CC-31244

Program Discovery Preclinical Phase 1 Phase 2a Phase 3
Hepatitis C CC-31244 - University of MD
(Pan-genotypic NS5B NNI)
Discovery Phase complete
Preclinical Phase complete
Phase 1 Phase complete
Phase 2a Phase in progress
Phase 3 Phase not started
Hepatitis C CC-31244 - Hong Kong
(Pan-genotypic NS5B NNI)
Discovery Phase complete
Preclinical Phase complete
Phase 1 Phase complete
Phase 2a Phase in progress
Phase 3 Phase not started

CC-31244, a non-nucleoside polymerase inhibitor, is a potential best-in-class pan-genotypic inhibitor of NS5B polymerase for the treatment of hepatitis C infection. It has the potential to be an important component in an all-oral ultra-short duration HCV combination therapy.

U.S. Phase 2a Study - University of Maryland

In January 2019, we announced safety and preliminary efficacy data from its triple regimen, U.S. Phase 2a study evaluating CC-31244 and Epclusa (sofosbuvir/velpatasvir) for the ultra-short treatment of HCV infected individuals.

The U.S. Phase 2a study is an open-label study designed to evaluate the safety, tolerability, and preliminary efficacy of CC-31244 and Epclusa, an approved 12-week therapy for HCV developed by Gilead Sciences, Inc., in 12 subjects with treatment-naïve HCV genotype 1. Subjects received oral 400 mg of CC-31244 and Epclusa for 2 weeks. Following this, the subjects continued Epclusa treatment alone for another 4 weeks. All subjects completed the 6-week treatment regimen. The treatment was well tolerated with no study discontinuations due to adverse events. Eight of 12 subjects achieved the primary efficacy endpoint of sustained virologic response at 12 weeks after completion of treatment (SVR12). SVR12 is defined as undetectable virus in blood 12 weeks after completion of treatment and is considered a virologic cure.

In November 2019, we announced new data demonstrating positive results from our triple regimen, U.S. Phase 2a study evaluating CC-31244 and sofosbuvir/velpatasvir (Epclusa) for the ultrashort treatment of HCV infected individuals. Results from the Phase 2a study demonstrated that eight of 12 (67%) patients achieved primary endpoint of sustained virologic response (SVR) 12, which is considered a cure, using only 6 weeks of Epclusa’s therapy combined with only 2 weeks of CC-31244. Patients that achieved SVR had significantly higher frequencies of terminally differentiated effector memory CD8+ T cells compared with those who relapsed at both baseline and at end-of-6-week treatment. At the same time, the frequency of naïve CD8+ T cells was lower while the frequency of effector memory CD8+ T cells was higher in SVR patients; however, these differences were not statistically significant. NK cell cytotoxic phenotypes determined by measuring expression of TRAIL and CD107a also did not differ between SVR and relapse patients, unlike another study that evaluated a different regimen for 12 weeks.

For additional information about the U.S. Phase 2a study of CC-31244 for the treatment of viral hepatitis C, please visit ClinicalTrials.gov and reference identifier NCT03501550.

Investigator-Initiated Hong Kong Phase 2a Study

Patient enrollment has commenced in the investigator-initiated Phase 2a study of CC-31244 in Hong Kong SAR, China. The Phase 2a open-label study is being conducted at the Humanity & Health Research Centre, Humanity and Health Medical Group, in Hong Kong and will evaluate the safety, tolerability and preliminary efficacy of our CC-31244 in combination with Sofosbuvir and Daclatasvir with or without a protease inhibitor, for the treatment of hepatitis C (HepC). Sixteen patients will be enrolled in the Phase 2a study. This trial differs from the University of Maryland Phase 2a trial we are conducting in that the trial will include a protease inhibitor. Under the Clinical Trial Agreement, the Phase 2a study of CC-31244 for the treatment of HepC will be sponsored and conducted by the Humanity & Health Research Centre, Hong Kong under the guidance of George Lau, M.D., FRCP (Edin, Lond), FHKAM (Med), FHKCP, FAASLD, Founding Chairman of Humanity and Health Medical Group, Hong Kong. As part of the agreement, Cocrystal will provide CC-31244, its lead product in development for HepC. Cocrystal’s CC-31244 is an investigational, oral, potent, broad-spectrum replication inhibitor called a non-nucleoside inhibitor (NNI). It has a high barrier to drug resistance designed and developed using our proprietary structure-based drug discovery technology. It is active against HCV genotypes 1-6 with no significant cytotoxicity in multiple cell types at high concentrations.

We previously reported positive data from the Phase 1a/1b trial of CC-31244 for the treatment of chronic hepatitis C infection. The Phase 1a/1b study was a randomized, placebo-controlled, double-blind trial designed to evaluate single and multiple ascending doses of CC-31244 for safety/tolerability, pharmacokinetics, and antiviral activity in hepatitis C infected patients. In Phase 1a, 30 healthy volunteers received single doses (20-400 mg) of CC-31244, and 12 healthy volunteers received repeated doses of CC-31244 (either 200 or 400 mg) for 7 days. In Phase 1b, 15 patients with hepatitis C genotype 1 infection received CC-31244 for 7 days (6, 400 mg daily; 6, 600 mg daily; 3, 200 mg twice daily).

As reported, there were no dose-limiting adverse events, study discontinuations due to adverse events, or serious adverse events. Viral load data showed that CC-31244 administered once daily (400 mg or 600 mg) or twice daily (200 mg) for 7 days had a substantial and durable antiviral effect, with an average hepatitis C RNA viral load decline from baseline of 1000-fold by Day 4. Interestingly, the mean viral load at 6 days after the last dose persisted in the range of 100-fold below baseline. Hepatitis C genotype 1b cell-based replicon assays using combinations of CC-31244 with other classes of hepatitis C drugs showed additive and synergistic effects of CC-31244, providing important information for ultra-short duration therapy cocktail regimens.


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