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

• ClinicalTrials.gov Identifier: NCT01604850
• Recruitment Status: Completed
• First Posted: May 24, 2012
• Results First Posted: May 1, 2014
• Last Update Posted: May 28, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: May 21, 2012
• First Posted Date: May 24, 2012
• Results First Submitted Date: March 31, 2014
• Results First Posted Date: May 1, 2014
• Last Update Posted Date: May 28, 2014
• Study Start Date: June 2012
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 9, 2014)

• Percentage of Participants Achieving SVR12 [ Time Frame: Posttreatment Week 12 ]
  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).
• Adverse Events Leading to Permanent Discontinuation of Study Drug [ Time Frame: Baseline to Week 16 ]
  Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment.

Original Primary Outcome Measures (submitted: May 22, 2012)

• Efficacy 12 weeks post dosing [ Time Frame: 12 weeks ]
  The proportion of patients with a sustained virologic response (SVR) 12 weeks after the end of treatment
• The safety and tolerability of GS-7977+RBV when given for 12 or 16 weeks [ Time Frame: 12 or 16 weeks ]
  The safety and tolerability of GS-7977+RBV when given for 12 or 16 weeks as measured by review of the accumulated safety data

Current Secondary Outcome Measures (submitted: May 9, 2014)

• Percentage of Participants Achieving SVR4 [ Time Frame: Posttreatment Week 4 ]
  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).
• Percentage of Participants Achieving SVR24 [ Time Frame: Posttreatment Week 24 ]
  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).
• Percentage of Participants With Viral Breakthrough [ Time Frame: Up to 16 weeks ]
  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).
• Percentage of Participants With Viral Relapse [ Time Frame: End of treatment to posttreatment Week 24 ]
  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).

Original Secondary Outcome Measures (submitted: May 22, 2012)

• Efficacy 4 and 24 weeks post dosing [ Time Frame: 4 weeks and 24 weeks ]
  To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
• Amount of circulating HCV RNA [ Time Frame: 12 weeks post dosing ]
  To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
• Characterization of viral resistance [ Time Frame: 12 weeks ]
  To evaluate the emergence of viral resistance to GS 7977 during treatment and after treatment discontinuation

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION)
• Official Title: 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
• Brief Summary: 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).
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C

Intervention

• 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.

Study Arms

• 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.
  Interventions:

  • Drug: SOF
  • Drug: RBV
  • Drug: Placebo to match SOF
  • Drug: Placebo to match RBV
• Experimental: SOF+RBV
  Participants were randomized to receive SOF+RBV for 16 weeks.
  Interventions:

  • Drug: SOF
  • Drug: RBV

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 19, 2013): 202
• Original Estimated Enrollment (submitted: May 22, 2012): 200
• Actual Study Completion Date: May 2013
• Actual Primary Completion Date: February 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada, New Zealand, Puerto Rico, United States

Administrative Information

• NCT Number: NCT01604850
• Other Study ID Numbers: GS-US-334-0108
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Gilead Sciences
• Verification Date: May 2014