Sustained Virologic Response Rates from a Randomized Trial of HCV Genotype-1 Subjects Treated with Either Consensus IFN and Ribavirin or Pegylated Interferon alfa-2b and Ribavirin

It is well known that greater than 50% of HCV genotype 1 individuals treated with the standard of care, peginterferon alfa plus ribavirin, fail to achieve a sustained virological response (SVR).

Results of a few studies suggest that consensus interferon (CIFN) (Infergen) in combination with ribavirin (RBV) may be particularly active against HCV genotype 1 and therefore might improve SVR rates in this patient population.

In the current study, researchers at multiple US medical centers sought to evaluate the effects of treatment with  Proof of concept study to compare treatment with CIFN/RBV to pegylated interferon (PEGIFN) and RBV in achieving SVR.

In this prospective, randomized clinical trial, treatment-naïve HCV genotype-1 patients received either CIFN 15 mcg TIW and weight-based generic ribavirin (Ribasphere) (group 1) or PEG-Intron 1.5 mcg/kg/week and weight based ribavirin (Rebetol), (group 2).

Fifty-nine individuals were enrolled, 30 in group 1 and 29 in group 2.

Treatment lasted 48 weeks if HCV RNA was undetectable at week 24, otherwise drugs were discontinued. SVR was determined at week 72.

Safety laboratory tests and adverse events (AE) assessments were performed monthly. To date all subjects have completed week 48 and 56 subjects have finished week 72.

Results

- At baseline the 2 groups were similar in gender (67% men), age (mean = 44 years), weight (202 lbs men, 152 lbs women), ethnicity (59% Caucasian, 30% African American), high viral load (75%, mean levels:  3.8 and 3.6 million IU/mL for groups 1 and 2) and hemoglobin (mean: 15 g/dL).

- Cirrhosis was diagnosed in 3 subjects in group 1 and 5 subjects in group 2. The SVR was similar for both groups: 37% for CIFN/RBV and 35% for PEGIFN/RBV.

- No subject dropped hemoglobin to <8.5 g/dL. Neutrophils dropped to <750/uL in 13% and 24% of groups 1 and 2, respectively (p= 0.29).

- Dose modification for one or two drugs were required in 37% and 62% in each of the 2 groups (p=0.09).

- AE were flu-like symptoms in 100% and 93%, headache in 63% and 39%, fatigue in 77% and 50%, mood disorders in 67% and 66%.

- Serious AE were observed in 6 subjects (3 per group) (cellulitis, severe fatigue, psychosis, seizure, dehydration, EtOH recidivism, and pyelonephritis).

Based on these results, the study authors conclude, “CIFN/RBV combination therapy elicited a comparable SVR to PEGIFN/RBV in previously untreated subjects with genotype-1 chronic HCV.”

“There were no relapsers among the CIFN/RBV treated group.”

“The AE profile for CIFN/RBV demonstrated less neutropenia and dose reductions.”

“A larger clinical trial for genotype-1 chronic HCV infection utilizing CIFN and ribavirin is warranted.

11/28/05

Reference
M Sjogren and others. Sustained Virologic Response Rates from a Randomized Trial of HCV Genotype-1 Subjects Treated with Either Consensus IFN and Ribavirin or Pegylated Interferon alfa-2b and Ribavirin. Abstract 851. 56th annual meeting of the American Association for the Study of Liver Diseases. November 11-15, 2005. San Francisco, CA.