 to < 12 Years of Age) With Hypophosphatasia (HPP) Previously Treated With Asfotase Alfa

The primary purpose of this study is to assess the safety and tolerability of ALXN1850 versus asfotase alfa in pediatric participants with HPP previously treated with asfotase alfa.

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Mar del Plata, Argentina, B7600
    • Research Site
• Australia
  • South Brisbane, Australia, 4101
    • Research Site
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L1
      • Research Site
• Japan
  • Bunkyō City, Japan, 113-8431
    • Research Site
  • Minatoku, Japan, 105-8471
    • Research Site
  • Suita-shi, Japan, 565-0871
    • Research Site
  • Yonago-shi, Japan, 683-8504
    • Research Site
• Turkey (Türkiye)
  • Altındağ, Turkey (Türkiye), 06230
    • Research Site
  • Ankara, Turkey (Türkiye), 06560
    • Research Site
  • Edirne, Turkey (Türkiye), 22030
    • Research Site
  • Erzurum, Turkey (Türkiye), 25240
    • Research Site
  • Istanbul, Turkey (Türkiye), 34899
    • Research Site
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Research Site
  • Manchester, United Kingdom
    • Research Site
  • Sheffield, United Kingdom, S10 2TH
    • Research Site
• United States
  • Connecticut
    • Hartford, Connecticut, United States, 06106
      • Research Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Research Site
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • Research Site
  • Missouri
    • Kansas City, Missouri, United States, 64108
      • Research Site
  • North Carolina
    • Durham, North Carolina, United States, 27705
      • Research Site
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • 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
• Presence of open growth plates by X-ray during Screening Period
• Tanner stage 2 or less during the Screening Period
• Must have been treated with 6 mg/kg/ week of asfotase alfa via SC injection administered as either 2mg/kg 3 times per week or 1 mg/kg 6 times per week for ≥ 6 months before Day 1. Note: participants currently treated with 9 mg/kg (eg, 3 mg/kg 3 times per week) will not be allowed in the study.

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 asfotase alfa or ALXN1850
• Body weight < 10 kg during the Screening Period

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ALXN1850; Starting at Day 1 of the Randomized Evaluation Period participants will receive ALXN1850 for a total of 24 weeks. Participants will receive bodyweight dependent doses of either 20mg, 35mg or 50mg of ALXN1850 once q2w via SC injection. During Part A of the OLE Period, participants will have frequent visits over the first 24 weeks; Part B of the OLE Period participants will have visits every 9 months for up to approximately 108 weeks.	Drug: ALXN1850; ALXN1850 will be administered via subcutaneous (SC) injection.; Drug: asfotase alfa; Asfotase alfa will be administered via SC injection.
Experimental: asfotase alfa; Starting at Day 1 of the Randomized Evaluation Period, participants will receive asfotase alfa for a total of 24 weeks. Participants will receive 6 mg/kg/week of asfotase alfa via SC injection as either 2 mg/kg 3 times per week or 1 mg/kg 6 times per week. Part A of the OLE Period participants will have frequent visits over the first 24 weeks; Part B will have visits every 9 months for up to approximately 108 weeks.	Drug: asfotase alfa; Asfotase alfa will be administered via SC injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants with Treatment-emergent Adverse Events (TEAEs)	Baseline Through 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
Radiographic Global Impression of Change (RGI-C) Score at the end of the Randomized Evaluation Period (Day 169)	Baseline, Day 169

Collaborators and Investigators

• Sponsor: Alexion Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 2, 2024
• Primary Completion (Actual): July 23, 2025
• Study Completion (Estimated): February 29, 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 5, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Hypophosphatasia; HPP; Asfotase Alfa; 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; asfotase alfa
• Other Study ID Numbers: D8590C00004; ALXN1850-HPP-303 (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