Oral C21 for 7 days did not significantly reduce CRP compared to placebo in hospitalized COVID-19 patients (81% vs 78% reduction; treatment effect ratio 0.85, 90% CI 0.57-1.26).
RCT (n=106)
Double-blind
parallel group
Yes
Does oral angiotensin II type 2 receptor agonist C21 reduce CRP in hospitalized patients with COVID-19?
In hospitalized COVID-19 patients, 7-day treatment with the angiotensin II type 2 receptor agonist C21 did not significantly reduce CRP levels compared to placebo, though post-hoc analyses suggested a potential reduction in the need for supplemental oxygen.
Effect estimate: Treatment effect ratio 0.85 (95% CI 0.57-1.26)
Absolute Event Rate: 81% vs 78%
BACKGROUND: COVID-19 morbidity and mortality remains high and the need for safe and effective drugs continues despite vaccines. METHODS: Double-blind, placebo-controlled, multi-centre, randomised, parallel group phase 2 trial to evaluate safety and efficacy of oral angiotensin II type 2 receptor agonist C21 in hospitalized patients with COVID-19 and CRP ≥ 50-150 mg/L conducted at eight sites in India (NCT04452435). Patients were randomly assigned 100 mg C21 bid or placebo for 7 days in addition to standard of care. Primary endpoint: reduction in CRP. The study period was 21 July to 13 October 2020. FINDINGS: 106 patients were randomised and included in the analysis (51 C21, 55 placebo). There was no significant group difference in reduction of CRP, 81% and 78% in the C21 and placebo groups, respectively, with a treatment effect ratio of 0.85 90% CI 0.57, 1.26. In a secondary analysis in patients requiring supplemental oxygen at randomisation, CRP was reduced in the C21 group compared to placebo. At the end of the 7-day treatment, 37 (72.5%) and 30 (54.5%) of the patients did not require supplemental oxygen in the C21 and placebo group, respectively (OR 2.20 90% CI 1.12, 4.41). A post hoc analysis showed that at day 14, the proportion of patients not requiring supplemental oxygen was 98% and 80% in the C21 group compared to placebo (OR 12.5 90% CI 2.9, 126). Fewer patients required mechanical ventilation (one C21 patient; four placebo patients), and C21 was associated with a numerical reduction in the mortality rate (one vs three in the C21 and placebo group, respectively). Treatment with C21 was safe and well tolerated. INTERPRETATION: Among hospitalised patients with COVID-19 receiving C21 for 7 days there was no reduction in CRP compared to placebo. However, a post-hoc analysis indicated a marked reduction of requirement for oxygen at day 14. The day 14 results from this study justify further evaluation in a Phase 3 study and such a trial is currently underway. FUNDING: Vicore Pharma AB and LifeArc, UK.
Tornling et al. (Mon,) conducted a rct in COVID-19 (n=106). C21 (angiotensin II type 2 receptor agonist) vs. Placebo was evaluated on Reduction in CRP (Treatment effect ratio 0.85, 95% CI 0.57-1.26). Oral C21 for 7 days did not significantly reduce CRP compared to placebo in hospitalized COVID-19 patients (81% vs 78% reduction; treatment effect ratio 0.85, 90% CI 0.57-1.26).