Ascletis Pharma Inc. has announced the dosing of four healthy subjects in its multiple-dose escalation phase I clinical trial of oral 3-chymotrypsin like protease (3CLpro) inhibitor ASC11 in combination with 100 mg ritonavir tablets for COVID-19.
The phase I clinical trial is expected to enroll 72 healthy subjects, including 60 subjects in single-dose escalation cohorts and multiple-dose escalation cohorts, and 12 subjects in a food effect trial.
The enrollment is expected to be completed in the first quarter of 2023. Among the 60 subjects, 32 will be randomized into four cohorts to receive escalated multiple doses of ASC11 (in combination with or without 100 mg ritonavir tablets) or matching placebo twice daily (BID) for 5.5 days. The clinical trial is a randomized, double-blind and placebo-controlled study to evaluate the safety, tolerability, and pharmacokinetics (PK) of ASC11 in combination with 100 mg ritonavir tablets in healthy subjects.
Higher potency for Ascletis’ ASC11
The 12 subjects in the food effect trial will be randomized to receive ASC11 in combination with ritonavir tablets twice (fed or fasted) to evaluate the food effect on PK of ASC11 in combination with ritonavir tablets in healthy subjects.
In antiviral cellular assays with infectious SARS-CoV-2, ASC11 demonstrated much higher potency against SARS-CoV-2 than other 3CLpro inhibitors including Nirmatrelvir, S-217622, PBI-0451 and EDP-235. ASC11 remains potent antiviral activity against various popular Omicron variants such as BA.1 and BA.5. In the animal model with infectious SARS-CoV-2, ASC11 also showed potent antiviral activity.
Ascletis’ ASC11 is an in-house discovered oral small molecule drug candidate using various proprietary technologies including molecular docking. Ascletis has filed global patent applications for ASC11 and related compounds and their use in viral disease.
“We are excited that our COVID-19 drug candidates, ASC10 (RdRp inhibitor) and ASC11 (3CLpro inhibitor), which are discovered and developed in-house and with global patents, both have entered into clinical development, which again marks a great recognition to our in-house R&D capabilities in viral diseases. As COVID-19 pandemic causes persistent huge social and economic implications globally, Ascletis will accelerate our clinical development to fight against the pandemic in China and other countries.” said Jinzi J. Wu, founder, chairman and CEO of Ascletis.
Supply agreement
Ascletis has also announced that its wholly owned subsidiary Ascletis Pharmaceuticals Co., Ltd. has entered into a supply agreement of ritonavir tablets with Hainan Simcere Pharmaceutical Co., Ltd., a subsidiary of Simcere Pharmaceutical Group Limited.
Ritonavir is a pharmacokinetic booster of multiple oral antiviral protease inhibitors. Ascletis currently owns the only authorized ritonavir oral tablet in China, which has passed bioequivalence study.