Abstract
Background:
Effective treatment options are needed for patients with genotype 1 or 3 hepatitis C virus (HCV) infection in whom previous therapy has failed.
Objective:
To assess the efficacy and safety of sofosbuvir plus velpatasvir, with and without ribavirin, in treatment-experienced patients.
Design:
Randomized, phase 2, open-label study. (ClinicalTrials.gov: NCT01909804)
Setting:
58 sites in Australia, New Zealand, and the United States.
Patients:
Treatment-experienced adults with genotype 3 HCV infection without cirrhosis (cohort 1) and with compensated cirrhosis (cohort 2) and patients with genotype 1 HCV infection that was unsuccessfully treated with a protease inhibitor with peginterferon and ribavirin (50% could have compensated cirrhosis) (cohort 3).
Intervention:
All patients received 12 weeks of treatment that included 400 mg of sofosbuvir once daily. Patients in each cohort were randomly assigned to 25 mg of velpatasvir once daily with or without ribavirin or 100 mg of velpatasvir once daily with or without ribavirin.
Measurements:
Proportion of patients with sustained virologic response at week 12 after treatment (SVR12).
Results:
In cohort 1, SVR12 rates were 85% with 25 mg of velpatasvir, 96% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 100% with 100 mg of velpatasvir plus ribavirin. In cohort 2, SVR12 rates were 58% with 25 mg of velpatasvir, 84% with 25 mg of velpatasvir plus ribavirin, 88% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. In cohort 3, SVR12 rates were 100% with 25 mg of velpatasvir, 97% with 25 mg of velpatasvir plus ribavirin, 100% with 100 mg of velpatasvir, and 96% with 100 mg of velpatasvir plus ribavirin. The most common adverse events were headache, fatigue, and nausea.
Limitation:
Treatment assignments were not blinded, and no inferential statistics were planned.
Conclusion:
Treatment with 400 mg of sofosbuvir plus 100 mg of velpatasvir for 12 weeks was well-tolerated and highly effective in treatment-experienced patients with genotype 1 or 3 HCV infection.
Primary Funding Source:
Gilead Sciences.
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Author, Article, and Disclosure Information
Stephen Pianko,
From Monash Health and Monash University, Clayton, Victoria, Australia; Northwestern University, Chicago, Illinois; Liver Institute of Virginia, Richmond, Virginia; Weill Cornell Medical College, New York, New York; Royal Prince Alfred Hospital and University of Sydney, Camperdown, New South Wales, Australia; Kirby Institute, University of New South Wales, and St. Vincent's Hospital, Sydney, New South Wales, Australia; Gilead Sciences, Foster City, California;
University of Pittsburgh, Pittsburgh, Pennsylvania; Kaiser Permanente Medical Center, Los Angeles, California; Auckland Clinical Studies, Auckland, New Zealand; Christchurch Clinical Studies Trust and University of Otago, Christchurch, New Zealand; University of Pennsylvania, Philadelphia, Pennsylvania; and Alfred Health and Monash University, Melbourne, Victoria, Australia.
Acknowledgment: The authors thank the staff and patients who participated in the study. Laila Guzadhur, PhD, from Niche Science and Technology (Richmond-Upon-Thames, London, United Kingdom), provided writing and editorial support during development of this manuscript (these services were paid for by Gilead Sciences). Editorial assistance was provided by David McNeel of Gilead Sciences.
Grant Support: By Gilead Sciences.
Disclosures: Dr. Pianko reports personal fees from Gilead Sciences, Roche Diagnostics, and AbbVie during the conduct of the study; other from Gilead Sciences, Bristol-Myers Squibb, AbbVie, and Merck during the conduct of the study; and personal fees and nonfinancial support from Gilead Sciences outside the submitted work. Dr. Flamm reports personal fees from Gilead Sciences, Bristol-Myers Squibb, AbbVie, Janssen Pharmaceuticals, and Merck and grants from Gilead Sciences, Bristol-Myers Squibb, AbbVie, and Janssen Pharmaceuticals outside the submitted work. Dr. Shiffman reports grants from Gilead Sciences during the conduct of the study; grants from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Conatus, Galectin, Gilead Sciences, Intercept, Lumena, and Merck outside the submitted work; and personal fees from AbbVie, Bristol-Myers Squibb, Boehringer Ingelheim, Gilead Sciences, Janssen Pharmaceuticals, and Merck outside the submitted work. Dr. Kumar reports personal fees from Gilead Sciences outside the submitted work. Dr. Strasser reports personal fees from Gilead Sciences outside the submitted work. Dr. Dore reports grants from AbbVie, Merck, Bristol-Myers Squibb, Janssen Pharmaceuticals, and Roche Diagnostics; personal fees from Gilead Sciences, AbbVie, Merck, Bristol-Myers Squibb, Janssen Pharmaceuticals, Roche Diagnostics, and GlaxoSmithKline; and nonfinancial support from Gilead, AbbVie, Merck, Bristol-Myers Squibb, and Roche Diagnostics outside the submitted work. Dr. McNally is an employee and stockholder of Gilead Sciences. Dr. Brainard reports other from Gilead Sciences outside the submitted work. Dr. Doehle reports personal fees from Gilead Sciences during the conduct of the study. Dr. Mogalian reports other from Gilead Sciences during the conduct of the study. Dr. McHutchison reports other from Gilead Sciences during the conduct of the study. Dr. Towner reports grants from Gilead during the conduct of the study and grants from Bristol-Myers Squibb, ViiV, and Merck outside the submitted work. Dr. Gane reports personal fees from Gilead Speakers Bureau and Gilead Advisors' Meeting outside the submitted work. Dr. Stedman reports nonfinancial support from Gilead Sciences during the conduct of the study and personal fees and nonfinancial support from Gilead Sciences, AbbVie, and Merck outside the submitted work. Dr. Reddy reports grants and personal fees from Gilead Sciences during the conduct of the study; personal fees from AbbVie, Merck, Janssen Pharmaceuticals, Gilead Sciences, Bristol-Myers Squibb, UpToDate, and ViralEd outside the submitted work; grants from AbbVie, Merck, Janssen Pharmaceuticals, and Bristol-Myers Squibb outside the submitted work. Dr. Roberts reports other from Gilead Sciences, Bristol-Myers Squibb, Merck, and AbbVie outside the submitted work. Authors not named here have disclosed no conflicts of interest. Forms can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M15-1014.
