Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta

NCT ID: NCT05768854

Last Updated: 2025-12-02

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE3
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-14
• Study Completion Date: 2027-04-30

Brief Summary

The primary objective of the study is to evaluate the effect of setrusumab vs intravenous bisphosphonates (IV-BP) on reduction in fracture rate, including morphometric vertebral fractures in pediatric participants.

Detailed Description

Participants will be randomized 1:1 to receive either setrusumab or IV-BP. Following randomization, participants will receive setrusumab or IV-BP for up to 24 months during the Active-controlled Period. At the end of the Active-controlled Period all participants will enter the Extension Period and participants assigned to IV-BP will transition to setrusumab. During the Extension Period, all participants will receive setrusumab for a minimum of 12 months or until setrusumab becomes commercially available in their respective country or the study is discontinued. The use of any bisphosphonate is prohibited throughout the Extension Period.

Conditions

Osteogenesis Imperfecta

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Intravenous Bisphosphonates (IV-BP) -> Setrusumab

Participants on IV-BP will continue their existing dose/regimen per investigator discretion; for participants not on IV-BP, the dose/regimen will be determined by the investigator.

After the active-controlled period, participants will receive Setrusumab during the extension period

Group Type: ACTIVE_COMPARATOR

Bisphosphonate

Intervention Type: DRUG

Administered per investigator discretion via intravenous (IV) infusion

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Setrusumab

Participants will receive Setrusumab during the active-controlled and extension period

Group Type: EXPERIMENTAL

Setrusumab

Intervention Type: BIOLOGICAL

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Interventions

Bisphosphonate

Administered per investigator discretion via intravenous (IV) infusion

Intervention Type: DRUG

Setrusumab

A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion

Intervention Type: BIOLOGICAL

Other Intervention Names

BPS804; UX143

Eligibility Criteria

Inclusion Criteria

• Male or female 2 to < 7 years of age at time of informed consent
• Clinical diagnosis of OI Types I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2
• History of ≥ 1 fracture in the past 12 months, ≥ 2 fractures in the past 24 months, or ≥ 1 femur, tibia, or humerus fracture in the past 24 months
• Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI
• Serum 25-hydroxyvitamin D level ≥ 20 ng/mL at the Screening visit. If 25-hydroxyvitamin D levels are below 20 ng/mL, the subject may be rescreened after a minimum of 14 days of vitamin D supplementation as directed by the Investigator

Exclusion Criteria

• Contraindication for the use of IV bisphosphonates based on clinical judgment of the Investigator
• History of skeletal malignancies or bone metastases at any time
• History of neural foraminal stenosis (except if due to scoliosis)
• Clinical manifestations of Chiari malformation or basilar invagination. Presence of any other neurologic disease that has been clinically unstable within past 2 years requires review by the Medical Monitor.
• History of or current uncontrolled concomitant diseases that may impact bone metabolism, such as hypo/hyperparathyroidism, abnormal thyroid function, nephrotic syndrome, or Stage IV/V renal disease
• Any skeletal condition (other than OI) leading to bone deformity and/or increased risk of fractures, such as rickets, osteopetrosis, idiopathic juvenile osteoporosis, or skeletal dysplasia
• History of known cardiovascular disease such as coronary artery anomaly, Kawasaki disease, myocarditis, cardiomyopathy, myocardial infarction, stroke, or thromboembolic disease. Individuals with other congenital or acquired cardiovascular disease necessitating echocardiogram require Medical Monitor review. Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with cardiovascular risk factors such as confirmed arterial hypertension.
• Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limit reference ranges after a recommended ≥ 4 hour fast, at Screening
• Estimated glomerular filtration rate <=35 mL/min/1.73 m2 at Screening
• Prior treatment with growth hormone, denosumab, anti-sclerostin antibody, or other anabolic or anti-resorptive medications impacting the bone (other than bisphosphonates) at any time
• History of external radiation therapy
• Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects
• Presence or history of any condition that, in the view of the Investigator, would interfere with participation, pose undue risk, or would confound interpretation of results
• Use of any investigational product or investigational medical device within 4 weeks or 5 half-lives (whichever is longer) of investigational drug prior to Screening, or during the study (per discretion of the Investigator in consultation with the Medical Monitor)
• Concurrent participation in another clinical study without prior approval from the study Medical Monitor

• Minimum Eligible Age: 2 Years
• Maximum Eligible Age: 6 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ultragenyx Pharmaceutical Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Director

Role: STUDY_DIRECTOR

Ultragenyx Pharmaceutical Inc

Locations

Phoenix Children's Hospital

Phoenix, Arizona, United States

Childrens Hospital LA

Los Angeles, California, United States

Children's Hospital Colorado

Aurora, Colorado, United States

Yale New Haven Hospital

New Haven, Connecticut, United States

Nemours/ Alfred i. duPoint Hospital for Children

Wilmington, Delaware, United States

Children's National Hospital DC

Washington D.C., District of Columbia, United States

University of South Florida

Tampa, Florida, United States

Shriners Hospitals for Children Chicago

Chicago, Illinois, United States

Washington University School of Medicine

St Louis, Missouri, United States

University of North Carolina at Chapel Hill (UNC)

Chapel Hill, North Carolina, United States

Vanderbilt University Medical Center (VUMC)

Nashville, Tennessee, United States

Cook Children's Medical Center

Fort Worth, Texas, United States

Baylor College of Medicine

Houston, Texas, United States

Hospital de Clinicas de Porto Alegre (HCPA)

Porto Alegre, Rio Grande do Sul, Brazil

Children's Hospital at London Health Sciences Centre

London, Ontario, Canada

Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa

Ottawa, , Canada

Institut Imagine

Paris, , France

Azienda Ospedaliera Universitaria Policlinico Umberto I

Roma, , Italy

Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis

Utrecht, , Netherlands

Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych

Lodz, , Poland

Countries

United States; Brazil; Canada; France; Italy; Netherlands; Poland

Related Links

https://www.ultraclinicaltrials.com/OI

Ultragenyx Osteogenesis Imperfecta (OI) Research Study

https://www.ultragenyx.com/our-research/our-clinical-trial-transparency-commitment/

Ultragenyx Transparency Commitment

Other Identifiers

UX143-CL314

Identifier Type: -

Identifier Source: org_study_id

2023-504196-24-00

Identifier Type: OTHER

Identifier Source: secondary_id