Safety and efficacy of inhaled IBIO123 for mild-to-moderate COVID-19: a randomised, double-blind, dose-ascending, placebo-controlled, phase 1/2 trial.

BACKGROUND

COVID-19 severity is associated with its respiratory manifestations. Neutralising antibodies against SARS-CoV-2 administered systemically have shown clinical efficacy. However, immediate and direct delivery of neutralising antibodies via inhalation might provide additional respiratory clinical benefits. IBIO123 is a cocktail of three, fully human, neutralising monoclonal antibodies against SARS-CoV-2. We aimed to assess the safety and efficacy of inhaled IBIO123 in individuals with mild-to-moderate COVID-19.

METHODS

This double-blind, dose-ascending, placebo-controlled, first-in-human, phase 1/2 trial recruited symptomatic and non-hospitalised participants with COVID-19 in South Africa and Brazil across 11 centres. Eligible participants were adult outpatients (aged ≥18 years; men and non-pregnant women) infected with COVID-19 (first PCR-confirmed within 72 h) and with mild-to-moderate symptoms, the onset of which had to be within 10 days of randomisation. Using permuted blocks of four, stratified by site, we randomly assigned participants (1:3) to receive single-dose placebo or IBIO123 (1 mg, 5 mg, or 10 mg) in phase 1, and single-dose placebo or IBIO123 (10 mg) in phase 2, in addition to local standard of care. Participants underwent serological testing to identify antibodies against SARS-CoV-2. Participants, investigators, and the study team were masked to treatment assignment. In phase 1, the primary outcome was the safety assessment in the safety population (ie, all participants who received an intervention). In phase 2, the primary outcome was the mean absolute change from baseline to day 5 in SARS-CoV-2 viral load measured by nasopharyngeal swabs analysed using a mixed model for repeated measures in the full analysis set (FAS; ie, participants with one analysable viral load value at baseline and at least one analysable viral load value at day 3 or day 5). Secondary clinical outcomes included safety from baseline to day 29, assessed by evaluating adverse events; the effect of IBIO123 on baseline COVID-19 symptoms resolution until day 8, with symptoms systemically evaluated by the investigators; and disease progression as measured by the COVID-19 WHO Clinical Progression Scale. For clinical endpoints in phase 2, we used a modified FAS (ie, participants who had at least one analysable viral load value over the course of the study, confirming that they were infected with SARS-CoV-2). This trial is now completed and is registered with ClinicalTrials.gov, NCT05298813.

FINDINGS

Between Dec 4, 2021, and May 23, 2022, 24 participants were enrolled in phase 1. Between July 20, 2022, and Jan 4, 2023, 138 participants were enrolled in phase 2 and five were excluded because they did not meet the inclusion criteria. Participants were randomly assigned to receive IBIO123 (n=18) or placebo (n=6) in phase 1, and randomly assigned to receive IBIO123 (n=104) or placebo (n=34) in phase 2. In phase 2, the study was stopped before reaching the planned accrual because of a decline in COVID-19 incidence. In phase 1, no safety issues were observed. In phase 2, the difference in mean absolute change from baseline viral load to day 5 between participants in the IBIO123 group and participants in the placebo group was -0·29 log

INTERPRETATION

Inhalation of IBIO123 was safe. Despite the lack of significant reduction of viral load at day 5, treatment with IBIO123 resulted in a higher proportion of participants with complete resolution of respiratory symptoms at day 8. This study supports further clinical research on inhaled monoclonal antibodies in COVID-19 and respiratory diseases in general.

FUNDING

Canadian Strategic Innovation Fund and Immune Biosolutions.

Informations de copyright

Copyright © 2023 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests BM, SML, ML, PB, AlF, J-FL, DG, AL, FL, and SG are all employees of Immune Biosolutions. AnF holds patents on mAbs contained in IBIO123 (WO CA2021/051873 and WO CA2022/051074). YS declares no competing interests.