Phase IIb Trial Will Further Assess Efficacy, Safety And Tolerability Of MK-7009 - For Patients With Chronic Hepatitis C

Main Category: Liver Disease / Hepatitis
Also Included In: Clinical Trials / Drug Trials
Article Date: 11 May 2009 - 3:00 PDT

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Results from an ongoing Phase IIa study showed that MK-7009, Merck Sharp and Dohme's (MSD) investigational oral hepatitis C virus (HCV) protease inhibitor, in combination therapy significantly improved rapid viral response, defined as viral suppression to undetectable levels within 28 days, compared to placebo in combination therapy in previously untreated (treatment-naïve) patients infected with chronic HCV genotype 1, one of the most difficult to treat genotypes of HCV (p<0.0001). All patients received MK-7009 or placebo in combination with pegylated interferon and ribavirin (peg-IFN/RBV), the current standard of care for treatment of HCV infection. (Poster 2701) These findings were presented today at the 44th Annual European Association for the Study of the Liver (EASL) meeting in Copenhagen, Denmark.

According to the World Health Organization, an estimated 180 million people are infected with HCV worldwide, 130 million of whom are chronic HCV carriers at risk of developing liver cirrhosis and/or liver cancer. It is estimated that three to four million persons are infected each year.

"In this ongoing study, MK-7009 in combination therapy rapidly lowered and generally maintained the amount of virus in the blood to below detectable levels in previously untreated HCV patients," said Robin Isaacs, vice president and therapeutic head for Infectious Diseases, Merck Research Laboratories. "These preliminary results help us understand the efficacy and tolerability profile of MK-7009 and support the further development of MK-7009 for the treatment of HCV."

These findings are the primary analysis from an ongoing, randomized, placebo-controlled, double-blind study of MK-7009 in treatment-naïve, chronic HCV patients. In this study, 95 patients were randomized across five treatment arms with regimens of MK-7009 300 mg or 600 mg twice daily, MK-7009 600 mg or 800 mg once daily, or placebo, for 28 days. Patients in all treatment arms received standard doses of peg-IFN/RBV in combination with the MK-7009 or placebo regimens, and are continuing to receive peg-IFN/RBV for an additional 44 weeks. HCV RNA was measured by the HCV RNA PCR TaqMan 2.0 assay, which has a lower limit of detection (LLOD) of 10 IU/mL and a lower limit of quantification (LLOQ) of 25 IU/mL. The primary endpoint of the study was reduction in HCV RNA to undetectable levels (<10 IU/mL) at day 28.

Suppression of viral load to undetectable levels by day 28

After 28 days of therapy, 69 to 82 percent of patients in the regimens containing MK-7009 (n= 68 included in the per-protocol analysis) versus 6 percent of patients in the placebo regimen (n=18 included in the per-protocol analysis) achieved undetectable HCV RNA levels (p<0.0001). More than 80 percent of patients in the regimens containing MK-7009 versus 11 percent of patients in the placebo regimen experienced viral suppression to below LLOQ (<25 IU/mL) on day 28.

Viral suppression continued in the majority of patients following termination of MK-7009 treatment at day 28. At day 42, HCV RNA was undetectable in 77 to 94 percent of the patients in the regimens that had contained MK-7009 versus 12 percent of patients in the regimen that had contained placebo (p<0.0001). Additionally, all subjects in the 600 mg twice daily regimen group achieved HCV RNA to below LLOQ (<25 IU/ml) from Day 21 through Day 42.

Tolerability and safety profile of MK-7009

There were no serious adverse events and no discontinuations due to an adverse event during the first 42 days of the study. The most commonly reported adverse experiences (> 20 percent in one or more treatment arms) in patients receiving MK-7009 versus patients receiving placebo, respectively, were nausea (28 to 40 percent versus 26 percent), headache (16 to 45 percent versus 37 percent), fatigue (5 to 35 percent versus 32 percent), flu-like symptoms (20 to 26 percent versus 16 percent), anorexia (5 to 25 percent versus 11 percent), diarrhea (6 to 25 percent versus 21 percent), indigestion (0 to 22 percent versus 21 percent), rash (10 to 17 percent versus 21 percent), and vomiting (0 to 40 percent versus 5 percent). The incidence of vomiting was higher in the treatment arm containing MK-7009 600 mg twice daily (40 percent) versus the treatment arm containing placebo (5 percent); vomiting did not require anti-emetic treatment and did not lead to discontinuation or dose reduction of MK-7009.

Phase IIb study to further assess efficacy, safety and tolerability of MK-7009

A Phase IIb study has been initiated to evaluate the safety, tolerability and efficacy of MK-7009 when administered concomitantly with peg-IFN/RBV to previously treated (treatment-experienced) patients with chronic hepatitis C genotype 1 infection. Patients will receive either placebo or MK-7009 at 300 mg or 600 mg twice daily in combination with standard doses of peg-IFN/RBV. The trial is a multicenter, partially double-blind, randomized, placebo-controlled trial that aims to enroll approximately 200 patients in multiple countries.

The study will measure the safety and tolerability of MK-7009 at all dose regimens as compared to placebo through 48 weeks. Additionally, the study will evaluate the proportion of patients in the MK-7009 600 mg treatment regimens achieving sustained viral response, i.e., undetectable viral load 24 weeks after the end of all study therapy, as compared to patients in the placebo regimen.

Source
Merck & Co., Inc.

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