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Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients.
Ann Hepatol. 2012 Jan-Feb; 11(1):15-31.AH

Abstract

INTRODUCTION

Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin.

MATERIAL AND METHODS

Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns.

RESULTS

The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication.

CONCLUSION

Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439).

Authors+Show Affiliations

Division of Gastroenterology, Hepatology, and Nutrition, University of Florida, Gainsville, USA. nelsodr@medicine.ufl.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22166557

Citation

Nelson, David R., et al. "Balapiravir Plus Peginterferon Alfa-2a (40KD)/ribavirin in a Randomized Trial of Hepatitis C Genotype 1 Patients." Annals of Hepatology, vol. 11, no. 1, 2012, pp. 15-31.
Nelson DR, Zeuzem S, Andreone P, et al. Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients. Ann Hepatol. 2012;11(1):15-31.
Nelson, D. R., Zeuzem, S., Andreone, P., Ferenci, P., Herring, R., Jensen, D. M., Marcellin, P., Pockros, P. J., Rodríguez-Torres, M., Rossaro, L., Rustgi, V. K., Sepe, T., Sulkowski, M., Thomason, I. R., Yoshida, E. M., Chan, A., & Hill, G. (2012). Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients. Annals of Hepatology, 11(1), 15-31.
Nelson DR, et al. Balapiravir Plus Peginterferon Alfa-2a (40KD)/ribavirin in a Randomized Trial of Hepatitis C Genotype 1 Patients. Ann Hepatol. 2012;11(1):15-31. PubMed PMID: 22166557.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients. AU - Nelson,David R, AU - Zeuzem,Stefan, AU - Andreone,Pietro, AU - Ferenci,Peter, AU - Herring,Robert, AU - Jensen,Donald M, AU - Marcellin,Patrick, AU - Pockros,Paul J, AU - Rodríguez-Torres,Maribel, AU - Rossaro,Lorenzo, AU - Rustgi,Vinod K, AU - Sepe,Thomas, AU - Sulkowski,Mark, AU - Thomason,Isaac R, AU - Yoshida,Eric M, AU - Chan,Anna, AU - Hill,George, PY - 2011/12/15/entrez PY - 2011/12/15/pubmed PY - 2012/6/13/medline SP - 15 EP - 31 JF - Annals of hepatology JO - Ann Hepatol VL - 11 IS - 1 N2 - INTRODUCTION: Balapiravir (R1626, RG1626) is the prodrug of a nucleoside analogue inhibitor of the hepatitis C virus (HCV) RNA-dependent RNA polymerase (R1479, RG1479). This phase 2, double-blind international trial evaluated the optimal treatment regimen of balapiravir plus peginterferon alfa-2a (40KD)/ribavirin. MATERIAL AND METHODS: Treatment-naive genotype 1 patients (N = 516) were randomized to one of seven treatment groups in which they received balapiravir 500, 1,000, or 1,500 mg twice daily, peginterferon alfa-2a (40KD) 180 or 90 µg/week and ribavirin 1,000/1,200 mg/day or peginterferon alfa-2a (40KD)/ribavirin. The planned treatment duration with balapiravir was reduced from 24 to 12 weeks due to safety concerns. RESULTS: The percentage of patients with undetectable HCV RNA was consistently higher in all balapiravir groups from week 2 to 12. However, high rates of dose modifications and discontinuations of one/all study drugs compromised the efficacy assessment and resulted in similar sustained virological response rates in the balapiravir groups (range 32-50%) and the peginterferon alfa-2a (40KD)/ribavirin group (43%). Balapiravir was discontinued for safety reasons in 28-36% of patients (most often for lymphopenia) and the percentage of patients with serious adverse events (especially hematological, infection, ocular events) was dose related. Serious hematological adverse events (particularly neutropenia, lymphopenia) were more common in balapiravir recipients. Two deaths in the balapiravir/peginterferon alfa-2a/ribavirin combination groups were considered possibly related to study medication. CONCLUSION: Further development of balapiravir for the treatment of chronic hepatitis C has been halted because of the unacceptable benefit to risk ratio revealed in this study (www.ClinicalTrials.gov NCT 00517439). SN - 1665-2681 UR - https://www.unboundmedicine.com/medline/citation/22166557/Balapiravir_plus_peginterferon_alfa_2a__40KD_/ribavirin_in_a_randomized_trial_of_hepatitis_C_genotype_1_patients_ L2 - https://linkinghub.elsevier.com/retrieve/pii/968763 DB - PRIME DP - Unbound Medicine ER -