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BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial.

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Glorieux, Francis H Devogelaer, Jean-Pierre [UCL] Durigova, Michaela Goemaere, Stefan Hemsley, Sarah Winkle, Peter J

This 21-week, open-label, phase 2a trial aimed to evaluate the pharmacodynamics and safety of multiple, escalating infusions of BPS804, a neutralizing, anti-sclerostin antibody, in adults with moderate osteogenesis imperfecta (OI). Patients received BPS804 (three escalating doses each separated by 2 weeks [5, 10, and 20 mg/kg]) or no treatment (reference group). The primary efficacy endpoints were mean changes from baseline to day 43 in: procollagen type 1 N-terminal propeptide (P1NP), procollagen type 1 C-terminal propeptide (P1CP), bone-specific alkaline phosphatase (BSAP), osteocalcin (OC), and type 1 collagen cross-linked C-telopeptide (CTX-1). Mean change from baseline to day 141 in lumbar spine areal bone mineral density (aBMD) was also assessed. BPS804 safety and tolerability were assessed every 2 weeks. Overall, 14 adults were enrolled (BPS804 group: n = 9, mean age 30.7 years, mean aBMD Z-score -2.6; reference group, n = 5, mean age 27.4 years, mean aBMD Z-score -2.2). In the BPS804 group, P1NP, P1CP, BSAP, and OC were increased by 84% (p < 0.001), 53% (p = 0.003), 59% (p < 0.001), and 44% (p = 0.012), respectively, versus baseline (reference: P1NP, +6% [p = 0.651]; P1CP, +5% [p = 0.600]; BSAP, -13% [p = 0.582]; OC, -19% [p = 0.436]). BPS804 treatment downregulated CTX-1 by 44% from baseline (reference: -7%; significance was not tested for this biomarker), and increased aBMD by 4% (p = 0.038; reference group: +1%; p = 0.138). BPS804 was generally well tolerated. There were 32 adverse events reported in nine patients; none was suspected to be treatment-related. There were no treatment-related fractures. BPS804 stimulates bone formation, reduces bone resorption, and increases lumbar spine aBMD in adults with moderate OI. This paves the way for a longer-term, phase 3 trial into the efficacy, safety, and tolerability of BPS804 in patients with OI. © 2017 American Society for Bone and Mineral Research.

Document type Article de périodique (Journal article) – Article de recherche
Access type Accès libre
Publication date 2017
Language Anglais
Journal information "Journal of Bone and Mineral Research" - Vol. 32, no.7, p. 1496-1504 (2017)
Peer reviewed yes
Publisher American Society for Bone and Mineral Research ((United States) Washington, DC)
issn 0884-0431
e-issn 1523-4681
Publication status Publié
Affiliations UCL - SSS/IREC/RUMA - Pôle de Pathologies rhumatismales
UCL - (SLuc) Service de rhumatologie
MESH Subject Adolescent ; Adult ; Alkaline Phosphatase ; Antibodies, Monoclonal ; Bone Density ; Bone Morphogenetic Proteins ; Female ; Genetic Markers ; Humans ; Male ; Osteocalcin ; Osteogenesis Imperfecta ; Peptide Fragments ; Procollagen
Keywords Anti-sclerostin antibody ; Clinical trials ; DXA ; Osteogenesis Imperfecta ; WNT
Links
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Bibliographic reference Glorieux, Francis H ; Devogelaer, Jean-Pierre ; Durigova, Michaela ; Goemaere, Stefan ; Hemsley, Sarah ; et. al. BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial.. In: Journal of Bone and Mineral Research, Vol. 32, no.7, p. 1496-1504 (2017)
Permanent URL http://hdl.handle.net/2078.1/203752