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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT02607735




Registration number
NCT02607735
Ethics application status
Date submitted
16/11/2015
Date registered
18/11/2015
Date last updated
5/03/2019

Titles & IDs
Public title
Safety and Efficacy of Sofosbuvir/Velpatasvir/Voxilaprevir in Adults With Chronic HCV Infection Who Have Previously Received Treatment With Direct-Acting Antiviral Therapy
Scientific 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
Secondary ID [1] 0 0
2015-003455-21
Secondary ID [2] 0 0
GS-US-367-1171
Universal Trial Number (UTN)
Trial acronym
POLARIS-1
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Hepatitis C 0 0
Condition category
Condition code
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SOF/VEL/VOX
Treatment: Drugs - Placebo

Experimental: SOF/VEL/VOX (Primary Study) - SOF/VEL/VOX for 12 weeks

Experimental: Placebo (Primary Study) - Placebo to match SOF/VEL/VOX for 12 weeks

Experimental: SOF/VEL/VOX (Deferred Treatment Substudy) - SOF/VEL/VOX for 12 weeks for eligible participants initially randomized to receive placebo


Treatment: Drugs: SOF/VEL/VOX
400/100/100 mg fixed dose-combination (FDC) tablet administered orally once daily with food

Treatment: Drugs: Placebo
Tablet administered orally once daily with food

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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.
Timepoint [1] 0 0
Posttreatment Week 12
Primary outcome [2] 0 0
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study)
Timepoint [2] 0 0
Up to 12 weeks
Secondary outcome [1] 0 0
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.
Timepoint [1] 0 0
Posttreatment Week 4
Secondary outcome [2] 0 0
Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study)
Timepoint [2] 0 0
Weeks 1, 2, 4, 8 and 12
Secondary outcome [3] 0 0
Change From Baseline in HCV RNA (Primary Study)
Timepoint [3] 0 0
Baseline; Weeks 1, 2, 4, 8 and 12
Secondary outcome [4] 0 0
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.
Timepoint [4] 0 0
Posttreatment Week 24
Secondary outcome [5] 0 0
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.
Timepoint [5] 0 0
Up to Posttreatment Week 24
Secondary outcome [6] 0 0
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.
Timepoint [6] 0 0
Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy)
Secondary outcome [7] 0 0
Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy)
Timepoint [7] 0 0
Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy)
Secondary outcome [8] 0 0
Change From Baseline in HCV RNA (Deferred Treatment Substudy)
Timepoint [8] 0 0
Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy)
Secondary outcome [9] 0 0
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.
Timepoint [9] 0 0
Up to Posttreatment Week 24 (Deferred Treatment Substudy)

Eligibility
Key inclusion criteria
Key

- 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
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC
Recruitment hospital [1] 0 0
- Camperdown
Recruitment hospital [2] 0 0
- Darlinghurst
Recruitment hospital [3] 0 0
- Herston
Recruitment hospital [4] 0 0
- Clayton
Recruitment hospital [5] 0 0
- Fitzroy
Recruitment hospital [6] 0 0
- Melbourne
Recruitment postcode(s) [1] 0 0
- Camperdown
Recruitment postcode(s) [2] 0 0
- Darlinghurst
Recruitment postcode(s) [3] 0 0
- Herston
Recruitment postcode(s) [4] 0 0
- Clayton
Recruitment postcode(s) [5] 0 0
- Fitzroy
Recruitment postcode(s) [6] 0 0
- Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Illinois
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New Jersey
Country [13] 0 0
United States of America
State/province [13] 0 0
New York
Country [14] 0 0
United States of America
State/province [14] 0 0
North Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
Rhode Island
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
United States of America
State/province [22] 0 0
Wisconsin
Country [23] 0 0
Canada
State/province [23] 0 0
Alberta
Country [24] 0 0
Canada
State/province [24] 0 0
British Columbia
Country [25] 0 0
Canada
State/province [25] 0 0
Ontario
Country [26] 0 0
Canada
State/province [26] 0 0
Quebec
Country [27] 0 0
France
State/province [27] 0 0
Clermont-Ferrand
Country [28] 0 0
France
State/province [28] 0 0
Clichy
Country [29] 0 0
France
State/province [29] 0 0
Creteil
Country [30] 0 0
France
State/province [30] 0 0
Grenoble
Country [31] 0 0
France
State/province [31] 0 0
Lille
Country [32] 0 0
France
State/province [32] 0 0
Limoges
Country [33] 0 0
France
State/province [33] 0 0
Lyon
Country [34] 0 0
France
State/province [34] 0 0
Marseille
Country [35] 0 0
France
State/province [35] 0 0
Montpellier
Country [36] 0 0
France
State/province [36] 0 0
Nice
Country [37] 0 0
France
State/province [37] 0 0
Paris
Country [38] 0 0
France
State/province [38] 0 0
Pessac
Country [39] 0 0
France
State/province [39] 0 0
Rennes
Country [40] 0 0
France
State/province [40] 0 0
Rouen
Country [41] 0 0
France
State/province [41] 0 0
Strasbourg
Country [42] 0 0
France
State/province [42] 0 0
Toulouse
Country [43] 0 0
France
State/province [43] 0 0
Vandoeuvre-les-Nancy
Country [44] 0 0
France
State/province [44] 0 0
Villejuif
Country [45] 0 0
Germany
State/province [45] 0 0
Berlin
Country [46] 0 0
Germany
State/province [46] 0 0
Bonn
Country [47] 0 0
Germany
State/province [47] 0 0
Frankfurt am Main
Country [48] 0 0
Germany
State/province [48] 0 0
Hamburg
Country [49] 0 0
Germany
State/province [49] 0 0
Hannover
Country [50] 0 0
Germany
State/province [50] 0 0
Köln
Country [51] 0 0
New Zealand
State/province [51] 0 0
Christchurch
Country [52] 0 0
New Zealand
State/province [52] 0 0
Grafton
Country [53] 0 0
Puerto Rico
State/province [53] 0 0
San Juan
Country [54] 0 0
United Kingdom
State/province [54] 0 0
London
Country [55] 0 0
United Kingdom
State/province [55] 0 0
Manchester
Country [56] 0 0
United Kingdom
State/province [56] 0 0
Nottingham
Country [57] 0 0
United Kingdom
State/province [57] 0 0
Portsmouth

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT02607735
Trial related presentations / 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.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications