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

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02607735
• Collaborator: (none)
• Enrollment: 416
• Locations: 86
• Arms: 3
• Actual Duration (Months): 19.3
• Patients Per Site: 4.8
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis C	Drug: SOF/VEL/VOX; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 416 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: Nov 11, 2015
• Actual Primary Completion Date: Oct 10, 2016
• Actual Study Completion Date: Jun 21, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: SOF/VEL/VOX (Primary Study) SOF/VEL/VOX for 12 weeks	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
Experimental: Placebo (Primary Study) Placebo to match SOF/VEL/VOX for 12 weeks	Drug: Placebo; Tablet administered orally once daily with food
Experimental: SOF/VEL/VOX (Deferred Treatment Substudy) SOF/VEL/VOX for 12 weeks for eligible participants initially randomized to receive placebo	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

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.

2. Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study) [Up to 12 weeks]

Secondary Outcome Measures

1. Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study) [Posttreatment Week 4]

   SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment, respectively.

2. Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study) [Weeks 1, 2, 4, 8 and 12]

3. Change From Baseline in HCV RNA (Primary Study) [Baseline; Weeks 1, 2, 4, 8 and 12]

4. Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study) [Posttreatment Week 24]

   SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

5. Percentage of Participants With Virologic Failure (Primary Study) [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.

6. Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy) [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.

7. Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy) [Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy)]

8. Change From Baseline in HCV RNA (Deferred Treatment Substudy) [Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy)]

9. Percentage of Participants With Virologic Failure (Deferred Treatment Substudy) [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Long Beach	California	United States
2		Los Angeles	California	United States
3		Palo Alto	California	United States
4		Pasadena	California	United States
5		Rialto	California	United States
6		San Diego	California	United States
7		San Francisco	California	United States
8		Aurora	Colorado	United States
9		Englewood	Colorado	United States
10		Washington	District of Columbia	United States
11		Gainesville	Florida	United States
12		Miami	Florida	United States
13		Orlando	Florida	United States
14		Wellington	Florida	United States
15		Atlanta	Georgia	United States
16		Marietta	Georgia	United States
17		Chicago	Illinois	United States
18		Indianapolis	Indiana	United States
19		Baltimore	Maryland	United States
20		Catonsville	Maryland	United States
21		Boston	Massachusetts	United States
22		Ann Arbor	Michigan	United States
23		Detroit	Michigan	United States
24		Kansas City	Missouri	United States
25		Saint Louis	Missouri	United States
26		Hillsborough	New Jersey	United States
27		Bronx	New York	United States
28		New York	New York	United States
29		Asheville	North Carolina	United States
30		Philadelphia	Pennsylvania	United States
31		Pittsburgh	Pennsylvania	United States
32		Providence	Rhode Island	United States
33		Germantown	Tennessee	United States
34		Knoxville	Tennessee	United States
35		Nashville	Tennessee	United States
36		Houston	Texas	United States
37		San Antonio	Texas	United States
38		Murray	Utah	United States
39		Falls Church	Virginia	United States
40		Norfolk	Virginia	United States
41		Richmond	Virginia	United States
42		Seattle	Washington	United States
43		Madison	Wisconsin	United States
44		Camperdown	New South Wales	Australia
45		Darlinghurst	New South Wales	Australia
46		Herston	Queensland	Australia
47		Clayton	Victoria	Australia
48		Fitzroy	Victoria	Australia
49		Melbourne	Victoria	Australia
50		Calgary	Alberta	Canada
51		Edmonton	Alberta	Canada
52		Vancouver	British Columbia	Canada
53		Brampton	Ontario	Canada
54		Toronto	Ontario	Canada
55		Montreal	Quebec	Canada
56		Clermont-Ferrand		France
57		Clichy		France
58		Creteil		France
59		Grenoble		France
60		Lille		France
61		Limoges		France
62		Lyon		France
63		Marseille		France
64		Montpellier		France
65		Nice		France
66		Paris		France
67		Pessac		France
68		Rennes		France
69		Rouen		France
70		Strasbourg		France
71		Toulouse		France
72		Vandoeuvre-les-Nancy		France
73		Villejuif		France
74		Berlin		Germany
75		Bonn		Germany
76		Frankfurt am Main		Germany
77		Hamburg		Germany
78		Hannover		Germany
79		Köln		Germany
80		Christchurch		New Zealand
81		Grafton		New Zealand
82		San Juan		Puerto Rico
83		London		United Kingdom
84		Manchester		United Kingdom
85		Nottingham		United Kingdom
86		Portsmouth		United Kingdom

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

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.
• 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.
• 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.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02607735
• Other Study ID Numbers: GS-US-367-1171; 2015-003455-21
• First Posted: Nov 18, 2015
• Last Update Posted: Mar 5, 2019
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Gilead Sciences: Chronic Hepatitis C Infection
• Additional relevant MeSH terms: Infections; Hepatitis C; Hepatitis; Sofosbuvir; Velpatasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in North America, Europe, and Asia Pacific. The first participant was screened on 11 November 2015. The last study visit occurred on 21 June 2017.
Pre-assignment Detail	520 participants were screened.

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)	SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) (400/100/100 mg) fixed-dose combination (FDC) tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks	Participants who completed placebo treatment were eligible to enroll in to the open-label Deferred Treatment Substudy to receive SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks.
Period Title: Primary Study
STARTED	264	152	0
COMPLETED	257	152	0
NOT COMPLETED	7	0	0
Period Title: Primary Study
STARTED	0	0	147
COMPLETED	0	0	142
NOT COMPLETED	0	0	5

Baseline Characteristics

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)	Total
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks	Total of all reporting groups
Overall Participants	263	152	415
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	58 (8.5)	59 (8.0)	58 (8.5)
Sex: Female, Male (Count of Participants)
Female	63 24%	31 20.4%	94 22.7%
Male	200 76%	121 79.6%	321 77.3%
Race/Ethnicity, Customized (Count of Participants)
White	211 80.2%	124 81.6%	335 80.7%
Black or African American	38 14.4%	22 14.5%	60 14.5%
Asian	8 3%	6 3.9%	14 3.4%
Native Hawaiian or Pacific Islander	3 1.1%	0 0%	3 0.7%
Not Disclosed	1 0.4%	0 0%	1 0.2%
American Indian or Alaska Native	1 0.4%	0 0%	1 0.2%
Other	1 0.4%	0 0%	1 0.2%
Race/Ethnicity, Customized (Count of Participants)
Hispanic or Latino	15 5.7%	10 6.6%	25 6%
Not Hispanic or Latino	247 93.9%	142 93.4%	389 93.7%
Not Disclosed	1 0.4%	0 0%	1 0.2%
Region of Enrollment (Count of Participants)
United States	135 51.3%	101 66.4%	236 56.9%
Australia	15 5.7%	11 7.2%	26 6.3%
Canada	28 10.6%	14 9.2%	42 10.1%
France	56 21.3%	16 10.5%	72 17.3%
Germany	16 6.1%	7 4.6%	23 5.5%
New Zealand	5 1.9%	2 1.3%	7 1.7%
United Kingdom	8 3%	1 0.7%	9 2.2%
IL28b Status (Count of Participants)
CC	47 17.9%	27 17.8%	74 17.8%
CT	165 62.7%	93 61.2%	258 62.2%
TT	51 19.4%	32 21.1%	83 20%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.3 (0.68)	6.3 (0.63)	6.3 (0.66)
HCV RNA Category (Count of Participants)
< 800,000 IU/mL	73 27.8%	36 23.7%	109 26.3%
≥ 800,000 IU/mL	190 72.2%	116 76.3%	306 73.7%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) (Primary Study)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ) at 12 weeks after stopping study treatment.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set (all randomized/enrolled participants who took at least 1 dose of study drug) in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 12 visit.

