IMPE2023 Poster Presentations Bone, Growth Plate and Mineral Metabolism (19 abstracts)
Orbit: A Randomized Phase 2/3 Study Consisting of a Phase 2 Single-Blind, Dose-Evaluation Phase and a Phase 3, Double-Blind, Placebo-controlled Phase to Assess the Efficacy and Safety of Setrusumab in Subjects with Osteogenesis Imperfecta
Nicholas Bishop 1 , Eric Rush 2,3,4 , V Reid Sutton 5 , Luca Sangiorgi 6 , Oliver Semler 7 , Gary Gottesman 8 , Hamilton Cassinelli 9 , Arun Mistry 10 , Alastair MacKinnon 10 , Hui Wang 11 , Wendy Putnam 11 , Maurilia Carrabs 11 & Heather Byers 11
1University of Sheffield, Sheffield, United Kingdom. 2Children’s Mercy, Kansas City, USA. 3University of Missouri – Kansas City School of Medicine, Kansas City, USA. 4University of Kansas Medical Center, Kansas City, USA. 5Baylor College of Medicine, Houston, USA. 6Instituto Ortopedico Rizzoli, Bologna, Italy. 7University Hospital, University of Cologne, Cologne, Germany. 8Washington University School of Medicine, St Louis, USA. 9Hospital de Niños Ricardo Gutierrez, Buenos Aires, Argentina. 10Mereo Biopharma, London, United Kingdom. 11Ultragenyx Pharmaceutical Inc, Novato, USA
Setrusumab is a fully human anti-sclerostin monoclonal antibody in development for the treatment of osteogenesis imperfecta (OI). In a Phase 2b study in adults with OI, setrusumab demonstrated robust increases in bone formation, density and strength across OI Types I, III, and IV (NCT03118570). The Orbit study is an operationally seamless Phase 2/3 clinical trial assessing the efficacy and safety of setrusumab in pediatric and young adult participants with OI (NCT05125809). The primary objectives are to identify a setrusumab dose strategy in Phase 2 and to evaluate fracture rate reduction vs placebo in Phase 3. The Phase 2 primary endpoint is percent change in serum amino-terminal propeptide of type 1 procollagen (P1NP) from baseline after 1 month of treatment, data will contribute to defining the dose strategy for Phase 3. The Phase 3 primary endpoint is annualized rate of all radiographically confirmed fractures, excluding morphometric vertebral fractures, during the double-blind treatment period. Patients with OI Types I, III, or IV who are 5 to < 26 years, naïve to bisphosphonates or previously treated with bisphosphonates, who have a history of ≥1 fracture in the prior year, ≥2 fractures in the prior 2 years, or ≥1 tibia, femur, or humerus fracture in the past 2 years, and serum 25-hydroxyvitamin D ≥ 20 ng/mL at the screening visit are being enrolled. Exclusion criteria include history of skeletal malignancies, neural foraminal stenosis, cardiovascular disease, uncontrolled endocrine diseases, hypocalcemia, low glomerular filtration rate (GFR), and clinical manifestations of Chiari malformation or basilar invagination. In Phase 2, ~24 patients are being randomized 1:1 to setrusumab low dose or setrusumab high dose IV monthly. In Phase 3, ~195 patients will be randomized 2:1 to setrusumab (at the selected dosing strategy from the Phase 2 primary analysis) or placebo IV monthly. The Phase 3 primary analysis will occur between Month 12 and 24 for the last patient enrolled, as projected from fracture data collected during the study. All Phase 3 patients will transition to open label setrusumab after the primary analysis or Month 24, whichever comes first. Patients will not receive bisphosphonates during the study. Patients experiencing significant fractures during the Phase 3 double-blind treatment period will be eligible for earlier transition to setrusumab. The first Orbit study subject was randomized in April 2022, and enrollment is ongoing at multiple sites globally.
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