Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination (FDC) With and Without Ribavirin for the Treatment of HCV

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01701401
• Collaborator: (none)
• Enrollment: 870
• Locations: 88
• Arms: 4
• Duration (Months): 19
• Patients Per Site: 9.9
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir (LDV)/sofosbuvir (SOF) fixed-dose combination (FDC) tablets with or without ribavirin (RBV) administered for 12 and 24 weeks in treatment-naive subjects with chronic genotype 1 HCV infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Virus	Drug: LDV/SOF; Drug: RBV	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 870 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/GS-5885 Fixed-Dose Combination (FDC) +/- Ribavirin for 12 and 24 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection.
• Study Start Date: Sep 1, 2012
• Actual Primary Completion Date: Mar 1, 2014
• Actual Study Completion Date: Apr 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF 12 weeks LDV/SOF administered for 12 weeks	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977
Experimental: LDV/SOF+RBV 12 weeks LDV/SOF+RBV administered for 12 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977 ; Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: LDV/SOF 24 weeks LDV/SOF administered for 24 weeks	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977
Experimental: LDV/SOF+RBV 24 weeks LDV/SOF+RBV administered for 24 weeks.	Drug: LDV/SOF; LDV/SOF 90/400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977 ; Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Outcome Measures

Primary Outcome Measures

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

   SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.

2. Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug [Up to 24 weeks]

   The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.

Secondary Outcome Measures

1. Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug [Posttreatment Weeks 4 and 24]

   SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.

2. Percentage of Participants With HCV RNA < LLOQ at Week 2 [Week 2]

3. Percentage of Participants With HCV RNA < LLOQ at Week 4 [Week 4]

4. Percentage of Participants With HCV RNA < LLOQ at Week 8 [Week 8]

5. Change From Baseline in HCV RNA at Week 2 [Baseline; Week 2]

6. Change From Baseline in HCV RNA at Week 4 [Baseline; Week 4]

7. Change From Baseline in HCV RNA at Week 8 [Baseline; Week 8]

8. Percentage of Participants With Virologic Failure [Baseline to posttreatment Week 24]

   On-treatment virologic failure was defined as: Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment Virologic relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Age ≥ 18, with chronic genotype 1 HCV infection

• HCV treatment-naive

• HCV RNA > 10,000 IU/mL at screening

• Cirrhosis determination; a liver biopsy may be required

• Screening laboratory values within defined thresholds

• Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Pregnant or nursing female or male with pregnant female partner

• Co-infection with HIV or hepatitis B virus (HBV)

• Current or prior history of clinical hepatic decompensation

• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)

• Chronic use of systemic immunosuppressive agents

• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		La Jolla	California	United States
3		Long Beach	California	United States
4		Los Angeles	California	United States
5		Palo Alto	California	United States
6		Sacramento	California	United States
7		San Diego	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		Tampa	Florida	United States
15		Wellington	Florida	United States
16		Atlanta	Georgia	United States
17		Decatur	Georgia	United States
18		Marietta	Georgia	United States
19		Chicago	Illinois	United States
20		Indianapolis	Indiana	United States
21		Baltimore	Maryland	United States
22		Lutherville	Maryland	United States
23		Boston	Massachusetts	United States
24		Detroit	Michigan	United States
25		Rochester	Minnesota	United States
26		Saint Paul	Minnesota	United States
27		Kansas City	Missouri	United States
28		Saint Louis	Missouri	United States
29		Hillsborough	New Jersey	United States
30		Albuquerque	New Mexico	United States
31		Santa Fe	New Mexico	United States
32		Bronx	New York	United States
33		Manhasset	New York	United States
34		New York	New York	United States
35		Asheville	North Carolina	United States
36		Chapel Hill	North Carolina	United States
37		Durham	North Carolina	United States
38		Fayetteville	North Carolina	United States
39		Statesville	North Carolina	United States
40		Winston-Salem	North Carolina	United States
41		Cincinnati	Ohio	United States
42		Philadelphia	Pennsylvania	United States
43		Germantown	Tennessee	United States
44		Nashville	Tennessee	United States
45		Arlington	Texas	United States
46		Dallas	Texas	United States
47		Houston	Texas	United States
48		San Antonio	Texas	United States
49		Fairfax	Virginia	United States
50		Falls Church	Virginia	United States
51		Norfolk	Virginia	United States
52		Richmond	Virginia	United States
53		Seattle	Washington	United States
54		CHRU Lille		France
55		Clichy		France
56		Creteil		France
57		La Tronche		France
58		Lyon		France
59		Marseille		France
60		Nice		France
61		Paris		France
62		Berlin		Germany
63		Dusseldorf		Germany
64		Essen		Germany
65		Frankfurt		Germany
66		Freiburg		Germany
67		Hamburg		Germany
68		Hannover		Germany
69		Koln		Germany
70		Mainz		Germany
71		Bologna		Italy
72		Brescia		Italy
73		Milan		Italy
74		Padova		Italy
75		Palermo		Italy
76		Roma		Italy
77		San Giovanni Rotondo		Italy
78		Torino		Italy
79		San Juan		Puerto Rico
80		Barcelona		Spain
81		Madrid		Spain
82		Malaga		Spain
83		Santander		Spain
84		Sevilla		Spain
85		Birmingham	Wstmid	United Kingdom
86		London		United Kingdom
87		Manchester		United Kingdom
88		Plymouth		United Kingdom

