Published online Feb 8, 2017. doi: 10.4254/wjh.v9.i4.217
Peer-review started: July 9, 2016
First decision: September 7, 2016
Revised: October 12, 2016
Accepted: December 13, 2016
Article in press: December 14, 2016
Published online: February 8, 2017
Processing time: 215 Days and 8.8 Hours
To evaluate efficacy/safety of hepatitis C virus (HCV) protease inhibitor boceprevir with pegylated interferon (PEG-IFN) alfa and weight-based ribavirin (RBV) in a phase 3 trial.
A prospective, multicenter, phase 3, open-label, single-arm study of PEG-IFN alfa, weight-based RBV, and boceprevir, with a PEG-IFN/RBV lead-in phase was performed. The HCV/human immunodeficiency virus coinfected study population included treatment naïve (TN) and treatment experienced (TE) patients. Treatment duration ranged from 28 to 48 wk dependent upon response-guided criteria. All patients had HCV Genotype 1 with a viral load > 10000 IU/mL. Compensated cirrhosis was allowed. Sample size was determined to establish superiority to historical (PEG-IFN plus RBV) rates in sustained viral response (SVR).
A total of 257 enrolled participants were analyzed (135 TN and 122 TE). In the TN group, 81.5% were male and 54.1% were black. In the TE group, 76.2% were male and 47.5% were white. Overall SVR12 rates (HCV RNA < lower limit of quantification, target not detected, target not detected) were 35.6% in TN and 30.3% in TE. Response rates at SVR24 were 28% in TN and 10% in TE, and exceeded those in historical controls. The highest rate was observed in TN non-cirrhotic participants (36.8% and the lowest in TE cirrhotics (26.3%). Cirrhotic TN participants had a 27.8% SVR12 rate and 32.1% of TE non-cirrhotics achieved SVR12. Significantly lower response rates were observed among black participants; in the TE, SVR12 was 39.7% in white participants but only 13.2% of black subjects (P = 0.002). Among the TN, SVR12 was 42.1% among whites and 27.4% among blacks (P = 0.09).
The trial met its hypothesis of improved SVR compared to historical controls but overall SVR rates were low. All-oral HCV treatments will mitigate these difficulties.
Core tip: Approval of first generation hepatitis C virus (HCV) protease inhibitors has initiated a change in care of HCV infected patients. Phase 2 trials in HCV/human immunodeficiency virus coinfected patients have suggested improved efficacy and tolerability for regimens that combined pegylated interferon (PEG-IFN) + ribavirin (RBV) with either boceprevir or telaprevir. We evaluated an HCV treatment regimen using a first generation HCV protease inhibitor (boceprevir) with PEG-IFN, and weight-based RBV in a phase 3 treatment trial, including HCV treatment-naïve and treatment-experienced coinfected subjects. While sustained viral response rates were low overall they did exceed historical PEG-IFN/RBV rates. Use of new interferon-free direct acting antiviral agents modalities in this population is indicated.