RBD-specific polyclonal F(ab´) 2 fragments of equine antibodies in patients with moderate to severe COVID-19 disease: A randomized, multicenter, double-blind, placebo-controlled, adaptive phase 2/3 clinical trial

LOPARDO, GUSTAVO; COLONNA, MARIANA; CAHN, PEDRO; BELLOSO, WALDO H.; SANGUINETTI, SANTIAGO; SPATZ, LINUS; NANNINI, ESTEBAN; SUED, OMAR; GOLDBAUM, FERNANDO

EClinicalMedicine

Elsevier, Ltd (The Lancet)

Año: 2021 vol. 34

Background: passive immunotherapy is a therapeutic alternative for patients with COVID-19. Equine polyclonal antibodies (EpAbs) could represent a source of scalable neutralizing antibodies against SARS-CoV-2.Methods: we conducted a double-blind, randomized, placebo-controlled trial to assess efficacy and safety of EpAbs (INM005) in hospitalized adult patients with moderate and severe COVID-19 pneumonia in 19 hospitals of Argentina. Primary endpoint was improvement in at least two categories in WHO ordinal clinical scale at day 28 or hospital discharge (ClinicalTrials.gov number NCT04494984).Findings: between August 1st and October 26th, 2020, a total of 245 patients were enrolled. Enrolled patients were assigned to receive two blinded doses of INM005 (n = 118) or placebo (n = 123). Median age was 54 years old, 65?1% were male and 61% had moderate disease at baseline. Median time from symptoms onset to study treatment was 6 days (interquartile range 5 to 8). No statistically significant difference was noted between study groups on primary endpoint (risk difference [95% IC]: 5?28% [-3?95; 14?50]; p = 0?15). Rate of improvement in at least two categories was statistically significantly higher for INM005 at days 14 and 21 of follow-up. Time to improvement in two ordinal categories or hospital discharge was 14?2 (± 0?7) days in the INM005 group and 16?3 (± 0?7) days in the placebo group, hazard ratio 1?31 (95% CI 1?0 to 1?74). Subgroup analyses showed a beneficial effect of INM005 over severe patients and in those with negative baseline antibodies. Overall mortality was 6?9% the INM005 group and 11?4% in the placebo group (risk difference [95% IC]: 0?57 [0?24 to 1?37]). Adverse events of special interest were mild or moderate; no anaphylaxis was reported.Interpretation: Albeit not having reached the primary endpoint, we found clinical improvement of hospitalized patients with SARS-CoV-2 pneumonia, particularly those with severe disease.