Phase 3 Study of Sofosbuvir and Ribavirin (FISSION)

• ClinicalTrials.gov Identifier: NCT01497366
• Recruitment Status: Completed
• First Posted: December 22, 2011
• Results First Posted: April 2, 2014
• Last Update Posted: April 2, 2014
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: December 19, 2011
• First Posted Date: December 22, 2011
• Results First Submitted Date: January 15, 2014
• Results First Posted Date: April 2, 2014
• Last Update Posted Date: April 2, 2014
• Study Start Date: December 2011
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2014)

Percentage of Participants With Sustained Virologic Response 12 Weeks After Stopping All Study Drugs (SVR12) [ Time Frame: Post-treatment Week 12 ]

SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; < 25 IU/mL) 12 weeks after study drug cessation.

Original Primary Outcome Measures (submitted: December 21, 2011)

Efficacy 12 weeks post dosing [ Time Frame: SVR 12 ]

Efficacy of PSI-7977 in combination with RBV administered for 12 weeks compared with PEG/RBV administered for 24 weeks in treatment-naïve patients with HCV genotype 2 or 3 as assessed by the rate of SVR12

• Change History: Complete list of historical versions of study NCT01497366 on ClinicalTrials.gov Archive Site

Current Secondary Outcome Measures (submitted: March 4, 2014)

• Number of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities [ Time Frame: Up to 24 weeks plus 30 days following the last dose of study drug ]
• Percentage of Participants With Sustained Virologic Response 24 Weeks After Stopping All Study Drugs (SVR24) [ Time Frame: Post-treatment Week 24 ]
  SVR24 was defined as HCV RNA < LLOQ 24 weeks after study drug cessation.
• Percentage of Participants With HCV RNA < LLOQ on Treatment [ Time Frame: Up to 12 Weeks ]
• Change From Baseline in HCV RNA [ Time Frame: Baseline to Week 12 ]
• Percentage of Participants With Virologic Failure During Treatment [ Time Frame: Baseline up to Week 24 ]
  Virologic failure was defined as either

  • Viral breakthrough: HCV RNA ≥ 25 IU/mL after having previously had HCV RNA < 25 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement
  • Viral rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement
  • Non-response: HCV RNA persistently ≥ 25 IU/ml while on treatment (through Week 12)
• Percentage of Participants With Viral Relapse Following Treatment [ Time Frame: Up to Post-treatment Week 24 ]
  Viral relapse was defined as HCV RNA ≥ 25 IU/mL in post-treatment after having achieved < LLOQ at last on-treatment measurement, confirmed with 2 consecutive values or last available measurement.

Original Secondary Outcome Measures (submitted: December 21, 2011)

• Description of Safety with PSI-7977 and ribavirin [ Time Frame: 12 Weeks ]
  Safety and tolerability of PSI-7977/RBV administered for 12 weeks as measured by the frequency of deaths, serious adverse events (SAEs), discontinuations due to AEs, and Grade 3 or 4 laboratory abnormalities
• SVR 24 [ Time Frame: 24 Weeks after treatment ]
  To determine the SVR at Week 24 (SVR24) following completion of treatment for each investigational arm
• Amount of circulating HCV RNA [ Time Frame: 12 or 24 weeks post dosing ]
  To evaluate the change in circulating HCV RNA in patients over 12 or 24 weeks of dosing
• ALT normalization [ Time Frame: 24 weeks ]
  To determine the proportion of patients whose ALT normalizes during therapy
• Number of subjects with virologic failure [ Time Frame: 24 Weeks ]
  To describe rates of virologic failure
• Characterization of drug resistance [ Time Frame: 24 Weeks ]
  To characterize HCV drug resistance substitutions at baseline, during, and after therapy with PSI-7977

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

Descriptive Information

• Brief Title: Phase 3 Study of Sofosbuvir and Ribavirin
• Official Title: A Phase 3, Multicenter, Randomized, Active-Controlled Study to Investigate the Safety and Efficacy of PSI-7977 and Ribavirin for 12 Weeks Compared to Pegylated Interferon and Ribavirin for 24 Weeks in Treatment-Naïve Patients With Chronic Genotype 2 or 3 HCV Infection
• Brief Summary: This study was to assess the safety and efficacy of sofosbuvir (GS-7977; PSI-7977) in combination with ribavirin (RBV) administered for 12 weeks compared with pegylated interferon (PEG)/RBV administered for 24 weeks in treatment-naive patients with Hepatitis C (HCV) genotype 2 or 3. Efficacy was assessed by the rate of sustained viral response (SVR) 12 weeks after the discontinuation of therapy (SVR12). This was a non-inferiority study, and if non-inferiority was demonstrated, the study was then allowed to test for superiority.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C

Intervention

• Drug: Sofosbuvir
  Sofosbuvir 400 mg (2 × 200 mg tablets) administered orally once daily
  Other Names:

  • Sovaldi™
  • GS-7977
  • PSI-7977
• Drug: PEG
  Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
  Other Name: Pegasys®
• Drug: RBV

  Ribavirin (RBV) administered as 200 mg tablets up to 1200 mg in a divided daily dose

  • Dose of sofosbuvir+RBV group based on baseline weight: < 75kg = 1000 mg and ≥ 75 kg = 1200 mg
  • Dose of PEG+RBV group: 800 mg

Study Arms

• Experimental: Sofosbuvir+RBV
  Participants were randomized to receive sofosbuvir+RBV for 12 weeks.
  Interventions:

  • Drug: Sofosbuvir
  • Drug: RBV
• Active Comparator: PEG+RBV
  Participants were randomized to receive PEG+RBV for 24 weeks.
  Interventions:

  • Drug: PEG
  • Drug: RBV

Publications *

• 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.
• Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh AM, Younossi Z, Gane EJ. Sofosbuvir for previously untreated chronic hepatitis C infection. N Engl J Med. 2013 May 16;368(20):1878-87. doi: 10.1056/NEJMoa1214853. Epub 2013 Apr 23.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 4, 2014): 527
• Original Estimated Enrollment (submitted: December 21, 2011): 500
• Actual Study Completion Date: April 2013
• Actual Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Chronic Genotype 2 or 3 HCV-infection
• Naive to all HCV antiviral treatment(s)

Exclusion Criteria:

• Positive test at Screening for HBsAg, anti-hepatitis B core immunoglobulin M antibody (anti-HBc IgM Ab), or anti-HIV Ab
• History of any other clinically significant chronic liver disease
• A history consistent with decompensated liver disease
• History or current evidence of psychiatric illness, immunologic disorder, hemoglobinopathy, pulmonary or cardiac disease, seizure disorder or anticonvulsant use, poorly controlled diabetes, cancer, or a history of malignancy, that makes the subject unsuitable for the study.
• Participation in a clinical study within 3 months prior to first dose

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: Australia, Canada, Italy, Netherlands, New Zealand, Puerto Rico, Sweden, United States

Administrative Information

• NCT Number: NCT01497366
• Other Study ID Numbers: P7977-1231
• 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: March 2014