The efficacy and safety of inhaled peptide YKYY017 for COVID-19 patients with mild illness: a phase 2 randomized controlled trial

Abstract

YKYY017 is a SARS-CoV-2 membrane fusion inhibitor. We report efficacy and safety of inhaled YKYY017 for COVID-19 patients with mild to moderate illness from a phase 2 trial (ChiCTR2300075467). 239 patients aged 18-75 years with mostly mild COVID-19 were randomly allocated to receive aerosol inhalation of 10 or 20 mg YKYY017 or placebo once daily. The primary endpoint is the change in SARS-CoV-2 viral load from baseline to Day 4. The mean (±SE) differences in viral load change from baseline were -0.48 ± 0.27 log₁₀ copies/mL (95% CI, -1.01 to 0.06) for the 20 mg group and -0.27 ± 0.27 log₁₀ copies/mL (95% CI, -0.79 to 0.26) for the 10 mg group, compared to the placebo group. Viral load changes at visits other than Day 4 did not differ significantly from placebo in either the 10 or 20 mg YKYY017 groups. The time to sustained symptom recovery was shorter in the 20 mg YKYY017 group (median 117.53, 95%CI 95.33 to 141.45 hours) than in the placebo group (median 143.00, 95%CI 139.17 to 186.87 hours; HR 1.552, 95%CI 1.089 to 2.214, p = 0.0151), whereas the 10 mg YKYY017 group showed a similar but not statistically significant trend compared to placebo (p = 0.0833). The time to sustained symptom alleviation was shorter in both the 20 and 10 mg YKYY017 groups than in the placebo group. The adverse events were mostly mild to moderate. The primary outcome was not met. Following a supplementary phase 1b trial, we are planning another phase 2/3 trial using a twice-daily 20 mg YKYY017 regimen to further assess efficacy and safety.

Fig. 1. Flow chart of the trial.

The modified intention-to-treat (mITT) population included randomized participants who had a positive baseline SARS-CoV-2 PCR test and received at least two doses of YKYY017 or placebo. The per-protocol (PP) population was a subset of the mITT population, comprising participants who had a positive baseline SARS-CoV-2 PCR test, no major protocol deviations, and good adherence to the study regimen. The safety population included all participants who received at least one dose of YKYY017 or placebo and had at least one post-baseline safety assessment.

Fig. 2. Change of viral load (mITT population).

Mean changes are shown for patients with available viral load results in mITT population; I bars indicate standard deviation (upper panel). For the primary outcome (Day 4 viral load reduction), multiple imputations and ANCOVA were used (D4 in lower panel). The number of participants with available viral load results on D4 was 67, 64 and 69 in 10 mg YKYY017 group, 20 mg YKYY017 group and placebo group, respectively. For the secondary viral load outcomes (viral load reduction in other visits), the data were not imputed and ANOVA was used (D6, D8, D11, D15 in lower panel). Two-side 95% confidence intervals (CI) were calculated.

Fig. 3. Survival curve for time to symptom recovery (mITT population).

Kaplan–Meier curve for the time to symptom recovery in mITT population. The time to sustained symptom recovery was shorter in the 20 mg YKYY017 group (median 117.53, 95%CI 95.33 to 141.45 hours) than in the placebo group (median 143.00, 95%CI 139.17 to 186.87 hours; HR 1.552, 95%CI 1.089 to 2.214, p = 0.0151). Compared to the placebo group, the 10 mg YKYY017 group showed a similar but not statistically significant trend (median 118.75, 95%CI 95.68 to 143.32 hours; HR 1.361, 95%CI 0.960 to 1.930, p = 0.0833).

Fig. 4. Survival curve for time to symptom alleviation (mITT population).

Kaplan–Meier curve for the time to symptom alleviation in the mITT population. The time to sustained symptom alleviation was shorter in both the 20 mg (median 96.23, 95%CI 94.82 to 119.63 hours; HR 1.494, 95%CI 1.053 to 2.121, p = 0.0246) and 10 mg (median 115.97, 95%CI 95.20 to 119.70 hours; HR 1.545, 95%CI 1.093 to 2.184, p = 0.0137) YKYY017 groups than in the placebo group (median 119.63, 95%CI 117.28 to 160.15 hours).