R7128 trial

I am going for a screening for the new Roche/Pharmasett polymerase inhibitor (R7128) trial. I will find out all the details tomorrow and then decide if I will participate. From what I understand it is going to be using 1000mg of R7128 with pegasys and Copegus for 4 weeks, then just peg and cop for another 4. After that you have the option of continuing on for 40 weeks of peg and cop. They are accepting geno 1 treatment naive and geno 2 and 3 also for this trial.

Here is their press release:
Pharmasset Adds Two Cohorts to R7128 Hepatitis C Study
Two 4-week cohorts will be enrolled to evaluate R7128 1500 mg BID in HCV genotypes 2 and 3 prior non-responders and R7128 1000 mg BID in HCV genotype 1 treatment-naive patients

PRINCETON, N.J. and MILAN, Italy, April 24, 2008 -- Pharmasset, Inc. (Nasdaq: VRUS) will enroll two additional cohorts in the ongoing Phase 1 study protocol to evaluate 4 weeks of combination therapy with R7128. R7128, a prodrug of PSI-6130, is a nucleoside analogue polymerase inhibitor of hepatitis C virus (HCV) that is being developed through Pharmasset's collaboration with Roche.

Cohort 3 will study R7128 1000 mg BID in treatment-naive patients with HCV genotype 1. This cohort is intended to provide clinical antiviral activity data in support of pharmacokinetic models from earlier studies. Cohort 4 will study R7128 1500 mg BID in patients with HCV genotypes 2 and 3 who did not achieve a sustained virologic response (SVR) with previous interferon-based therapy. Cohorts 3 and 4 will both be dosed in combination with Pegasys (peginterferon alfa-2a) plus Copegus (ribavirin).

Patients in Cohorts 3 and 4 are scheduled to begin dosing by the end of May 2008. Preliminary safety and antiviral activity data from the 4-week combination studies are anticipated during the 3rd quarter of 2008. Cohorts 3 and 4 will be conducted in parallel with the global Phase 2b study preparation activities for R7128. The timing of the Phase 2b study is not dependent upon data from Cohorts 3 and 4.

"Our pharmacokinetic modeling of the 500 mg and 1500 mg cohorts of R7128 in combination with Pegasys plus Copegus suggests that the 1000 mg dose could deliver a rapid virologic response (RVR) rate similar to the 1500 mg dose," stated Dr. Michelle Berrey, Pharmasset's Chief Medical Officer. "The confirmatory results from this additional cohort will aid us in selecting the appropriate doses to evaluate in the global Phase 2b study that is being planned to evaluate R7128 in triple combination for up to 12 weeks."

"R7128 is equally potent in vitro against HCV genotypes 1, 2, 3, and 4, and we believe it is clinically and commercially important to test R7128 in patients with these HCV genotypes," stated Schaefer Price, Pharmasset's Chief Executive Officer. "Twenty percent of U.S. HCV-infected patients and approximately 30% of European and Latin American HCV-infected patients have genotypes 2 and 3. These patients are currently treated with 24 weeks of pegylated-interferon plus ribavirin, but 20% of this population fails to achieve an SVR. By potentially addressing this unmet medical need in a patient population for whom the standard of care is only 24 weeks, we could possibly design shorter clinical trials that may provide a quicker path to the market for R7128."

About R7128

R7128 is being developed for the treatment of chronic HCV infection. R7128 is a prodrug of PSI-6130, a cytidine nucleoside analog inhibitor of HCV RNA polymerase. A prodrug is a chemically modified form of a molecule designed to enhance the absorption, distribution and metabolic properties of that molecule. Results from an oral single ascending dose study of PSI-6130 in 24 healthy male volunteers showed that PSI-6130 was generally well tolerated with no serious adverse events in doses up to 3000 mg.

R7128 demonstrated potent, dose-dependent antiviral activity across four prior treatment-failure patient cohorts (n = 40) receiving 750 mg or 1500 mg administered either once-daily or twice-daily for 14 days as monotherapy. The greatest mean decrease in HCV RNA from baseline was demonstrated in the patient cohort that received 1500 mg twice-daily, the highest dose of R7128 administered in the study. These patients demonstrated a mean 2.7 log10 IU/mL (>99%) decrease in HCV RNA. There was no evidence of the development of viral resistance in any dose cohort after 14 days of dosing.

In a 4-week Phase 1 combination study that was conducted in 50 treatment- naive patients chronically infected with HCV genotype 1, R7128 demonstrated potent short-term antiviral activity and was generally safe and well tolerated. Eighty-five percent (85%) of patients receiving R7128 1500 mg twice-daily (BID) with Pegasys plus Copegus for 4 weeks achieved undetectable HCV RNA levels with safety and tolerability comparable to placebo with Pegasys plus Copegus.