Clinical trial NCT06636071: Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta
Official title: An Open-label Phase 3 Study of Setrusumab in Pediatric Japanese Subjects With Osteogenesis Imperfecta Type I, III, or IV
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Osteogenesis Imperfecta
Lead sponsor: Ultragenyx Pharmaceutical Inc
Sponsor class: INDUSTRY
First posted: 2024-10-10
Enrollment: 6
Sex: ALL
Minimum age (years): 2
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The primary objective of the study is to evaluate the effect of setrusumab on reduction in fracture rate, including morphometric vertebral fractures.

Detailed description: This study will be conducted in Japan only and consists of a screening period, an open-label treatment period, and an open-label extension period. Participants will receive setrusumab for up to 24 months during the open-label Treatment Period followed by continued setrusumab treatment during the open-label Extension Period. All participants will receive setrusumab until it becomes commercially available in Japan, consent is withdrawn, or the study is otherwise discontinued.

Eligibility criteria: Key Inclusion Criteria:

* Clinical diagnosis of OI Type 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:

* 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 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.
* 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
* Pregnant or nursing

Primary outcomes:
measure: Annualized Rate of All Radiographically-Confirmed Fractures, Including Morphometric Vertebral Fractures During the Treatment Period
timeFrame: Up to Month 24
Secondary outcomes:
measure: Annualized Rate of Radiographically-Confirmed Fractures, Excluding Morphometric Vertebral Fractures During the Treatment Period
timeFrame: Up to Month 24
measure: Change from Baseline in Dual-Energy X-Ray Absorptiometry (DXA) Bone Mineral Density (BMD) Z-Score at the Lumbar Spine During the Treatment Period
timeFrame: Baseline, Month 24
measure: Percent Change from Baseline in DXA BMD at the Lumbar Spine During the Treatment Period
timeFrame: Baseline, Month 24
measure: Serum Setrusumab Concentration Over Time
timeFrame: Up to Month 24
measure: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), and Adverse Events of Special Interest (AESIs), Frequency, Severity and Relationship to Treatment
timeFrame: Up to 36 Months
measure: Incidence of Binding and Neutralizing Anti-Setrusumab Antibodies Over Time
timeFrame: Baseline up to Month 24
Other outcomes:
Locations:
city: Osaka
country: Japan
facility: Osaka Metropolitan University Hospital
city: Osaka
country: Japan
facility: Osaka University Hospital
city: Tokyo
country: Japan
facility: Keio University Hospital
Study officials:
affiliation: Ultragenyx Pharmaceutical Inc
name: Ultragenyx Medical Director
role: STUDY_DIRECTOR
References: