By Liz Highleyman
Xavier Forns from the University of Barcelona and an international team of colleagues conducted an open-label Phase 2 trial evaluating telaprevir in combination with the standard regimen of pegylated interferon plus ribavirin in people with hard-to-treat HCV genotype 1 who had not received prior interferon-based therapy.
Study C208 included 161 participants in several European countries. About half were men, 90% were white, the mean age was about 45 years, about 20% had advanced fibrosis or cirrhosis, and approximately 80% had high baseline HCV RNA (> 800,000 IU/mL).
Participants were randomly allocated to 4 treatment arms, receiving telaprevir at doses of either 750 mg 3 times daily (every 8 hours) or 1125 mg twice daily (every 12 hours), along with pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (PegIntron) plus weight-adjusted ribavirin. Patients took telaprevir for 12 weeks and then continued pegylated interferon/ribavirin for at least an additional 12 weeks.
In a response-guided design, patients who achieved rapid virological response (RVR) at week 4 and maintained undetectable viral load (< 25 IU/mL) through week 20 stopped treatment at 24 weeks, while those who did not meet these criteria received pegylated interferon/ribavirin for 48 weeks.
The main finding of Study C208 was that 80%-85% of patients across treatment arms achieved sustained virological response (SVR), or undetectable HCV viral load 24 weeks after completing therapy. At EASL the investigators presented data from a sub-analysis of efficacy according to dosing schedule and type of pegylated interferon.
Results
- 68% of participants had undetectable HCV RNA from week 4 through 20 and were therefore eligible to stop therapy at 24 weeks.
- 18% required treatment for 48 weeks.
- 14% discontinued treatment before week 24 due to virological failure, adverse events, or for other reasons.
Overall, in an intent-to-treat analysis, sustained response rates were high regardless of how often people took telaprevir or which type of pegylated interferon they used:
- Every 8 hours with Pegasys: 85%;
- Every 8 hours with PegIntron: 81%;
- Every 12 hours with Pegasys: 83%;
- Every 12 hours with PegIntron: 82%;
People who achieved RVR and were treated for 24 weeks did better than those without SVR who were treated for 48 weeks (96% vs 79%, respectively).
Rates of viral breakthrough during treatment and relapse after treatment completion were low (14 and 9 participants, respectively).
Rates of adverse event were similar across treatment arms.
The most common adverse events were skin rash and pruritus (itching).
8% of participants discontinued therapy due to adverse events, most often rash.
"The majority of patients (68%) qualified to receive 24 weeks of total treatment duration ([due to] undetectable HCV RNA from week 4 through week 20)," the researchers concluded.
"Among these, a high proportion (93%-100%) achieved a SVR, regardless of pegylated interferon type or telaprevir dosing schedule," they added. "Continuing pegylated interferon/ribavirin beyond 24 weeks resulted in high SVR rate in patients that did not meet criteria for shorter treatment."
Liver Unit, University of Barcelona, Barcelona, Spain; Hôpital Beaujon, Clichy, France; Department of Internal Medicine, Medical University of Vienna, Vienna, Austria; Klinikum der Universität zu Köln, Cologne, Germany; Department of Hepatology, University Hospital Gasthuisberg, Leuven, Belgium; Clinic of Infectious and Tropical Diseases, University of Brescia, Brescia, Italy; Radboud University Nijmegen Medical Center, Nijmegen; Netherlands; Hôpital St Antoine, Paris, France; Tibotec BVBA, Mechelen, Belgium; Tibotec Inc, Yardley, PA.
Source: www.hivandhepatitis.com
