China-based Ascletis Pharma Inc. (HKG: 1672) has announced the dosing of four healthy subjects in the first cohort of a multi-dose escalation Phase I clinical study for its oral 3-chymotrypsin-like protease (3CLpro) inhibitor ASC11, in combination with 100 mg ritonavir tablets. The study aims to evaluate the safety, tolerability, and pharmacokinetics (PK) of ASC11 as a potential treatment for COVID-19.
Clinical Trial Design and Enrollment
The Phase I clinical trial is expected to enroll 72 healthy subjects, including 60 subjects in single-dose and multiple-dose escalation cohorts, and 12 subjects in a food effect trial. Enrollment is anticipated to be completed in the first quarter of 2023. Among the 60 subjects, 32 will be randomized into four cohorts to receive escalating multiple doses of ASC11, either alone or in combination with 100 mg ritonavir tablets, twice daily (BID) for 5.5 days. The study is randomized, double-blind, and placebo-controlled, with the food effect trial evaluating the impact of food on the PK of ASC11 in combination with ritonavir.
ASC11’s Antiviral Potency and Development
In antiviral cellular assays with infectious SARS-CoV-2, ASC11 demonstrated significantly higher potency against the virus compared to other 3CLpro inhibitors, including Nirmatrelvir, S-217622, PBI-0451, and EDP-235. ASC11 also maintained potent antiviral activity against various Omicron variants, such as BA.1 and BA.5. Animal models infected with SARS-CoV-2 further confirmed ASC11’s potent antiviral activity.
ASC11 is an orally administered small molecule drug candidate discovered in-house by Ascletis using proprietary technologies, including molecular docking. The company has filed global patent applications for ASC11 and related compounds, as well as an Investigational New Drug (IND) application in the US in November of last year.
Future Outlook
The initiation of the Phase I clinical trial for ASC11 marks a significant step forward in Ascletis’ efforts to develop a novel treatment for COVID-19. With its demonstrated antiviral potency and robust clinical trial design, ASC11 has the potential to address significant unmet needs in the ongoing pandemic. Ascletis’ commitment to advancing innovative therapies underscores its role as a leader in the global fight against viral diseases.-Fineline Info & Tech
