Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION) (FUSION)

A Phase 3, Multicenter, Randomized, Double-Blind, Study to Investigate the Efficacy and Safety of GS-7977 + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

This study was to assess the safety and efficacy of sofosbuvir in combination with ribavirin (RBV) administered for 12 or 16 weeks in participants with genotypes 2 or 3 hepatitis C virus (HCV) infection as assessed by the proportion of participants with sustained virologic response (SVR) 12 weeks after discontinuation of therapy (SVR12).

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C
• Intervention / Treatment: Drug: SOF; Drug: RBV; Drug: Placebo to match SOF; Drug: Placebo to match RBV

• Study Type: Interventional
• Enrollment (Actual): 202
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 4Z6
      • University of Calgary
    • Edmonton, Alberta, Canada, T6G 2X8
      • University of Alberta Hospital
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • British Columbia
    • Vancouver, British Columbia, Canada, V5Z 1M9
      • Gordon & Leslie Diamond Health Care Centre
    • Vancouver, British Columbia, Canada, V6Z 2C9
      • University of British Columbia
    • Vancouver, British Columbia, Canada, V6Z 2K5
      • (G.I.R.I.) Gastrointestinal Research Institute
  • Manitoba
    • Winnipeg, Manitoba, Canada, R3E 3P4
      • University of Manitoba Health Sciences Center
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital
    • Toronto, Ontario, Canada, M5T 2S8
      • Toronto Western Hospital
    • Toronto, Ontario, Canada, M6H 3M1
      • Toronto Liver Centre
    • Toronto, Ontario, Canada, M5G 1X5
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 3J4
      • Hopital St. Luc
• New Zealand
  • Auckland, New Zealand, 1640
    • Auckland Clinical Studies Limited
  • Christchurch, New Zealand, 8011
    • Christchurch Hospital
• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion De Investigacion de Diego
  • San Juan, Puerto Rico, 00909-1711
    • Clinical Research Puerto Rico Inc
• United States
  • California
    • Coronado, California, United States, 92118
      • Scti Research Foundation
    • Los Angeles, California, United States, 90027
      • Kaiser Permanente
    • Los Angeles, California, United States, 90036
      • Peter J. Ruane, MD, Inc.
    • Los Angeles, California, United States, 90069
      • Anthony Mills MD, Inc.
    • San Diego, California, United States, 92123
      • Medical Associates Research Group, Inc.
    • San Diego, California, United States, 92103
      • UCSD Antiviral Research Center
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Francisco, California, United States, 94115
      • Quest Clinical Research
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado
    • Englewood, Colorado, United States, 80113
      • South Denver Gastroenterology, PC
  • District of Columbia
    • Washington, District of Columbia, United States, 20009
      • Whitman Walker Clinic
  • Florida
    • Gainesville, Florida, United States, 32610-0277
      • University of Florida
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic Baptist
    • Miami, Florida, United States, 33136
      • University of Miami
    • New Port Richey, Florida, United States, 34653
      • Advanced Research Institute
    • Orlando, Florida, United States, 32806
      • Internal Medicine Specialists
    • Orlando, Florida, United States, 32803-1851
      • Orlando Immunology Center (ACH)
    • Wellington, Florida, United States, 33414
      • South Florida Center of Gastroenterology, P.A.
  • Georgia
    • Atlanta, Georgia, United States, 30309
      • Digestive Healthcare of Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia, PC
  • Indiana
    • Indianapolis, Indiana, United States, 46237
      • Indianapolis Gastroenterology Research Foundation
  • Kentucky
    • Bowling Green, Kentucky, United States, 42101
      • Graves-Gilbert Clinic
  • Louisiana
    • Baton Rouge, Louisiana, United States, 70809
      • Gastroenterology Associates, LLC
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114-2696
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
    • Springfield, Massachusetts, United States, 01105
      • The Research Institute
  • Michigan
    • Novi, Michigan, United States, 48377
      • Henry Ford Health System
  • Minnesota
    • Minneapolis, Minnesota, United States, 55414
      • Minnesota Gastroenterology, P.A.
  • Missouri
    • Kansas City, Missouri, United States, 64131
      • Kansas City Gastroenterology and Hepatology
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Comprehensive Clinical Research
    • Hillsborough, New Jersey, United States, 08844
      • ID Care
  • New Mexico
    • Santa Fe, New Mexico, United States, 87505
      • Southwest C.A.R.E. Center
  • New York
    • Binghamton, New York, United States, 13903
      • Binghamton Gastroenterology Associates
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • North Carolina
    • Asheville, North Carolina, United States, 28801
      • Asheville Gastroenterology Associates, P.A.
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
    • Winston-Salem, North Carolina, United States, 27103
      • Digestive Health Specialists, PA
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
  • Rhode Island
    • Providence, Rhode Island, United States, 02906
      • The Miriam Hospital
    • Providence, Rhode Island, United States, 02905
      • University Gastroenterology
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Nashville, Tennessee, United States, 37211
      • Nashville Gastrointestinal Specialists, Inc
  • Texas
    • Arlington, Texas, United States, 76012
      • Texas Clinical Research Institute, LLC
    • Dallas, Texas, United States, 75219
      • Southwest Infectious Disease Clinical Research, Inc.
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Metropolitan Research
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital Center for Liver Diseases
    • Norfolk, Virginia, United States, 23502
      • Digestive and Liver Disease Specialists
    • Richmond, Virginia, United States, 23226
      • Bon Secours St. Mary's Hospital of Richmond, Inc.
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Infection with HCV genotype 2 or 3
• Had cirrhosis determination
• Prior treatment failure
• Screening laboratory values within defined thresholds
• Subject had not been treated with any investigational drug or device within 30 days of the screening visit
• Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase
• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• History of clinically significant illness or any other major medical disorder that may have interfered with subject treatment, assessment or compliance with the protocol
• Excessive alcohol ingestion or significant drug abuse

