Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir in Adults With Chronic HCV Infection Who Have Previously Received Treatment With Direct-Acting Antiviral Therapy (POLARIS-1)

• ClinicalTrials.gov Identifier: NCT02607735
• Recruitment Status: Completed
• First Posted: November 18, 2015
• Results First Posted: December 13, 2017
• Last Update Posted: March 5, 2019
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: November 16, 2015
• First Posted Date: November 18, 2015
• Results First Submitted Date: October 4, 2017
• Results First Posted Date: December 13, 2017
• Last Update Posted Date: March 5, 2019
• Actual Study Start Date: November 11, 2015
• Actual Primary Completion Date: October 10, 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 14, 2017)

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

Original Primary Outcome Measures (submitted: November 16, 2015)

• Proportion of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study) [ Time Frame: Posttreatment Week 12 ]
  SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
• Proportion of Participants Who Permanently Discontinue Study Drug Due to an Adverse Event [ Time Frame: Up to 12 weeks ]

Current Secondary Outcome Measures (submitted: July 23, 2018)

• Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) [ Time Frame: Posttreatment Week 4 ]
  SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment, respectively.
• Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) [ Time Frame: Weeks 1, 2, 4, 8 and 12 ]
• Change From Baseline in HCV RNA (Primary Study) [ Time Frame: Baseline; Weeks 1, 2, 4, 8 and 12 ]
• Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study) [ Time Frame: Posttreatment Week 24 ]
  SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
• Percentage of Participants With Virologic Failure (Primary Study) [ Time Frame: Up to Posttreatment Week 24 ]
  Virologic failure is 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.
• Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) [ Time Frame: Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy) ]
  SVR4, SVR12 and SVR24 was defined as HCV RNA < LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively.
• Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) [ Time Frame: Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy) ]
• Change From Baseline in HCV RNA (Deferred Treatment Substudy) [ Time Frame: Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy) ]
• Percentage of Participants With Virologic Failure (Deferred Treatment Substudy) [ Time Frame: Up to Posttreatment Week 24 (Deferred Treatment Substudy) ]
  Virologic failure is 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.

Original Secondary Outcome Measures (submitted: November 16, 2015)

• Proportion of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) (Primary Study) [ Time Frame: Posttreatment Weeks 4 and 24 ]
  SVR4 and SVR 24 are defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
• Proportion of Participants With HCV RNA < LLOQ On Treatment (Primary Study) [ Time Frame: Up to 12 weeks ]
• Change From Baseline in HCV RNA (Primary Study) [ Time Frame: Up to 12 weeks ]
• Proportion of Participants With Virologic Failure (Primary Study) [ Time Frame: Up to Posttreatment Week 24 ]
  Virologic failure is defined as:

  • On-treatment virologic failure:
    • Confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment, or
    • Confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, or
    • HCV RNA persistently ≥ LLOQ through 8 weeks of treatment
  • Viral relapse
• Proportion of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) [ Time Frame: Posttreatment Weeks 4, 12, and 24 on active treatment ]
  This outcome will be assessed in participants randomized to placebo who later enroll in deferred treatment.
• Proportion of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) [ Time Frame: Up to 12 weeks on active treatment ]
  This outcome will be assessed in participants randomized to placebo who later enroll in deferred treatment.
• Change From Baseline in HCV RNA (Deferred Treatment Substudy) [ Time Frame: Up to 12 weeks on active treatment ]
  This outcome will be assessed in participants randomized to placebo who later enroll in deferred treatment.
• Proportion of Participants With Virologic Failure (Deferred Treatment Substudy) [ Time Frame: Up to Posttreatment Week 24 on active treatment ]
  This outcome will be assessed in participants randomized to placebo who later enroll in deferred treatment.

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

Descriptive Information

• Brief Title: Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir in Adults With Chronic HCV Infection Who Have Previously Received Treatment With Direct-Acting Antiviral Therapy
• Official Title: A Phase 3, Global, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Investigate the Safety and Efficacy of Sofosbuvir/Velpatasvir/GS-9857 Fixed-Dose Combination for 12 Weeks in Direct-Acting Antiviral-Experienced Subjects With Chronic HCV Infection

Brief Summary

The primary objectives of this study are to evaluate the safety and efficacy of treatment with sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) in adults with chronic hepatitis C virus (HCV) infection who have previously received treatment with direct-acting antiviral therapy.