Editors' Disclosures: Christine Laine, MD, MPH, Editor in Chief, reports that she has no financial relationships or interests to disclose. Darren B. Taichman, MD, PhD, Executive Deputy Editor, reports that he has no financial relationships or interests to disclose. Cynthia D. Mulrow, MD, MSc, Senior Deputy Editor, reports that she has no relationships or interests to disclose. Deborah Cotton, MD, MPH, Deputy Editor, reports that she has no financial relationships or interest to disclose. Jaya K. Rao, MD, MHS, Deputy Editor, reports that she has stock holdings/options in Eli Lilly and Pfizer. Sankey V. Williams, MD, Deputy Editor, reports that he has no financial relationships or interests to disclose. Catharine B. Stack, PhD, MS, Deputy Editor for Statistics, reports that she has stock holdings in Pfizer.
Reproducible Research Statement:Study protocol: See Supplement. Statistical code and data set: Not available.
Corresponding Author: Stephen Pianko, MD, PhD, Monash Health, 10 Ancora Imparo Way, Monash University, Victoria 3800 Australia; e-mail, spianko@geds.
Current Author Addresses: Dr. Pianko: Monash Health, 10 Ancora Imparo Way, Monash University, Victoria 3800, Australia.
Dr. Flamm: Kovler Organ Transplantation Center, 676 North St. Clair Street, Suite 1900, Chicago, IL 60611.
Dr. Shiffman: Liver Institute of Virginia, Bon Secours Health System, 5855 Bremo Road, Suite 509, Richmond, VA 23226.
Dr. Kumar: Director of Clinical Hepatology, Assistant Professor of Medicine, Division of Gastroenterology and Hepatology, Weill Cornell Medical College, 1305 York Avenue, 4th Floor, New York, NY 10021.
Dr. Strasser: University of Sydney, AW Morrow Gastroenterology and Liver Centre, Royal Prince Alfred Hospital, Missenden Road, Camperdown, North South Wales 2050, Australia.
Dr. Dore: Head, Viral Hepatitis Clinical Research Program, Kirby Institute, University of North South Wales Australia, Wallace Wurth Building, Sydney, North South Wales 2052 Australia.
Drs. McNally, Brainard, Han, Doehle, Mogalian, and McHutchison: Gilead Sciences, 333 Lakeside Drive, Foster City, CA 94404.
Dr. Rabinovitz: Professor of Medicine, Division of Gastroenterology and Hepatology, University of Pittsburgh, Kaufmann Building, 3471 Fifth Avenue, Suite 916, Pittsburgh, PA 15213.
Dr. Towner: Department of Infectious Diseases, Kaiser Permanente Los Angeles Medical Center, 1505 North Edgemont Street, Los Angeles, CA 90027.
Dr. Gane: New Zealand Liver Transplant Unit, Level 15 Support Building, Auckland City Hospital, Park Road, Auckland 1142, New Zealand.
Dr. Stedman: Christchurch Clinical Studies and University of Otago, Christchurch, Riccarton Avenue, Christchurch 8011, New Zealand.
Dr. Reddy: Viral Hepatitis Center, University of Pennsylvania, 2 Dulles, Liver Transplant Office, 3400 Spruce Street, Philadelphia, PA 19104.
Dr. Roberts: Department of Gastroenterology, Alfred Health, 99 Commercial Road, PO Box 315 Prahran, Victoria 3181, Australia.
Author Contributions: Conception and design: J. McNally, D.M. Brainard, E. Mogalian, J.G. McHutchison.
Analysis and interpretation of the data: S. Pianko, M.L. Shiffman, S.I. Strasser, G.J. Dore, J. McNally, D.M. Brainard, L. Han, B. Doehle, E. Mogalian, E.J. Gane, S.K. Roberts.
Drafting of the article: S. Pianko, J. McNally, W.J. Towner, S.K. Roberts.
Critical revision of the article for important intellectual content: S. Pianko, S.L. Flamm, S. Kumar, S.I. Strasser, D.M. Brainard, B. Doehle, M. Rabinovitz, W.J. Towner, E.J. Gane, C.A.M. Stedman, K.R. Reddy, S.K. Roberts.
Final approval of the article: S. Pianko, S.L. Flamm, M.L. Shiffman, S. Kumar, S.I. Strasser, G.J. Dore, J. McNally, D.M. Brainard, L. Han, B. Doehle, E. Mogalian, J.G. McHutchison, M. Rabinovitz, W.J. Towner, E.J. Gane, C.A.M. Stedman, K. Rajender Reddy, S.K. Roberts.
Provision of study materials or patients: S. Pianko, M.L. Shiffman, S.I. Strasser, G.J. Dore, W.J. Towner, C.A.M. Stedman, S.K. Roberts.
Statistical expertise: L. Han.
Collection and assembly of data: S. Pianko, M.L. Shiffman, G.J. Dore, J. McNally, E. Mogalian, M. Rabinovitz, E.J. Gane, C.A.M. Stedman.
This article was published online first at www.annals.org on 10 November 2015.
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