Osteogenesis Imperfecta
Conditions
Interventions
Receive treatment with setrusumab 20 mg/kg IV once in a month during Open-Label Treatment Period (up to 24 months.) and Open-Label Extension Period (until setrusumab becomes commercially available in
Sponsors
Vivian Li, MD
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female 2 to = 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 4. Any prior exposure to, or currently receiving, IV-bisphosphonate therapy for treatment of OI 5. 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 6. Must weigh >= 5 kg at Screening
Exclusion criteria
Exclusion criteria: 1. History of skeletal malignancies or bone metastases at any time 2. History of neural foraminal stenosis (except if due to scoliosis) 3. 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. 4. 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 5. 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 6. 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 an 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. 7. Hypocalcemia, defined as serum calcium levels below the age-adjusted normal limit reference ranges after a recommended >= 4 hour fast, at Screening 8. Estimated glomerular filtration rate <= 35 mL/min/1.73 m2 at Screening 9. 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 10. History of external radiation therapy 11. Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the subject at increased risk for adverse effects 12. 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 13. 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) 14. Concurrent participation in another clinical study without prior approval from the study Medical Monitor 15. Pregnant or nursing
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Annualized rate of all radiographically-confirmed fractures, including morphometric vertebral fractures* during the Treatment Period *Morphometric vertebral fracture identified by change from baseline in Genant semi-quantitative scoring based on annual spine radiographs | — |
Secondary
| Measure | Time frame |
|---|---|
| - Annualized rate of radiographically-confirmed fractures, excluding morphometric vertebral fractures* during the Treatment Period - Change from baseline in dual-energy X-ray absorptiometry (DXA) BMD z-score at the lumbar spine during the Treatment Period - Percent change from baseline in DXA BMD at the lumbar spine during the Treatment Period - Serum setrusumab concentration at scheduled time points - Frequency, severity, and relationship to treatment of treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and adverse events of special interest (AESIs) - Incidence of binding and neutralizing anti-setrusumab antibodies at scheduled time points *Morphometric vertebral fracture identified by change from baseline in Genant semi-quantitative scoring based on annual spine radiographs | — |
Contacts
Public ContactClinical trial contact
ICON Clinical Research GK
Outcome results
None listed