Arm/Group Title	SOF/VEL/VOX (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	263
Number (95% Confidence Interval) [percentage of participants]	96.2 36.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	SOF/VEL/VOX (Primary Study)
	Comments
	Type of Statistical Test	Superiority
	Comments	The SVR12 rate for the SOF/VEL/VOX group was compared to the performance goal of 85% using a 2-sided exact 1-sample binomial test at the 0.05 significance level.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	2-sided exact 1-sample binomial test
	Comments

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event (Primary Study)
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks
Measure Participants	263	152
Number [percentage of participants]	0.4 0.2%	2.0 1.3%

3. Secondary Outcome

Title	Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) (Primary Study)
Description	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment, respectively.
Time Frame	Posttreatment Week 4

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks
Measure Participants	263	152
Number (95% Confidence Interval) [percentage of participants]	97.7 37.1%	0 0%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ On Treatment (Primary Study)
Time Frame	Weeks 1, 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks
Measure Participants	263	152
Week 1	15.6 5.9%	0 0%
Week 2	56.7 21.6%	0 0%
Week 4	92.7 35.2%	0 0%
Week 8	100.0 38%	0 0%
Week 12	99.6 37.9%	0 0%

5. Secondary Outcome

Title	Change From Baseline in HCV RNA (Primary Study)
Time Frame	Baseline; Weeks 1, 2, 4, 8 and 12

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed.

Arm/Group Title	SOF/VEL/VOX (Primary Study)	Placebo (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks	Placebo tablet orally once daily with food for 12 weeks
Measure Participants	262	150
Week 1	-4.20 (0.733)	0.02 (0.300)
Week 2	-4.81 (0.704)	0.02 (0.322)
Week 4	-5.07 (0.677)	-0.01 (0.441)
Week 8	-5.11 (0.678)	0.05 (0.434)
Week 12	-5.10 (0.690)	0.03 (0.430)

6. Secondary Outcome

Title	Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) (Primary Study)
Description	SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.
Time Frame	Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 24 visit.

Arm/Group Title	SOF/VEL/VOX (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	263
Number (95% Confidence Interval) [percentage of participants]	96.2 36.6%

7. Secondary Outcome

Title	Percentage of Participants With Virologic Failure (Primary Study)
Description	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.
Time Frame	Up to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set in the SOF/VEL/VOX group were analyzed. This outcome measure was not assessed for participants in the Placebo group because they did not have a Posttreatment Week 24 visit.

Arm/Group Title	SOF/VEL/VOX (Primary Study)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	263
Number [percentage of participants]	2.7 1%

8. Secondary Outcome

Title	Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (Deferred Treatment Substudy)
Description	SVR4, SVR12 and SVR24 was defined as HCV RNA < LLOQ at 4, 12 and 24 weeks after stopping study treatment, respectively.
Time Frame	Posttreatment Weeks 4, 12, and 24 (Deferred Treatment Substudy)

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	147
SVR4	98.6 37.5%
SVR12	97.3 37%
SVR24	97.3 37%

9. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ On Treatment (Deferred Treatment Substudy)
Time Frame	Weeks 1, 2, 4, 8 and 12 (Deferred Treatment Substudy)

Outcome Measure Data

Analysis Population Description

Full Analysis Set from the Deferred Treatment Sub study: all enrolled participants who took at least 1 dose of study drug

Arm/Group Title	SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	147
Week 1	14.3 5.4%
Week 2	62.6 23.8%
Week 4	93.2 35.4%
Week 8	100.0 38%
Week 12	100.0 38%

10. Secondary Outcome

Title	Change From Baseline in HCV RNA (Deferred Treatment Substudy)
Time Frame	Baseline; Weeks 1, 2, 4, 8, and 12 (Deferred Treatment Substudy)

Outcome Measure Data

Analysis Population Description

Participants with available data in the Full Analysis Set of the Deferred Treatment Substudy were analyzed.