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Jenny Yang, Pharm D, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01701401
• Other Study ID Numbers: GS-US-337-0102; 2012-003387-43
• First Posted: Oct 5, 2012
• Last Update Posted: Nov 16, 2018
• Last Verified: Mar 1, 2015

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Gilead Sciences: HCV genotype 1 (GT-1); HCV; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; GS-7977; GS-5885; Ribavirin; Open Label; Sofosbuvir; Additional relevant MeSH terms:; Hepatitis; Hepatitis, Chronic; Hepatitis C; Hepatitis C, Chronic; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Flaviviridae Infections; Antiviral Agents; Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Antimetabolites; Molecular Mechanisms of Pharmacological Action
• Additional relevant MeSH terms: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 100 study sites in the United States and Europe. The first participant was screened on 26 September 2012. The last study visit occurred on 30 April 2014.
Pre-assignment Detail	1015 participants were screened.

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus ribavirin (RBV) tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Period Title: Overall Study
STARTED	217	218	217	218
COMPLETED	207	209	212	212
NOT COMPLETED	10	9	5	6

Baseline Characteristics

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks	Total
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks	Total of all reporting groups
Overall Participants	214	217	217	217	865
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52 (10.7)	52 (11.5)	53 (10.3)	53 (9.9)	52 (10.6)
Sex: Female, Male (Count of Participants)
Female	87 40.7%	89 41%	78 35.9%	98 45.2%	352 40.7%
Male	127 59.3%	128 59%	139 64.1%	119 54.8%	513 59.3%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	24 11.2%	26 12%	32 14.7%	26 12%	108 12.5%
White	187 87.4%	188 86.6%	177 81.6%	183 84.3%	735 85%
Asian	1 0.5%	0 0%	5 2.3%	5 2.3%	11 1.3%
American Indian/Alaska Native	0 0%	1 0.5%	0 0%	1 0.5%	2 0.2%
Hawaiian or Pacific Islander	0 0%	0 0%	1 0.5%	0 0%	1 0.1%
Other	2 0.9%	1 0.5%	2 0.9%	1 0.5%	6 0.7%
Not Disclosed	0 0%	1 0.5%	0 0%	1 0.5%	2 0.2%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	26 12.1%	20 9.2%	29 13.4%	26 12%	101 11.7%
Not Hispanic or Latino	187 87.4%	197 90.8%	188 86.6%	190 87.6%	762 88.1%
Not Disclosed	1 0.5%	0 0%	0 0%	1 0.5%	2 0.2%
Region of Enrollment (participants) [Number]
France	11 5.1%	24 11.1%	18 8.3%	10 4.6%	63 7.3%
United States	125 58.4%	118 54.4%	132 60.8%	137 63.1%	512 59.2%
Spain	14 6.5%	15 6.9%	12 5.5%	14 6.5%	55 6.4%
Germany	24 11.2%	20 9.2%	22 10.1%	18 8.3%	84 9.7%
United Kingdom	13 6.1%	17 7.8%	10 4.6%	15 6.9%	55 6.4%
Italy	27 12.6%	23 10.6%	23 10.6%	23 10.6%	96 11.1%
Hepatitis C Virus (HCV) RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.4 (0.69)	6.4 (0.64)	6.3 (0.68)	6.3 (0.65)	6.4 (0.66)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	45 21%	44 20.3%	49 22.6%	44 20.3%	182 21%
≥ 800,000 IU/mL	169 79%	173 79.7%	168 77.4%	173 79.7%	683 79%
HCV Genotype (participants) [Number]
Genotype 1a	144 67.3%	148 68.2%	146 67.3%	143 65.9%	581 67.2%
Genotype 1b	66 30.8%	68 31.3%	68 31.3%	71 32.7%	273 31.6%
Genotype 1 (no confirmed subtype)	1 0.5%	1 0.5%	1 0.5%	1 0.5%	4 0.5%
Genotype 4	1 0.5%	0 0%	0 0%	1 0.5%	2 0.2%
Missing	2 0.9%	0 0%	2 0.9%	1 0.5%	5 0.6%
IL28b Status (participants) [Number]
CC	55 25.7%	76 35%	52 24%	73 33.6%	256 29.6%
CT	113 52.8%	107 49.3%	119 54.8%	112 51.6%	451 52.1%
TT	46 21.5%	34 15.7%	46 21.2%	32 14.7%	158 18.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Study Drug (SVR12)
Description	SVR12 was defined as HCV RNA level < the lower limit of quantification (LLOQ, ie, < 25 copies/mL) 12 weeks after last dose of study drug.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants were randomized and received at least 1 dose of study drug.

