Objective and design: The aim of this double-blind, placebo-controlled, phase III CORONA clinical trial was to evaluate the efficacy and safety of IL-6 receptor inhibitor levilimab (LVL) in subjects with severe COVID-19. Subjects: The study included 217 patients. The eligible were men and non-pregnant women aged 18 years or older, hospitalized for severe COVID-19 pneumonia. Treatment: 206 subjects were randomized (1:1) to receive single subcutaneous administration of LVL 324 mg or placebo, both in combination with standard of care (SOC). 204 patients received allocated therapy. After the LVL/placebo administration in case of deterioration of symptoms, the investigator could perform a single open-label LVL 324 mg administration as the rescue therapy. Methods: The primary efficacy endpoint was the proportion of patients with sustained clinical improvement on the 7-category ordinal scale on Day 14. All efficacy data obtained after rescue therapy administration were considered missing. For primary efficacy analysis, all subjects with missing data were considered non-responders. Results: 63.1% and 42.7% of patients in the LVL and in the placebo groups, respectively, achieved sustained clinical improvement on Day 14 (P = .0017). The frequency of adverse drug reactions was comparable between the groups. Conclusion: In patients with radiologically confirmed SARS-CoV-2 pneumonia, requiring or not oxygen therapy (but not ventilation) with no signs of other active infection administration of LVL + SOC results in an increase of sustained clinical improvement rate. Trail registration: The trial is registered at the US National Institutes of Health (ClinicalTrials.gov; NCT04397562).

The aim – to evaluate the clinical effectiveness, safety, pharmacokinetics, pharmacodynamics, and immunogenicity of seniprutug (BCD-180) in patients with radiographic active axial spondyloarthritis (r-axSpA, or ankylosing spondylitis).Subjects and methods. 260 patients with active r-axSpA and inadequate response to nonsteroidal anti-inflammatory drugs (NSAIDs) were randomized into three groups: seniprutug (BCD-180) at doses of 5 mg/kg or 7 mg/kg, or placebo. BCD-180 was administered on weeks 0–12–36. Patients in the placebo group were switched to BCD-180 at a dose of 5 mg/kg at week 24 and continued therapy at week 36. The primary endpoint was the proportion of patients achieving 40% improvement by Assessment in Spondyloarthritis International Society scale (ASAS40) at week 24. Secondary endpoints were proportion achieving ASAS20/40, improvement of 5 out of 6 criteria of ASAS (ASAS5/6), ASAS partial remission, clinically important improvement in ASDAS-CRP (Ankylosing Spondylitis Disease Activity Score with C-reactive protein) (ASDAS-CII) and major improvement in ASDAS-CRP (ASDAS-MI). The dynamics of the disease activity status according to ASDAS-CRP, the BASDAI (Bath Ankylosing Spondylitis Disease Activity Index) and BASFI (Bath Ankylosing Spondylitis Functional Index) indices, as well as the dynamics of laboratory markers (C-reactive protein anderythrocyte sedimentation rate (ESR)) were analyzed. Safety was assessed by the frequency and profile of adverse events (AEs) and adverse reactions (ARs).Results. The proportion of patients achieving ASAS40 at week 24 with seniprutug (BCD-180) at the dose of 7 mg/kg 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 in patients with r-axSpA, BCD-180 at both study doses was significantly superior to placebo at week 24 in the following measures: decrease in the proportion of subjects with very high disease activity (ASDAS-CRP>3.5) achieving ASDAS-CII, ASAS20, ASAS5/6. A statistically significant decrease in the ASDAS-CRP, BASDAI, BASFI indices, as well as the concentration of CRP and ESR were demonstrated. Tolerability of seniprutug therapy was assessed as acceptable. Infusion reactions were the most common observed adverse events, the vast majority of which were mild to moderate in severity according to CTCAE 5.0 (Common Terminology Criteria for Adverse Events) and developed predominantly during the first administration. The proportion of patients with binding antibodies was 5.1%. However, no neutralizing antibodies were detected.Conclusion. Seniprutug (BCD-180) demonstrated superiority over placebo in clinical efficacy with a favorable safety profile and low immunogenicity as a treatment of r-axSpA.

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). . 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). 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. . 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.

ЦЕЛЬ ИССЛЕДОВАНИЯ Определение оптимальной терапевтической дозы анти-B-клеточного препарата дивозилимаб (ДИВ) на основании данных об эффективности и безопасности внутривенного введения в дозе 125 или 500 мг пациентам с рассеянным склерозом с обострениями (РСО) в сравнении с показателями плацебо (ПБО) и препарата терифлуномид (ТРФ) в течение 24 нед. МАТЕРИАЛ И МЕТОДЫ Проведено многоцентровое рандомизированное двойное слепое и двойное маскированное плацебо-контролируемое клиническое исследование (КИ) 2-й фазы BCD-132-2, включавшее 271 взрослого пациента с РСО, распределенных в соотношении 2:2:2:1 в 4 группы: ТРФ, ДИВ 125 мг, ДИВ 500 мг и ПБО. После скринингового обследования пациентов включали в основной период, состоявший из одного цикла терапии в течение 24 нед. Первичной конечной точкой являлось общее количество накапливающих гадолиний (Gd+) очагов в режиме T1 (per scan), выявленное при выполнении МРТ головного мозга после 24 нед заслепленного применения препаратов ДИВ, ТРФ и ПБО. РЕЗУЛЬТАТЫ Завершили 24 нед терапии 263 пациента. Результаты КИ продемонстрировали отсутствие Gd+ в T1-режиме очагов у большинства пациентов, получавших ДИВ (94,44% в группе ДИВ 125 мг и 93,06% в группе ДИВ 500 мг), после 24 нед лечения, что было статистически значимо выше, чем в группах ТРФ и ПБО (68,06 и 56,36% соответственно, оба — p<0,05). Доля пациентов без подтвержденных обострений в группах ДИВ 125 мг и ДИВ 500 мг составила 93,06 и 97,22% соответственно. ДИВ в обеих дозах оказывал ожидаемый эффект в виде снижения уровня CD19+ B-клеток, однако скорость проявления признаков репопуляции CD19+ B-клеток в группе ДИВ 125 мг была более высокой (в основном за счет восстанавливающегося пула CD27-наивных B-клеток), чем в группе ДИВ 500 мг. ДИВ в обеих дозах показал благоприятный профиль безопасности. ЗАКЛЮЧЕНИЕ Результаты 24 нед терапии свидетельствуют, что ДИВ представляет высокоэффективный, безопасный и удобный в применении препарат для лечения пациентов с РСО, ранее как получавших, так и не получавших терапию препаратами, изменяющими течение рассеянного склероза. Для дальнейшего изучения эффективности и безопасности терапии в рамках КИ 3-й фазы рекомендована доза 500 мг.

Levilimab (LVL) is a monoclonal antibody against the interleukin-6 receptor (IL6R). The article presents data obtained during 56 weeks of the AURORA phase II study.Objective: to evaluate the efficacy safety and immunogenicity of LVL in methotrexate (MTX) resistant patients with active rheumatoid arthritis (RA).Materials and methods. 105 patients with active RA were randomized in a 1:1:1 ratio into two LVL or placebo groups. LVL was administered subcutaneously at a dose of 162 mg every week (QW) or every other week (Q2W). All patients received MTX. After evaluating the primary endpoint of 20% improvement in ACR criteria (ACR20) at week 12, patients in the placebo group were switched to LVL Q2W. The study duration was 56 weeks. The frequency, profile, degree and severity of adverse events were determined in each group for safety assessment. The immunogenicity of LVL was determined by the proportion of patients with identified binding and neutralizing antidrug antibodies. Results. LVL in both regimens was superior to placebo. At week 12, the incidence of ACR20 achievement was 77.1% (LVL QW), 57.1% (LVL Q2W), and 17.1% (placebo) with 95% confidence intervals [37.53; 82.54] (p<0.0001) and [19.08; 68.42] (p=0.003) for the effect difference between LVL and placebo groups. The clinical response, more pronounced in the LVL QW group, persisted until week 52 with an increase in the proportion of patients with ACR50/70, low activity and RA remission. The most common treatment-related adverse events were laboratory abnormalities (predominantly grade 1–2) such as neutropenia, elevated alanine aminotransferase, aspartate aminotransferase levels, hypercholesterolemia, and elevated triglyceride levels. Antidrug antibodies were not identified.Conclusion. In MTX-resistant patients with active RA, the efficacy of both LVL regimens at a dose of 162 mg in combination with MTX was significantly superior to MT monotherapy. LVL QW lead to highest treatment response. LVL has been shown to be well tolerated and low immunogenicity. LVL safety profile is similar to IL6R inhibitors.