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Randomized Phase 3 Trial of Ombitasvir/Paritaprevir/Ritonavir and Ribavirin for Hepatitis C Virus Genotype 2-Infected Japanese Patients

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Abstract

Introduction

In Japan, hepatitis C virus (HCV) genotype (GT) 2 accounts for approximately 32% of HCV infections. Limited treatment options exist in Japan for HCV GT2-infected patients. GIFT-II was a phase 3, randomized, open-label study evaluating the efficacy and safety of 16- and 12-week regimens of co-formulated ombitasvir (OBV)/paritaprevir (PTV)/ritonavir (r) plus ribavirin (RBV) in Japanese adults with HCV GT2 infection.

Methods

Patients were randomized in a 1:1 ratio to once-daily, co-formulated OBV/PTV/r (25/150/100 mg) with weight-based RBV for 16 or 12 weeks. The primary efficacy endpoint was the sustained virologic response at 12 weeks post-treatment (SVR12) rate in the primary efficacy population of non-cirrhotic treatment-naive patients.

Results

A total of 171 patients were randomized to OBV/PTV/r + RBV. In the primary efficacy population, SVR12 rates were 91.5% (43/47; 95% confidence interval 83.5–99.5%) and 75.0% (36/48; 95% confidence interval 62.8–87.2%) in the 16-week arm and 12-week arm, respectively. No patient in the 16-week arm relapsed by post-treatment week 12. Among non-cirrhotic treatment-experienced patients, the overall SVR rate in the 16-week arm was 75.8% (25/33) and was highest [93.8% (15/16)] among those who had relapsed after previous interferon-based therapy. SVR12 rates were consistently higher in patients with HCV GT2a infection versus HCV GT2b infection [16-week treatment arm: 93.9% (31/33) versus 85.7% (12/14) and 93.8% (15/16) versus 56.3% (9/16) among non-cirrhotic treatment-naive and treatment-experienced patients, respectively]. No patient discontinued treatment because of an adverse event. The most common adverse events were anemia, increased blood bilirubin, and nasopharyngitis.

Conclusions

OBV/PTV/r + RBV for 16 weeks resulted in high SVR12 rates in non-cirrhotic Japanese patients infected with HCV GT2 who were treatment-naive or who had relapsed after an interferon-based therapy. Higher SVR12 rates were observed among patients with HCV GT2a infection versus those with GT2b infection. This regimen demonstrated a favorable safety profile.

Trial Registration: ClinicalTrials.gov identifier, NCT02023112.

Funding: AbbVie.

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Acknowledgements

AbbVie sponsored the study (NCT02023112); contributed to its design; participated in the collection, analysis, and interpretation of the data, and in the writing, reviewing, and approval of the publication. AbbVie also funded the publication charges. All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this manuscript, take responsibility for the integrity of the work as a whole, and have given final approval to the version to be published. All authors had full access to all of the data in this study and take complete responsibility for the integrity of the data and accuracy of the data analysis. Medical writing support was provided by Andrew Kerr of Medical Expressions, funded by AbbVie.

Disclosures

K. Sato received payment for lectures from MSD, AbbVie, BMS, Chugai Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Gilead, Mitsubishi Tanabe Pharma, and Janssen Pharmaceutical K.K.; received research funding from AbbVie, MSD, Sumitomo Dainippon Pharma Co., Ltd., BMS, and Mitsubishi Tanabe Pharma. K. Chayama receives payment for lectures from MSD, AbbVie, BMS, Ajinomoto Pharmaceuticals Co., Ltd., Abbott, Astellas Phama Inc., Chugai Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Gilead, Mitsubishi Tanabe Pharma; received research funding from Ajinomoto Pharmaceuticals Co., Ltd., AbbVie, MSD, EA Pharma Co., Ltd., Toray Industries, Inc., Otsuka Pharmaceutical Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Mitsubishi Tanabe Pharma, Chugai Pharmaceutical Co., Ltd., BMS, Roche Diagnostics K.K., Janssen Pharmaceutical K.K. H. Toyoda received payment for lectures from BMS, AbbVie, Gilead, Sumitomo Dainippon Pharma Co., Ltd., Abbott, Wako Pure Chemical Industries Ltd., Sysmex Corporation. F. Suzuki received payment for lectures including service on speaker bureaus: BMS. H. Kumada received payment for lectures from AbbVie, MDS, Gilead, Sumitomo Dainippon Pharma Co. Ltd, BMS, and GSK; and owns a patent with SRL, Inc. K. Alves is an employee of AbbVie and may hold stock or options. L. Rodrigues Jr is an employee of AbbVie and may hold stock or options. K. Kato is an employee of AbbVie and may hold stock or options. X. Zhang is an employee of AbbVie and may hold stock or options. C. Setze is an employee of AbbVie and may hold stock or options. T. Pilot-Matias is an employee of AbbVie and may hold stock or options. M. Burroughs is an employee of AbbVie and may hold stock or options. R. Redman is an employee of AbbVie and may hold stock or options.

Compliance with Ethics Guidelines

All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1964, as revised in 2013. Informed consent was obtained from all patients for being included in the study.

Data Availability

The datasets generated during and/or analyzed during the current study are not publicly available because of company confidentiality but are available from the corresponding author on reasonable request.

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Correspondence to Ken Sato.

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Sato, K., Chayama, K., Alves, K. et al. Randomized Phase 3 Trial of Ombitasvir/Paritaprevir/Ritonavir and Ribavirin for Hepatitis C Virus Genotype 2-Infected Japanese Patients. Adv Ther 34, 1449–1465 (2017). https://doi.org/10.1007/s12325-017-0506-y

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