Setrusumab vs Bisphosphonates in Pediatric Subjects With Osteogenesis Imperfecta (Cosmic)
Osteogenesis Imperfecta
About this trial
This is an interventional treatment trial for Osteogenesis Imperfecta
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
Sites / Locations
- Phoenix Children's Hospital
- Childrens Hospital LARecruiting
- Children's Hospital ColoradoRecruiting
- Yale New Haven HospitalRecruiting
- Nemours/ Alfred i. duPoint Hospital for ChildrenRecruiting
- Children's National Hospital DC
- University of South FloridaRecruiting
- Shriners Hospitals for Children ChicagoRecruiting
- University of Missouri-Kansas City (UMKC) Medical School - Children's Mercy Hospitals & Clinics (CMHC)Recruiting
- St. Louis Children's HospitalRecruiting
- Washington University School of MedicineRecruiting
- Vanderbilt University Medical Center (VUMC)Recruiting
- Cook Children's Medical CenterRecruiting
- Baylor College of Medicine
- Hospital de Clinicas de Porto Alegre (HCPA)
- Children's Hospital at London Health Sciences Centre
- Childrens Hospital Of Eastern Ontario Research Institute, University Of Ottawa
- Institut ImagineRecruiting
- Universitätsklinikum Köln (University of Cologne) - Children's hospital University
- Azienda Ospedaliera Universitaria Policlinico Umberto I
- Universitair Medisch Centrum Utrecht (UMCU) - Wilhelmina Kinderziekenhuis
- Uniwersytet Medyczny w Lodzi - Klinika Endokrynologii i Chorob MetabolicznychRecruiting
Arms of the Study
Arm 1
Arm 2
Active Comparator
Experimental
Intravenous Bisphosphonates (IV-BP) -> Setrusumab
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
Participants will receive Setrusumab during the active-controlled and extension period