• Viral Infections Liver Conditions
• Hepatology Clinical Trials

• Viral Infections
• Hepatology
• Liver Conditions
• Hepatology Clinical Trials

ACH-3102 is a second-generation hepatitis C virus (HCV) nonstructural 5A (NS5A) protein inhibitor with potent activity against HCV genotype (GT)-1 through GT-6 [Zhao et al. EASL. 2012; Yang et al. AASLD. 2011]. ACH-3102 retains activity against multiple HCV variants resistant to first-generation NS5A inhibitors [Nakamoto S et al. World J Gastroenterol. 2014; Gao M. Curr Opin Virol. 2013; Zhao et al. EASL. 2012; Yang et al. AASLD. 2011]. ACH-3422, an HCV nonstructural 5B (NS5B) uridine nucleotide polymerase inhibitor, is under development for use in combination with ACH-3102.

Edward J. Gane, MD, Auckland Hospital, Auckland, New Zealand, presented interim results of an ongoing phase 2 open-label study of ACH-3102 plus sofosbuvir, which was used as a proxy for ACH-3422. Sofosbuvir is an HCV NS5B uridine nucleotide polymerase inhibitor that has been studied in multiple clinical trials in combination with NS5A inhibitors [Feeney ER and Chung RT. BMJ. 2014]. The objective of this study was to evaluate the safety and efficacy of 8 and 6 weeks of ACH-3102 plus sofosbuvir therapy in treatment-naïve patients with chronic HCV GT-1 infection.

Two cohorts of patients were enrolled. In Cohort 1, patients were randomized to receive ACH-3102 plus sofosbuvir for 8 weeks (n = 12) or observation without treatment for 12 weeks (n = 6). Sustained viral response 4 (SVR4) results were obtained before proceeding with Cohort 2. Cohort 2 included the 6 observational patients from Cohort 1 plus 12 newly randomized patients. The 6 Cohort 1 observational patients were assigned to ACH-3102 plus sofosbuvir for 6 weeks. The additional 12 patients were randomized to ACH-3102 plus sofosbuvir for 6 weeks (n = 6) or observation for 10 weeks (n = 6).

The primary end point was SVR at 12 weeks after treatment ended (SVR12) in patients who received 8 or 6 weeks of ACH-3102 plus sofosbuvir. The secondary end points included SVR4, SVR8, rapid virologic response (RVR), end-of-treatment response (ETR), and adverse event (AE) rates.

In Cohort 1, all 12 patients treated with ACH-3102 plus sofosbuvir achieved HCV RNA levels < the lower limit of quantification (LLOQ) by week 3 and < the LLOQ target not detected (LLOQ_TND) by week 5. Among patients who received 8 weeks of active treatment, 100% achieved ETR, SVR4, SVR8, and SVR12, and 83% achieved RVR. To date, 5 Cohort 2 patients who received active treatment have achieved ETR. Eight patients who completed 4 weeks of treatment have achieved HCV RNA < LLOQ.

Table 1 shows the treatment-emergent AEs occurring in > 10% of Cohort 1 patients.

Combination therapy with ACH-3102 and sofosbuvir for 8 weeks achieved rapid sustained viral load declines with 100% SVR12. These results were observed in patients with high baseline viral loads, including 9 patients with a baseline viral load > 6 000 000 international units (IU)/ mL, 7 of whom had > 7 log₁₀ IU/mL. A rapid decline in viral load was also observed after 6 weeks of treatment. The combination treatment was well tolerated with no significant AEs, electrocardiogram findings, or laboratory abnormalities. These observations will inform future clinical trials using ACH-3102 plus ACH-3422 as an interferon- and ribavirin-free regimen for the treatment of chronic HCV infection.

• © 2014 MD Conference Express®