臨床研究等提出・公開システム

An Open-label Phase 3 Study of Setrusumab in Pediatric Japanese Subjects with Osteogenesis Imperfecta Type I, III, or IV

Setrusumab in pediatric Japanese subjects with osteogenesis imperfecta

Vivian Li, MD

ICON Clincal Research Limited

4-1-3 Kyuutaromachi, Chuo-ku, Osaka, 541-0056, Japan

Japan-Chiken@iconplc.com

Clinical trial contact

ICON Clinical Research GK

4-1-3 Kyuutaromachi, Chuo-ku, Osaka, 541-0056, Japan

+81-6-4560-2001

Japan-Chiken@iconplc.com

Not Recruiting

Nov. 06, 2024

Interventional

single arm study

open(masking not used)

uncontrolled control

single assignment

treatment purpose

1. Male or female 2 to < 7 years of age at time of informed consent
2. Clinical diagnosis of OI Type I, III, or IV confirmed by identification of genetic mutation in COL1A1 or COL1A2
3. 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
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

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

Both

Osteogenesis Imperfecta

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 Japan)

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

- 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

+81-6-6210-8290

Sept. 09, 2024

No

none