Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta

Study Overview
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Brief Summary
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The primary objective of the study is to evaluate bone mineral density (BMD) after 12 months of retreatment with monthly setrusumab in adults with osteogenesis imperfecta (OI).

Detailed Description
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UX143-CL203 is a long-term extension study in adults with OI who participated in the ASTEROID study (also referred to as MBPS205) [NCT03118570]. The UX143-CL203 study comprises Observation, Retreatment, and Extension Periods. There is no intervention during the Observation Period. During the single-arm Retreatment Period, participants receive open-label setrusumab once a month (QM) for 12 months. Following the Retreatment Period, participants enter an Extension Period in which they will continue treatment with open-label setrusumab at different dosing frequencies.

Official Title
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A Phase 2b, Multicenter, Long-term Extension Study of Setrusumab in Adults With Type I, III, or IV Osteogenesis Imperfecta

Conditions
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Osteogenesis Imperfecta

Intervention / Treatment
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* Biological: Setrusumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females who participated in the Phase 2b ASTEROID study Females of childbearing potential must consent to use highly effective contraception during the Observation, Retreatment, and Extension Periods through 2 months after the last dose of setrusumab and agree not to become pregnant Exclusion Criteria: Known hypersensitivity to setrusumab or its excipients that, in the judgment of the Investigator, places the participant 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 Pregnant or breastfeeding or planning to become pregnant (self or partner) at any time during the study Not willing or able to discontinue bisphosphonates 6 months prior to the Retreatment Screening Visit Once enrolled in UX143-CL203, individuals who meet any of the following exclusion criteria will not be eligible to participate in the Retreatment Period: Concurrent participation in any study that is examining the safety and efficacy of any investigational product or investigational medical device that alters bone health during the Retreatment and Extension Periods, per discretion of the Investigator in consultation with the Medical Monitor. Calcium levels outside the normal range at the Retreatment Screening Visit. If the participant's calcium level is not within the normal range, decision to retest should be made in conjunction with the Medical Monitor Glomerular filtration rate (GFR) ≤ 29 mL/min at the Retreatment Screening Visit. If the participant's GFR is ≤ 29 mL/min, decision to retest should be made in conjunction with the Medical Monitor History of skeletal malignancies or bone metastases at any time History of neural foraminal stenosis (except if due to scoliosis) History of myocardial infarction, angina pectoris, ischemic stroke or transient ischemic attack (Investigators should consider whether the potential benefits of treatment outweigh the potential risks in patients with other cardiovascular risk factors such as hypertension, hyperlipidemia, familial hyperlipidemia, family history of premature ischemic cardiovascular disease, smoking, diabetes mellitus, and metabolic syndrome.) History of or concomitant uncontrolled diseases such as hypo-/hyperparathyroidism, hypo-/hyperthyroidism, Paget's disease, abnormal thyroid function or thyroid disease or other endocrine disorders or conditions that could affect bone metabolism eg, Stage IV/V renal disease A history of rickets or osteomalacia or any skeletal condition (other than OI) leading to long-bone deformities and/or increased risk of fractures Documented alcohol and/or drug abuse within 12 months prior to dosing or evidence of such abuse as indicated by the laboratory results during the screening/baseline assessments Documented history of significant psychiatric or medical disorder that would prevent the participant complying with the requirements of the protocol or would make it unsafe for the participant to participate in the study as judged by the investigator Current/previously reported allergy to the study drug or any of its excipients or the class of drug under investigation History of external radiation

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Setrusumab QM -->Setrusumab QM<br>During Retreatment Period: Setrusumab will be administered via intravenous (IV) infusion once a month (QM) for 12 months. During Extension Period: Setrusumab will be administered via IV infusion QM for at least 12 months or until commercially available. | Biological: Setrusumab<br>* A fully human anti-sclerostin monoclonal antibody (mAb)<br>* Other names: BPS804;|
| Experimental: Setrusumab QM --> Setrusumab TBD<br>During Retreatment Period: Setrusumab will be administered via IV infusion QM for 12 months. During Extension Period: Setrusumab will be administered via IV infusion at a dose frequency to be determined (TBD) for at least 12 months or until commercially available. | Biological: Setrusumab<br>* A fully human anti-sclerostin monoclonal antibody (mAb)<br>* Other names: BPS804;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Retreatment Baseline in Lumbar Spine Bone Mineral Density (BMD) Measured by Dual-Energy X-Ray Absorptiometry (DXA) After 12 Months of Setrusumab |  | Retreatment Baseline, Month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage Change From Retreatment Baseline in Total Hip BMD Measured by DXA at Month 12 of the Retreatment Period |  | Retreatment Baseline, Month 12 | 
| Annualized New Fracture Rate as Confirmed by Radiograph During the Retreatment Period |  | Up to Month 12 |