Participants randomized to placebo may be eligible for deferred treatment with active SOF/VEL/VOX.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Treatment
• Condition: Hepatitis C

Intervention

• Drug: SOF/VEL/VOX
  400/100/100 mg fixed dose-combination (FDC) tablet administered orally once daily with food
  Other Names:

  • Vosevi®
  • GS-7977/GS-5816/GS-9857
• Drug: Placebo
  Tablet administered orally once daily with food

Study Arms

• Experimental: SOF/VEL/VOX (Primary Study)
  SOF/VEL/VOX for 12 weeks
  Intervention: Drug: SOF/VEL/VOX
• Experimental: Placebo (Primary Study)
  Placebo to match SOF/VEL/VOX for 12 weeks
  Intervention: Drug: Placebo
• Experimental: SOF/VEL/VOX (Deferred Treatment Substudy)
  SOF/VEL/VOX for 12 weeks for eligible participants initially randomized to receive placebo
  Intervention: Drug: SOF/VEL/VOX

Publications *

• Bourlière M, Gordon SC, Ramji A, Ravendhran N, Tran TT, Hyland RH, et al. Sofosbuvir/Velpatasvir/Voxilaprevir for 12 Weeks as a Salvage Regimen in NS5A Inhibitor-Experienced Patients with Genotype 1-6 Infection: The Phase 3 POLARIS-1 Study [Abstract 194]. J Hepatology 2016;63 (1S):102A.
• Younossi ZM, Stepanova M, Gordon S, Zeuzem S, Mann MP, Jacobson I, Bourliere M, Cooper C, Flamm S, Reddy KR, Kowdley K, Younossi I, Hunt S. Patient-Reported Outcomes Following Treatment of Chronic Hepatitis C Virus Infection With Sofosbuvir and Velpatasvir, With or Without Voxilaprevir. Clin Gastroenterol Hepatol. 2018 Apr;16(4):567-574.e6. doi: 10.1016/j.cgh.2017.11.023. Epub 2017 Nov 16.
• Bourlière M, Gordon SC, Schiff ER, Tran TT, Ravendhran N, Landis CS, Hyland RH, Stamm LM, Zhang J, Dvory-Sobol H, Subramanian GM, Brainard DM, McHutchison JG, Serfaty L, Thompson AJ, Sepe TE, Curry MP, Reddy KR, Manns MP. Deferred treatment with sofosbuvir-velpatasvir-voxilaprevir for patients with chronic hepatitis C virus who were previously treated with an NS5A inhibitor: an open-label substudy of POLARIS-1. Lancet Gastroenterol Hepatol. 2018 Aug;3(8):559-565. doi: 10.1016/S2468-1253(18)30118-3. Epub 2018 May 31.
• Bourlière M, Gordon SC, Flamm SL, Cooper CL, Ramji A, Tong M, Ravendhran N, Vierling JM, Tran TT, Pianko S, Bansal MB, de Lédinghen V, Hyland RH, Stamm LM, Dvory-Sobol H, Svarovskaia E, Zhang J, Huang KC, Subramanian GM, Brainard DM, McHutchison JG, Verna EC, Buggisch P, Landis CS, Younes ZH, Curry MP, Strasser SI, Schiff ER, Reddy KR, Manns MP, Kowdley KV, Zeuzem S; POLARIS-1 and POLARIS-4 Investigators. Sofosbuvir, Velpatasvir, and Voxilaprevir for Previously Treated HCV Infection. N Engl J Med. 2017 Jun 1;376(22):2134-2146. doi: 10.1056/NEJMoa1613512.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 22, 2016): 416
• Original Estimated Enrollment (submitted: November 16, 2015): 380
• Actual Study Completion Date: June 21, 2017
• Actual Primary Completion Date: October 10, 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Willing and able to provide written informed consent
• HCV RNA ≥ 10^4 IU/mL at screening
• Chronic HCV infection (≥ 6 months)
• Treatment experienced with a direct acting antiviral medication for HCV
• Use of protocol specified methods of contraception

Key Exclusion Criteria:

• Current or prior history of clinically significant illness that may interfere with participation in the study
• Screening ECG with clinically significant abnormalities
• Laboratory results outside of acceptable ranges at screening
• Pregnant or nursing female
• Chronic liver disease not caused by HCV
• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

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

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, France, Germany, New Zealand, Puerto Rico, United Kingdom, United States

Administrative Information

• NCT Number: NCT02607735
• Other Study ID Numbers: GS-US-367-1171; 2015-003455-21 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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 https://www.gilead.com/about/ethics-and-code-of-conduct/policies.
• Supporting Materials: Study Protocol
• Supporting Materials: Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: https://www.gilead.com/about/ethics-and-code-of-conduct/policies

• Responsible Party: Gilead Sciences
• Study Sponsor: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: July 2018