Late Breaking Abstract - Immunomodulatory and clinical effects of RIPK1 inhibitor SAR443122 in patients with severe COVID-19

Abstract

<b>Background:</b> Selective inhibition of Receptor interacting serine/threonine protein kinase 1 (RIPK1) could alleviate the hyperinflammatory syndrome occurring in patients with severe coronavirus 2019 (COVID-19). <b>Aim:</b> To explore safety, immunomodulatory and clinical effects of RIPK1 inhibitor, SAR443122 in patients with severe COVID-19. <b>Methods:</b> Patients were randomised (2:1) to receive SAR443122 600mg (300mg twice daily; treatment) or placebo up to 14 days (D; NCT04469621). Safety was assessed up to 28D. The primary outcome was relative change from baseline in C-reactive protein (CRP) level on D7. The time to clinical improvement using 7-point ordinal scale, ventilator/respiratory failure free days (VFD/RFFD), change in SpO₂/FiO₂ ratio, biomarkers (LDH, IL-6, IL-8) were also explored. <b>Results:</b> The treatment difference in relative change from baseline in CRP is shown in Table. Median time to 50% decrease in CRP level from baseline was 3 vs 5D (p=0.056) in treatment vs placebo groups. Median time for ≥2-point improvement in 7-point scale was 8 vs 10D in treatment vs placebo (p=0.38). Consistent trends towards greater improvements were observed in treatment vs placebo in mean VFD/RFFD, change in SpO₂/FiO₂ ratio and biomarkers (Table). SAR443122 was considered safe and well tolerated. <b>Conclusion:</b> These preliminary results indicate the need for a larger confirmatory trial to further assess clinically significant effects.