Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 or 24 Weeks in Participants With Chronic Genotype 1 or 2 Hepatitis C Virus Infection Who Have Previously Failed a Direct-Acting Antiviral-Containing Regimen

• ClinicalTrials.gov Identifier: NCT02822794
• Recruitment Status: Completed
• First Posted: July 4, 2016
• Results First Posted: July 3, 2018
• Last Update Posted: November 14, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

Brief Summary:

The primary objective of this study is to evaluate the antiviral efficacy, safety, and tolerability of therapy with sofosbuvir/velpatasvir (SOF/VEL) fixed-dose combination (FDC) and ribavirin (RBV) in participants with chronic genotype 1 or 2 hepatitis C virus (HCV) infection who have previously failed a direct-acting antiviral (DAA)-containing regimen.

Condition or disease	Intervention/treatment	Phase
Hepatitis C Virus Infection	Drug: SOF/VEL; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 117 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3, Multicenter, Randomized, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Velpatasvir Fixed-Dose Combination and Ribavirin for 12 or 24 Weeks in Subjects With Chronic Genotype 1 or 2 HCV Infection Who Have Previously Failed a Direct-Acting Antiviral-Containing Regimen
• Actual Study Start Date: July 25, 2016
• Actual Primary Completion Date: June 2, 2017
• Actual Study Completion Date: August 25, 2017

Arms and Interventions

Arm	Intervention/treatment
Experimental: SOF/VEL FDC + RBV 12 weeks; SOF/VEL FDC + RBV for 12 weeks in participants with genotype 1 or 2 HCV infection	Drug: SOF/VEL; 400/100 mg tablet administered orally once daily; Other Names: GS-7977/GS-5816; Epclusa®; Drug: RBV; Capsules administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg); Other Name: REBETOL®
Experimental: SOF/VEL FDC + RBV 24 weeks; SOF/VEL FDC + RBV for 24 weeks in participants with genotype 1 or 2 HCV infection	Drug: SOF/VEL; 400/100 mg tablet administered orally once daily; Other Names: GS-7977/GS-5816; Epclusa®; Drug: RBV; Capsules administered orally in a divided daily dose according to package insert weight-based dosing recommendations (≤ 60 kg = 600 mg, > 60 kg to ≤ 80 kg = 800 mg, and ≥ 80 kg = 1000 mg); Other Name: REBETOL®

Outcome Measures

Primary Outcome Measures :

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.
2. Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 24 weeks ]

Secondary Outcome Measures :

1. Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
   SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
2. Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
   SVR 24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
3. Percentage of Participants With HCV RNA < LLOQ at Week 1 [ Time Frame: Week 1 ]
4. Percentage of Participants With HCV RNA < LLOQ at Week 2 [ Time Frame: Week 2 ]
5. Percentage of Participants With HCV RNA < LLOQ at Week 3 [ Time Frame: Week 3 ]
6. Percentage of Participants With HCV RNA < LLOQ at Week 4 [ Time Frame: Week 4 ]
7. Percentage of Participants With HCV RNA < LLOQ at Week 5 [ Time Frame: Week 5 ]
8. Percentage of Participants With HCV RNA < LLOQ at Week 6 [ Time Frame: Week 6 ]
9. Percentage of Participants With HCV RNA < LLOQ at Week 8 [ Time Frame: Week 8 ]
10. Percentage of Participants With HCV RNA < LLOQ at Week 10 [ Time Frame: Week 10 ]
11. Percentage of Participants With HCV RNA < LLOQ at Week 12 [ Time Frame: Week 12 ]
12. Percentage of Participants With HCV RNA < LLOQ at Week 16 [ Time Frame: Week 16 ]
13. Percentage of Participants With HCV RNA < LLOQ at Week 20 [ Time Frame: Week 20 ]
14. Percentage of Participants With HCV RNA < LLOQ at Week 24 [ Time Frame: Week 24 ]
15. Change From Baseline in HCV RNA at Week 1 [ Time Frame: Baseline; Week 1 ]
16. Change From Baseline in HCV RNA at Week 2 [ Time Frame: Baseline; Week 2 ]
17. Change From Baseline in HCV RNA at Week 3 [ Time Frame: Baseline; Week 3 ]
18. Change From Baseline in HCV RNA at Week 4 [ Time Frame: Baseline; Week 4 ]
19. Change From Baseline in HCV RNA at Week 5 [ Time Frame: Baseline; Week 5 ]
20. Change From Baseline in HCV RNA at Week 6 [ Time Frame: Baseline; Week 6 ]
21. Change From Baseline in HCV RNA at Week 8 [ Time Frame: Baseline; Week 8 ]
22. Change From Baseline in HCV RNA at Week 10 [ Time Frame: Baseline; Week 10 ]
23. Change From Baseline in HCV RNA at Week 12 [ Time Frame: Baseline; Week 12 ]
24. Change From Baseline in HCV RNA at Week 16 [ Time Frame: Baseline; Week 16 ]
25. Change From Baseline in HCV RNA at Week 20 [ Time Frame: Baseline; Week 20 ]
26. Change From Baseline in HCV RNA at Week 24 [ Time Frame: Baseline; Week 24 ]
27. Percentage of Participants With Overall Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]

    Virologic failure was defined as:

    • On-treatment virologic failure:

      • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
      • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
      • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)

    • Virologic relapse:

      • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.

Eligibility Criteria

• Ages Eligible for Study: 20 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Key Inclusion Criteria:

• Genotype 1 or 2 HCV infection
• Chronic HCV infection (≥ 6 months prior to screening) documented by prior medical history or liver biopsy
• Previously treated with a DAA-containing regimen of at least 4 week duration

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Contacts and Locations

Locations

Japan

Ehime, Japan

Hiroshima, Japan

Ichikawa-shi, Japan

Iruma-gun, Japan

Kashihara, Japan

Kurume-shi, Japan

Kyoto, Japan

Maebashi, Japan

Musashino-shi, Japan

Nagoya, Japan

Nishinomiya, Japan

Ogaki City, Japan

Okayama, Japan

Omura, Japan

Sapporo, Japan

Suita, Japan

Takamatsu-shi, Japan

Yamagata, Japan

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

  Study Documents (Full-Text)

Documents provided by Gilead Sciences:

Statistical Analysis Plan  [PDF] June 13, 2017

Study Protocol  [PDF] June 13, 2016

More Information

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02822794 History of Changes
• Other Study ID Numbers: GS-US-342-3921
• First Posted: July 4, 2016
• Results First Posted: July 3, 2018
• Last Update Posted: November 14, 2018
• Last Verified: July 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes

Additional relevant MeSH terms:

Hepatitis C; Infection; Communicable Diseases; Hepatitis A; Hepatitis; Virus Diseases; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Ribavirin; Antiviral Agents; Sofosbuvir; Velpatasvir; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents