The efficacy and safety of levilimab in severely ill COVID-19 patients not requiring mechanical ventilation: results of a multicenter randomized double-blind placebo-controlled phase III CORONA clinical study.

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).

A phase III study of BCD-055 compared with innovator infliximab in patients with active rheumatoid arthritis: 54-week results from the LIRA study.

BCD-055 is a biosimilar of innovator infliximab (IFX). Here we present the 54-week results from phase 3 clinical study in patients with rheumatoid arthritis (RA). The aim of this study was to demonstrate the equivalent efficacy and safety of BCD-055 and IFX in patients with active rheumatoid arthritis. 426 adults with active RA were enrolled. Patients were randomized into 2 study arms in 2:1 ratio to receive BCD-055 or IFX innovator in dose of 3 mg/kg at week 0, 2, 6 and then every 8 weeks up to week 54. Primary efficacy endpoint was the rate of American College of Rheumatology (ACR) 20 response at week 14. The equivalence margin was set as 15%. Immunogenicity and safety were also assessed. Rate of ACR20 at week 14 in PP (Per-Protocol) population was 71.2% in BCD-055 group and 67.9% in IFX group. Difference in ACR20 rates between groups was 3.2% with 95% CI [- 7.0%; 13.5%] (р = 0.587). Throughout 54-week study period, both groups were characterized by similar rates of ACR20/50/70 response at all timepoints without significant differences (p > 0.05). The rates of adverse events (AE) were similar in groups (74.64% in BCD-055 arm vs 66.67% in IFX arm, p = 0.111). Antibodies to infliximab were detected in 28.46% patients for BCD-055 arm and 26.56% for IFX arm (p = 0.786). BCD-055 and IFX were comparable in efficacy (including radiographic progression), safety and immunogenicity throughout the 54-week study.Trial registration ClinicalTrials.gov ID, number NCT02762838.