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SOF+RBV+placebo; Participants were randomized to receive SOF+RBV for 12 weeks followed by placebo to match SOF plus placebo to match RBV for 4 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet was administered orally once daily.; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Ribavirin (RBV) tablets was administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).; Drug: Placebo to match SOF; Placebo to match SOF was administered orally once daily.; Drug: Placebo to match RBV; Placebo to match RBV was administered orally twice daily.
Experimental: SOF+RBV; Participants were randomized to receive SOF+RBV for 16 weeks.	Drug: SOF; Sofosbuvir (SOF) 400 mg tablet was administered orally once daily.; Other Names: Sovaldi®; GS-7977; PSI-7977; Drug: RBV; Ribavirin (RBV) tablets was administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving SVR12	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).	Posttreatment Week 12
Adverse Events Leading to Permanent Discontinuation of Study Drug	Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment.	Baseline to Week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving SVR4	SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).	Posttreatment Week 4
Percentage of Participants Achieving SVR24	SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).	Posttreatment Week 24
Percentage of Participants With Viral Breakthrough	Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values. For the purposes of this efficacy analysis, assessments were made during active treatment (up to Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).	Up to 16 weeks
Percentage of Participants With Viral Relapse	Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement. For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).	End of treatment to posttreatment Week 24

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General Publications

• Younossi ZM, Stepanova M, Sulkowski M, Naggie S, Puoti M, Orkin C, Hunt SL. Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes. J Infect Dis. 2015 Aug 1;212(3):367-77. doi: 10.1093/infdis/jiv005. Epub 2015 Jan 12.
• Stepanova M, Nader F, Cure S, Bourhis F, Hunt S, Younossi ZM. Patients' preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens. Aliment Pharmacol Ther. 2014 Sep;40(6):676-85. doi: 10.1111/apt.12880. Epub 2014 Jul 15.
• Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, Nelson DR; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: May 21, 2012
• First Submitted That Met QC Criteria: May 22, 2012
• First Posted (Estimate): May 24, 2012

Study Record Updates

• Last Update Posted (Estimate): May 28, 2014
• Last Update Submitted That Met QC Criteria: May 9, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: HCV; Treatment Experienced; Sustained Virologic Response; Combination Therapy; Ribavirin; Direct Acting Antiviral; GS-7977; HCV genotype 3 (GT-3); HCV genotype 2 (GT-2)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir
• Other Study ID Numbers: GS-US-334-0108