Elsevier

Journal of Hepatology

Volume 64, Issue 1, January 2016, Pages 19-28
Journal of Hepatology

Research Article
Efficacy and safety of ombitasvir/paritaprevir/r and dasabuvir compared to IFN-containing regimens in genotype 1 HCV patients: The MALACHITE-I/II trials

https://doi.org/10.1016/j.jhep.2015.08.015Get rights and content
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Background & Aims

Telaprevir plus pegylated interferon/ribavirin (TPV + PegIFN/RBV) remains a therapeutic option for chronic hepatitis C virus (HCV) genotype (GT) 1 infection in many regions. We conducted two open-label, phase IIIb trials comparing safety and efficacy of all-oral ombitasvir/paritaprevir/ritonavir and dasabuvir ± ribavirin (OBV/PTV/r + DSV ± RBV) and TPV + PegIFN/RBV.

Methods

Treatment-naïve (MALACHITE-I) or PegIFN/RBV-experienced (MALACHITE-II) non-cirrhotic, chronic HCV GT1-infected patients were randomized to OBV/PTV/r + DSV + weight-based RBV, OBV/PTV/r + DSV (treatment-naïve, GT1b-infected patients only), or 12 weeks of TPV + PegIFN + weight-based RBV and 12–36 additional weeks of PegIFN/RBV. The primary endpoint was sustained virologic response 12 weeks post-treatment (SVR12). Patient-reported outcome questionnaires evaluated mental and physical health during the studies.

Results

Three hundred eleven treatment-naïve and 148 treatment-experienced patients were randomized and dosed. Among treatment-naïve patients, SVR12 rates were 97% (67/69) and 82% (28/34), respectively, in OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV-treated GT1a-infected patients; SVR12 rates were 99% (83/84), 98% (81/83), and 78% (32/41) in OBV/PTV/r + DSV + RBV, OBV/PTV/r + DSV, and TPV + PegIFN/RBV-treated GT1b-infected patients. Among treatment-experienced patients, SVR12 rates were 99% (100/101) and 66% (31/47) with OBV/PTV/r + DSV + RBV and TPV + PegIFN/RBV. Mental and physical health were generally better with OBV/PTV/r + DSV ± RBV than TPV + PegIFN/RBV. Rates of discontinuation due to adverse events (0–1% and 8–11%, respectively, p <0.05) and rates of hemoglobin decline to <10 g/dl (0–4% and 34–47%, respectively, p <0.05) were lower for OBV/PTV/r + DSV ± RBV than TPV + PegIFN/RBV.

Conclusions

Among non-cirrhotic, HCV GT1-infected patients, SVR12 rates were 97–99% with 12 week, multi-targeted OBV/PTV/r + DSV ± RBV regimens and 66–82% with 24–48 total weeks of TPV + PegIFN/RBV. OBV/PTV/r + DSV ± RBV was associated with a generally better mental and physical health, more favorable tolerability, and lower rates of treatment discontinuation due to adverse events.

Abbreviations

HCV
hepatitis C virus
GT
genotype
TPV
telaprevir
PegIFN
pegylated interferon
RBV
ribavirin
SVR
sustained virologic response
DAA
direct-acting antiviral agents
OBV
ombitasvir
PTV
paritaprevir
r
ritonavir
DSV
dasabuvir
IL28B
interleukin 28B
RNA
ribonucleic acid
MEMS
Medication Event Monitoring System
PCR
polymerase chain reaction
LLOQ
lower limit of quantitation
SF-36v2
Short Form–36 version 2 Health Survey
PRO
patient-reported outcome
MCS
mental component summary
PCS
physical component summary
WPAI-HCV
work productivity and impairment questionnaire specific for HCV
ANCOVA
analysis of covariance
CI
confidence interval
OATP
organic anion-transporting polypeptide

Keywords

Hepatitis C virus
Telaprevir
Interferon-free therapy
Direct-acting antivirals
Sustained virologic response

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These authors contributed equally to this work.