Arm/Group Title	SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	147
Week 1	-4.30 (0.626)
Week 2	-4.93 (0.602)
Week 4	-5.16 (0.512)
Week 8	-5.20 (0.532)
Week 12	-5.20 (0.532)

11. Secondary Outcome

Title	Percentage of Participants With Virologic Failure (Deferred Treatment Substudy)
Description	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.
Time Frame	Up to Posttreatment Week 24 (Deferred Treatment Substudy)

Outcome Measure Data

Analysis Population Description

Full Analysis Set in the Deferred Treatment Substudy

Arm/Group Title	SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
Measure Participants	147
Number [percentage of participants]	2.7 1%

Adverse Events

Time Frame	Primary Study: Up to 12 Weeks + 30 days; Deferred Treatment Substudy: Up to 12 Weeks + 30 days
Adverse Event Reporting Description	Safety Analysis Set: all participants who received at least 1 dose of study drug
Arm/Group Title	SOF/VEL/VOX (Primary Study)		Placebo (Primary Study)		SOF/VEL/VOX (Deferred Treatment Substudy)
Arm/Group Description	SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks		Placebo tablet orally once daily with food for 12 weeks		Participants who completed placebo treatment were eligible for open-label Deferred Treatment Substudy. SOF/VEL/VOX (400/100/100 mg) FDC tablet orally once daily with food for 12 weeks
All Cause Mortality
	SOF/VEL/VOX (Primary Study)		Placebo (Primary Study)		SOF/VEL/VOX (Deferred Treatment Substudy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/263 (0%)		0/152 (0%)		0/147 (0%)
Serious Adverse Events
	SOF/VEL/VOX (Primary Study)		Placebo (Primary Study)		SOF/VEL/VOX (Deferred Treatment Substudy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	5/263 (1.9%)		7/152 (4.6%)		6/147 (4.1%)
Cardiac disorders
Acute myocardial infarction	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Atrial fibrillation	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Ventricular fibrillation	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Gastrointestinal disorders
Mesenteric vein thrombosis	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Hepatobiliary disorders
Hepatic failure	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Infections and infestations
Pneumonia	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Scrotal infection	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Urosepsis	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Injury, poisoning and procedural complications
Subdural haematoma	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Wrist fracture	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adrenal neoplasm	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Basal cell carcinoma	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Hepatocellular carcinoma	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Ovarian cancer	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Nervous system disorders
Cerebral haemorrhage	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Generalised tonic-clonic seizure	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Seizure	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Psychiatric disorders
Schizophrenia	0/263 (0%)		1/152 (0.7%)		0/147 (0%)
Renal and urinary disorders
Nephrolithiasis	0/263 (0%)		0/152 (0%)		1/147 (0.7%)
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Vascular disorders
Arteritis	1/263 (0.4%)		0/152 (0%)		0/147 (0%)
Other (Not Including Serious) Adverse Events
	SOF/VEL/VOX (Primary Study)		Placebo (Primary Study)		SOF/VEL/VOX (Deferred Treatment Substudy)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	147/263 (55.9%)		80/152 (52.6%)		87/147 (59.2%)
Gastrointestinal disorders
Diarrhoea	48/263 (18.3%)		19/152 (12.5%)		28/147 (19%)
Nausea	37/263 (14.1%)		12/152 (7.9%)		21/147 (14.3%)
General disorders
Asthenia	20/263 (7.6%)		9/152 (5.9%)		3/147 (2%)
Fatigue	56/263 (21.3%)		30/152 (19.7%)		31/147 (21.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	8/263 (3%)		8/152 (5.3%)		9/147 (6.1%)
Back pain	11/263 (4.2%)		8/152 (5.3%)		7/147 (4.8%)
Nervous system disorders
Dizziness	11/263 (4.2%)		14/152 (9.2%)		7/147 (4.8%)
Headache	66/263 (25.1%)		26/152 (17.1%)		29/147 (19.7%)
Psychiatric disorders
Insomnia	19/263 (7.2%)		8/152 (5.3%)		5/147 (3.4%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

After conclusion of the study and without prior written approval from Gilead, investigators in this study may communicate, orally present, or publish in scientific journals or other media only after the following conditions have been met: The results of the study in their entirety have been publicly disclosed by or with the consent of Gilead in an abstract, manuscript, or presentation form; or The study has been completed at all study sites for at least 2 years