Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta

Osteogenesis Imperfecta Clinical Trial

— Cosmic  

Official title:

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05768854
• Other study ID #: UX143-CL314
• Secondary ID: 2023-504196-24-0
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: June 14, 2023
• Est. completion date: June 2026

Study information

• Verified date: May 2024
• Source: Ultragenyx Pharmaceutical Inc
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 69
• Est. completion date: June 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 6 Years

Eligibility

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

Related Conditions & MeSH terms

• Osteogenesis Imperfecta

Intervention

Drug:
• Bisphosphonate
Administered per investigator discretion via intravenous (IV) infusion

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

Locations

Country	Name	City	State
Brazil	Hospital de Clinicas de Porto Alegre (HCPA)	Porto Alegre	Rio Grande Do Sul
Canada	Children's Hospital at London Health Sciences Centre	London	Ontario
Canada	Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa	Ottawa
France	Institut Imagine	Paris
Germany	Universitätsklinikum Köln (University of Cologne) - Children's hospital University	Köln
Italy	Azienda Ospedaliera Universitaria Policlinico Umberto I	Roma
Netherlands	Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis	Utrecht
Poland	Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob Metabolicznych	Lódz
United States	Children's Hospital Colorado	Aurora	Colorado
United States	Shriners Hospitals for Children Chicago	Chicago	Illinois
United States	Cook Children's Medical Center	Fort Worth	Texas
United States	Baylor College of Medicine	Houston	Texas
United States	University of Missouri-Kansas City (UMKC) Medical School - Children's Mercy Hospitals & Clinics (CMHC)	Kansas City	Missouri
United States	Childrens Hospital LA	Los Angeles	California
United States	Vanderbilt University Medical Center (VUMC)	Nashville	Tennessee
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Phoenix Children's Hospital	Phoenix	Arizona
United States	St. Louis Children's Hospital	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	University of South Florida	Tampa	Florida
United States	Children's National Hospital DC	Washington	District of Columbia
United States	Nemours/ Alfred i. duPoint Hospital for Children	Wilmington	Delaware

Sponsors (1)

Lead Sponsor	Collaborator
Ultragenyx Pharmaceutical Inc

Countries where clinical trial is conducted

United States,  Brazil,  Canada,  France,  Germany,  Italy,  Netherlands,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Rate of all Radiographically-confirmed Fractures, Including Morphometric Vertebral Fractures During the Active-controlled Period		Up to 24 Months
Secondary	Annualized Rate of all Radiographically-confirmed Fractures, Excluding Morphometric Vertebral Fractures During the Active-controlled Period		Up to 24 Months
Secondary	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 Month 12 of the Active-controlled Period		Baseline, Up to 12 Months
Secondary	Serum Setrusumab Concentration		Up to 24 Months
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs)		Up to 24 Months
Secondary	Number of Participants With Anti-setrusumab Binding and Neutralizing Antibodies		Up to 24 Months

External Links

•   Ultragenyx Osteogenesis Imperfecta (OI) Research Study Opportunity