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

Hepatitis C Clinical Trial

— POLARIS-1  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02607735
• Other study ID #: GS-US-367-1171
• Secondary ID: 2015-003455-21
• Status: Completed
• Phase: Phase 3
• Start date: November 11, 2015
• Est. completion date: June 21, 2017

Study information

• Verified date: July 2018
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 416
• Est. completion date: June 21, 2017
• Est. primary completion date: October 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis C
• Infection

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

References & Publications (4)

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 — View Citation

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.

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Primary	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study)		Up to 12 weeks
Secondary	Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study)	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment, respectively.	Posttreatment Week 4
Secondary	Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study)		Weeks 1, 2, 4, 8 and 12
Secondary	Change From Baseline in HCV RNA (Primary Study)		Baseline; Weeks 1, 2, 4, 8 and 12
Secondary	Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study)	SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.	Posttreatment Week 24
Secondary	Percentage of Participants With Virologic Failure (Primary Study)	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.	Up to Posttreatment Week 24
Secondary	Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy)	SVR4, SVR12 and SVR24 was defined as HCV RNA < LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively.	Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy)
Secondary	Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy)		Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy)
Secondary	Change From Baseline in HCV RNA (Deferred Treatment Substudy)		Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy)
Secondary	Percentage of Participants With Virologic Failure (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.	Up to Posttreatment Week 24 (Deferred Treatment Substudy)