Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

Abstract

Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group.

Trial registration: ClinicalTrials.gov NCT00803309.

Conflict of interest statement

Competing Interests: B. H.: Nothing to disclose. H.-J. C.: Nothing to disclose. H. K.: Advisory Committees or Review Panels: Bristol-Myers Squibb, Merck Sharp & Dohme, Abbott, ViiV, Janssen, Boehringer, Hexal; Grant/Research Support: Gilead, Abbott, Roche, Janssen, Novartis, Bristol-Myers Squibb, Boehringer; Speaking and Teaching: Roche, Gilead, Bristol-Myers Squibb, Novartis, ViiV, Merck Sharp & Dohme. B. M.: Nothing to disclose. U. N.: Speaking and Teaching: MSD, Roche, BMS, Abbott, VIIV, Janssen. M. R.: Nothing to disclose. Michael R. R. Kraus - Advisory Committees or Review Panels: Schering-Plough, Roche; Consulting: Schering-Plough, Roche. K. H. B.: Speaking and Teaching: MSD, Roche, Janssen, Gilead, BMS, Falk Foundation, Novartis. C. R.: Nothing to disclose. M. S.: Advisory Committees or Review Panels: Roche, BMS, Norgine, Boehringer; Speaking and Teaching: Gilead, Merck, Falk. A. S.: Board Membership: MSD, Böhringer Ingelheim; Speaking and Teaching: Janssen, MSD, Gilead, Abbvie, Böhringer Ingelheim. A. T.: Advisory Committees or Review Panels: Abbott, BMS, Boehringer, GSK, MSD / Essex; Grant/Research Support: Abbott, GSK; Speaking and Teaching: Abbott, BMS, Boehringer, Gilead, GSK, MSD / Essex, Roche, ViiV. S. H.: Nothing to disclose. A. G.: Nothing to disclose. A. K.: Nothing to disclose. H. W.: Advisory Committees or Review Panels: Transgene, MSD, Roche, Gilead, Abbott, BMS, Falk; Grant/Research Support: MSD, Novartis, Gilead, Roche, Abbott; Speaking and Teaching: BMS, MSD, Novartis, ITF. M. P. M.: Consulting: Roche, BMS, Gilead, Boehringer Ingelheim, Novartis, Idenix, Achillion, GSK, Merck/MSD, Janssen, Medgenics; Grant/Research Support: Merck/MSD, Roche, Gilead, Novartis, Boehringer Ingelheim, BMS; Speaking and Teaching: Merck/MSD, Roche, BMS, Gilead, Janssen, GSK, Novartis. M. C.: Advisory Committees or Review Panels: Merck (MSD Germany), Roche, Gilead, Novartis; Grant/Research Support: Merck (MSD Germany), Roche; Speaking and Teaching: Merck (MSD Germany), Roche, Gilead, BMS, Novartis, Falk. The disclosures made by the authors do not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

Figures

Fig 1. Study design of the OPTEX 2/3 trial.

Fig 2. CONSORT flowchart for the OPTEX trial.

Fig 3. Flow chart of patients recruited for the OPTEX trial.

Fig 4. Virological response rates at EOT, FU12 and FU24 in the ITT, mITT and completer population.

Fig 5. Virological breakthrough and relapse rates in treatment Group A and B in different populations.

Fig 6. Results of SF-36 questionnaires analysing quality of life during the study period.