Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta (Cosmic)

An Open-label, Randomized, Active-Controlled, Phase 3 Study of Setrusumab Compared With Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta Types I, III or IV

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Osteogenesis Imperfecta
• Intervention / Treatment: Biological: Setrusumab; Drug: Bisphosphonate

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.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Rio Grande do Sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90035-903
      • Hospital de Clínicas de Porto Alegre (HCPA)
• Canada
  • Ottawa, Canada, KIH 8L1
    • Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa
  • Ontario
    • London, Ontario, Canada, N6A 5W9
      • Children's Hospital at London Health Sciences Centre
• France
  • Paris, France, 75015
    • Institut Imagine
• Italy
  • Roma, Italy, 00161
    • Azienda Ospedaliera Universitaria Policlinico Umberto I
• Netherlands
  • Utrecht, Netherlands, 3584 EA
    • Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis
• Poland
  • Lodz, Poland, 91-738
    • Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85206
      • Phoenix Children's Hospital
  • California
    • Los Angeles, California, United States, 90027
      • Childrens Hospital LA
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Connecticut
    • New Haven, Connecticut, United States, 06510
      • Yale New Haven Hospital
  • Delaware
    • Wilmington, Delaware, United States, 19803
      • Nemours/ Alfred i. duPoint Hospital for Children
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20010
      • Children's National Hospital DC
  • Florida
    • Tampa, Florida, United States, 33612
      • University of South Florida
  • Illinois
    • Chicago, Illinois, United States, 60707
      • Shriners Hospitals for Children Chicago
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Washington University School of Medicine
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill (UNC)
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center (VUMC)
  • Texas
    • Fort Worth, Texas, United States, 76104
      • Cook Children's Medical Center
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 years to 4 years (Child)
• Accepts Healthy Volunteers: No

Description

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

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
Active Comparator: 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	Biological: Setrusumab; A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion; Other Names: BPS804; UX143; Drug: Bisphosphonate; Administered per investigator discretion via intravenous (IV) infusion
Experimental: Setrusumab; Participants will receive Setrusumab during the active-controlled and extension period	Biological: Setrusumab; A fully human sclerostin neutralizing monoclonal antibody (mAb) administered once a month (QM) via intravenous (IV) infusion; Other Names: BPS804; UX143

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Annualized Rate of All Radiographically-Confirmed Fractures, Including Morphometric Vertebral Fractures, at the Primary Analysis	Up to 24 Months

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Setrusumab Concentration	Up to 24 Months
Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)	Up to 24 Months
Percent Change from Baseline in DXA BMD at the Lumbar Spine at the Primary Analysis	Up to 24 Months
Number of Participants With Anti-Setrusumab Binding and Neutralizing Antibodies	Up to 24 Months
Annualized Rate of Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, but Including Fractures of the Fingers, Toes, Face and Skull at the Primary Analysis	Up to 24 Months
Annualized Rate of All Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures, and Fractures of the Fingers, Toes, Face and Skull, at the Primary Analysis	Up to 24 Months
Change from Baseline in Dual-energy X-ray Absorptiometry (DXA) Bone Mineral Density (BMD) Z-score at the Lumbar Spine at the Primary Analysis	Up to 24 Months
Proportion of Participants Experiencing New Radiographically-Confirmed Fractures, including Morphometric Vertebral Fractures, at the Primary Analysis	Up to 24 Months
Change from Baseline in Pediatric Orthopedic Society of North America Pediatric Outcomes Data Collection Instrument (POSNA-PODCI) Sports/Physical Functioning and Pain/Comfort Subscale Scores at the Primary Analysis	Baseline, Up to 24 Months

Collaborators and Investigators

• Sponsor: Ultragenyx Pharmaceutical Inc
• Investigators: Study Director: Medical Director, Ultragenyx Pharmaceutical Inc

Publications and helpful links

Helpful Links

• Ultragenyx Transparency Commitment
• Ultragenyx Osteogenesis Imperfecta (OI) Research Study

Study record dates

Study Major Dates

• Study Start (Actual): June 14, 2023
• Primary Completion (Actual): October 23, 2025
• Study Completion (Estimated): April 1, 2027

Study Registration Dates

• First Submitted: March 3, 2023
• First Submitted That Met QC Criteria: March 3, 2023
• First Posted (Actual): March 14, 2023

Study Record Updates

• Last Update Posted (Actual): February 25, 2026
• Last Update Submitted That Met QC Criteria: February 24, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Connective Tissue Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Collagen Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Skin and Connective Tissue Diseases; Osteogenesis Imperfecta; Organic Chemicals; Organophosphorus Compounds; Organophosphonates; Diphosphonates; setrusumab
• Other Study ID Numbers: UX143-CL314; 2023-504196-24-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No