Protection From SARS-CoV-2 Infection With an Oral Nosode (BiosimCovex): A Randomized, Double-Blind, Placebo-Controlled, Phase III Study.

Background and Objectives: This study investigated a potentized, oral homeopathic SARS-CoV-2 nosode (BiosimCovex) for safety, efficacy, and immunogenicity against COVID-19 infection. Methods: A phase III, multicentre, randomised, double-blind, placebo-controlled trial was conducted at 13 sites in India. 2671 unvaccinated, RT-PCR and SARS-CoV-2 antibody-negative participants were randomized 2:1 to receive 6 doses over 3 days of BiosimCovex (1781) or placebo (890). SARS-CoV-2 prevention efficacy was assessed through RT-PCR. Efficacy was defined as 100 x (1-IRR), where IRR is the ratio of positive RT-PCR test rates in the BiosimCovex compared to the placebo group. A two-sided Clopper-Pearson 95% confidence interval was adjusted for surveillance time. Immunogenicity was measured by SARS-CoV-2 antibody conversion at days 15, 30, 45, and 60. Safety was assessed through symptom questionnaires and laboratory studies every 15 days. Illness burden was assessed through symptom diaries. Results: Maximum efficacy occurred at day 45 and was 50.06% overall, 71.88% in individuals aged 18-40 years; and 61.57% in females. By day 45, there were 23 positive RT-PCR cases per group (BiosimCovex 1.3%; placebo 2.6%, Conclusions: A potentized oral nosode was safe and appeared to prevent SARS-CoV-2 infection and be immunogenic over 60 days. Effectiveness was highest at day 45 in females and in the 18- to 40-year-old age group.