A Randomized, Double-Blind, Dose-Ascending, Placebo-Controlled Phase 1-2 Trial of Inhaled IBIO123: A Monoclonal Antibodies Cocktail Treatment for Mild-To Moderate COVID-19 Illness

Background: Coronavirus 2019 (COVID-19) disease severity is correlated to its respiratory manifestations. Neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) administered systematically have demonstrated clinical efficacy. Immediate and direct delivery of neutralizing antibodies via inhalation may provide additional respiratory clinical benefits.Methods: This double-blind, first-in-human phase 1–2 trial recruited symptomatic and nonhospitalized COVID-19 participants in South Africa and Brazil at 11 centres. Participants were randomly assigned (1:3) to receive single dose placebo or 10 mg of IBIO123 and were characterized for seropositivity against SARS-CoV-2. IBIO123 is a cocktail of three fully human, neutralizing monoclonal antibodies against SARS-CoV-2. Primary virological outcome was the change from baseline to Day 5 in viral load. Secondary clinical outcomes were safety, the effect of IBIO123 on baseline COVID-19 symptoms and disease progression. This trial is now complete and is registered with ClinicalTrials.gov NCT05298813.Findings: Between December 2021 and January 2023, 162 participants were randomized to IBIO123 (122) or placebo (40). Participants at high-risk of severe disease progression constituted 69% of the population. The difference in mean absolute change from baseline viral load (log10 copies/ml) at day 5 between IBIO123 group vs. placebo group was -0.29 (95% confidence interval [CI], −1.32 to 0.75) in overall population and -0.49 (95% confidence interval [CI], − 1.56 to 0.58) in seropositive participants. The proportion of subjects with resolution of respiratory symptoms at day 5 was 30/88 (34%) vs. 4/30 (13%) (hazard ratio [HR] 2.7 [95% CI 1.1–6.8]) between IBIO123 group vs. placebo group in overall population and 17/60 (28%) vs. 1/21 (5%) ([HR] 3.9 [95% CI 1.2–12.6]) among high-risk participants. One death and one hospitalization occurred in the placebo group and none in the IBIO123 group. Number of participants with adverse events was 39 (38%) for IBIO123 group vs. 13 (38%) in placebo.Interpretation: Inhalation of IBIO123 antibody cocktail was safe and provided faster resolution of respiratory symptoms notably among high-risk COVID-19 participants.Trial Registration: This trial is now complete and is registered with ClinicalTrials.gov NCT05298813.Funding: Canadian Strategic Innovation fund and Immune Biosolutions.Declaration of Interest: We declare no competing interests. Ethical Approval: The trial, which was sponsored by Immune Biosolutions, was conducted in accordance with the principles of the Declaration of Helsinki and the ethical guidelines of the Council for International Organizations of Medical Sciences, applicable International Council for Harmonisation Good Clinical Practice guidelines, and applicable laws and regulations. All the patients provided written informed consent.