TY  - JOUR
A1  - Nelson, David R.
A1  - Zeuzem, Stefan
A1  - Andreone, Pietro
A1  - Ferenci, Peter
A1  - Herring, Robert
A1  - Jensen, Donald M.
A1  - Marcellin, Patrick
A1  - Pockros, Paul J.
A1  - Rodríguez-Torres, Maribel
A1  - Rossaro, Lorenzo
A1  - Rustgi, Vinod K.
A1  - Sepe, Thomas
A1  - Sulkowski, Mark
A1  - Thomason, Isaac R.
A1  - Yoshida, Eric M.
A1  - Chan, Anna
A1  - Hill, George
T1  - Balapiravir plus peginterferon alfa-2a (40KD)/ribavirin in a randomized trial of hepatitis C genotype 1 patients
T2  - Annals of hepatology
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 alfa2a (40KD) 180 or 90 Mg/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).
KW  - Chronic hepatitis C
KW  - SVR
KW  - Safety
Y1  - 2019
UR  - http://publikationen.ub.uni-frankfurt.de/frontdoor/index/index/docId/76745
UR  - https://nbn-resolving.org/urn:nbn:de:hebis:30:3-767453
SN  - 1665-2681
VL  - 11
IS  - 1
SP  - 15
EP  - 31
PB  - Mexican Association of Hepatology
CY  - México
ER  -