The angiotensin type 2 receptor agonist C21 restores respiratory function in COVID19 - a double-blind, randomized, placebo-controlled Phase 2 trial

ABSTRACT Background Although several therapies have been evaluated for treatment of COVID-19, the morbidity and mortality in COVID-19 are still significant, and the need for safe and effective drugs remains high even after launch of vaccine programs. Methods We conducted a double-blind, randomized, placebo-controlled trial with the novel oral angiotensin II type 2 receptor agonist C21 in hospitalized COVID-19 patients with C-reactive protein 50-150 mg/L but not needing mechanical ventilation. Patients were randomly assigned to oral C21 (100 mg twice daily) or placebo for 7 days in addition to standard of care, including glucocorticoids and remdesivir. Results 106 patients underwent randomization (51 in the C21 group and 55 in the placebo group). At day 14 after start of treatment, the proportion of patients still requiring supplemental oxygen was significantly reduced by 90% in the C21 group compared to the placebo group (p=0.003). Moreover, fewer patients required mechanical ventilation (one C21 patient and four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one and three deaths in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. Conclusions As studied in hospitalized COVID-19 patients, C21 on top of standard of care led to a clinically beneficial improvement in respiratory function compared to placebo, paving the way for a pivotal randomised controlled trial. This study is registered at ClinicalTrials.gov with identifier NCT04452435 .