title: BPS804 Anti-Sclerostin Antibody in Adults With Moderate Osteogenesis Imperfecta: Results of a Randomized Phase 2a Trial.
abstract: 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.
authors.affiliation: Research Centre, Shriners Hospital for Children, and McGill University, Montreal, QC, Canada.
authors.forename: Francis H
authors.identifier: http://orcid.org/0000-0001-6616-3484
authors.initials: FH
authors.lastname: Glorieux
authors.affiliation: Université Catholique de Louvain, Saint-Luc University Hospital, Brussels, Belgium.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Devogelaer
authors.affiliation: Research Centre, Shriners Hospital for Children, and McGill University, Montreal, QC, Canada.
authors.forename: Michaela
authors.initials: M
authors.lastname: Durigova
authors.affiliation: Ghent University Hospital, Ghent, Belgium.
authors.forename: Stefan
authors.initials: S
authors.lastname: Goemaere
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Sarah
authors.initials: S
authors.lastname: Hemsley
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Experimental and Clinical Osteology, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Franz
authors.initials: F
authors.lastname: Jakob
authors.affiliation: Novartis Institutes for BioMedical Research, Basel, Switzerland.
authors.forename: Uwe
authors.initials: U
authors.lastname: Junker
authors.affiliation: Pacific Pharma Group, Tacoma, WA, USA.
authors.forename: Jon
authors.initials: J
authors.lastname: Ruckle
authors.affiliation: Orthopedic Center for Musculoskeletal Research, Experimental and Clinical Osteology, Orthopedic Department, University of Wuerzburg, Wuerzburg, Germany.
authors.forename: Lothar
authors.initials: L
authors.lastname: Seefried
authors.affiliation: Anaheim Clinical Trials, Anaheim, CA, USA.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Winkle
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000293:Adolescent; D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D015519:Bone Density / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins / Q000037:antagonists & inhibitors*; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D015675:Osteocalcin / Q000097:blood; D010013:Osteogenesis Imperfecta / Q000097:blood / Q000188:drug therapy*; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000911:Antibodies, Monoclonal; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; D010446:Peptide Fragments; D011347:Procollagen; C422903:SOST protein, human; C042813:procollagen type I carboxy terminal peptide; D015675:Osteocalcin; D000469:Alkaline Phosphatase; C000622723:setrusumab
keywords: ANTI-SCLEROSTIN ANTIBODY; CLINICAL TRIALS; DXA; OSTEOGENESIS IMPERFECTA; WNT