The Efficacy and Safety of BCD-180, an Anti-TRBV9+ T cell Monoclonal Antibody, in Patients with Active Radiographic Axial Spondyloarthritis: 36-week Results from the Randomized, Double-Blind, Placebo-Controlled Phase 2 Clinical Study ELEFTA

The study aims to evaluate the clinical efficacy, safety, pharmacokinetics, pharmacodynamics and immunogenicity of seniprutug (BCD-180) in patients with active radiographic axial spondyloarthritis (r-axSpA, or ankylosing spondylitis). MATERIALS AND METHODS: Two hundred sixty patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups to receive either seniprutug (BCD-180) 5 or 7 mg/kg, or placebo. BCD-180 was administered in the respective group dose using a 0-12-36 week regimen. The placebo group patients were switched to BCD-180 5 mg/kg at Week 24, with therapy continued at Week 36. The primary endpoint was the proportion of patients achieving 40% improvement in the Assessment in Spondyloarthritis International Society (ASAS40) score at Week 24. The secondary endpoints included the proportion of patients achieving an ASAS20/40 response, improvement in 5 of 6 ASAS criteria (ASAS5/6), partial remission according to ASAS, ASDAS-CRP clinically important improvement in (Ankylosing Spondylitis Disease Activity Score with C-reactive protein level, ASDAS-CII) and ASDAS-CRP major improvement (ASDAS-MI). An analysis of changes over time in the disease activity status according to ASDAS-CRP, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) scores, as well as changes over time in laboratory markers (CRP and erythrocyte sedimentation rate (ESR)) was also conducted. Safety was assessed based on the frequency and profile of adverse events (AE) and adverse reactions (AR). RESULTS: The proportion of patients who achieved an ASAS40 response at Week 24 on seniprutug (BCD-180) at doses of 7 and 5 mg/kg was 51.4 and 40.8%, respectively, compared with 24% in the Placebo group (p = 0.0012 and p = 0.0417, respectively). Analysis of secondary endpoints showed that the efficacy of BCD-180 at both study doses was statistically significantly superior to placebo in patients with r-axSpA at Week 24 in the following respects: reduction in the proportion of subjects with very high disease activity (ASDAS-CRP > 3.5), achieving ASDAS-CII, ASAS20, ASAS5/6 response. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI score, as well as CRP and ESR levels was demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. The most common AEs were infusion-related reactions, most of which were mild to moderate according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed mainly during the first administration. The proportion of patients with detected binding antibodies was 5.1%. No neutralizing antibodies were detected. CONCLUSIONS: Seniprutug (BCD-180) as a therapy for r-axSpA has demonstrated superiority over placebo in the clinical efficacy, a good safety profile and low immunogenicity.