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	214	217	217	217
Number [percentage of participants]	98.6 46.1%	97.2 44.8%	98.2 45.3%	99.1 45.7%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 12 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF 12 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 12 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF+RBV 12 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 24 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF 24 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 24 Weeks
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF+RBV 24 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

2. Primary Outcome

Title	Incidence of Adverse Events Leading to Permanent Discontinuation From Any Study Drug
Description	The percentage of participants who experienced an adverse event leading to permanent discontinuation from any study drug was summarized.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set: participants were randomized and received at least 1 dose of study drug.

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	214	217	217	217
Number [percentage of participants]	0 0%	0.5 0.2%	1.8 0.8%	3.7 1.7%

3. Secondary Outcome

Title	Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Study Drug
Description	SVR4 and SVR24 were defined as HCV RNA level < LLOQ at 4 and 24 weeks after discontinuation of study drug, respectively.
Time Frame	Posttreatment Weeks 4 and 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	214	217	217	217
SVR4	98.6 46.1%	98.2 45.3%	99.1 45.7%	99.1 45.7%
SVR24	98.6 46.1%	97.2 44.8%	98.2 45.3%	99.1 45.7%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 2
Time Frame	Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	217	216	217
Number [percentage of participants]	82.2 38.4%	83.4 38.4%	82.9 38.2%	82.9 38.2%

5. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 4
Time Frame	Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	217	216	217
Number [percentage of participants]	100 46.7%	99.1 45.7%	100 46.1%	100 46.1%

6. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 8
Time Frame	Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	215	215	217
Number [percentage of participants]	99.5 46.5%	100 46.1%	99.5 45.9%	100 46.1%

7. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 2
Time Frame	Baseline; Week 2

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	217	216	216
Mean (Standard Deviation) [log10 IU/mL]	-4.90 (0.657)	-4.94 (0.633)	-4.86 (0.670)	-4.89 (0.648)

8. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 4
Time Frame	Baseline; Week 4

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	216	216	217
Mean (Standard Deviation) [log10 IU/mL]	-4.99 (0.697)	-5.02 (0.623)	-4.93 (0.678)	-4.96 (0.651)

9. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 8
Time Frame	Baseline; Week 8

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	213	215	216	217
Mean (Standard Deviation) [log10 IU/mL]	-4.99 (0.696)	-5.02 (0.625)	-4.91 (0.702)	-4.96 (0.651)

10. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	On-treatment virologic failure was defined as: Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow- up values, OR Rebound: > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (second confirmation value could have been posttreatment), or last available on-treatment measurement with no subsequent follow-up values, OR Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment Virologic relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement
Time Frame	Baseline to posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks	LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks	LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
Measure Participants	214	217	217	217
On-treatment virologic failure	0 0%	0 0%	0.5 0.2%	0 0%
Virologic relapse	0.5 0.2%	0 0%	0.5 0.2%	0 0%

Adverse Events

Time Frame	Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants were randomized and received at least 1 dose of study drug.
Arm/Group Title	LDV/SOF 12 Weeks		LDV/SOF+RBV 12 Weeks		LDV/SOF 24 Weeks		LDV/SOF+RBV 24 Weeks
Arm/Group Description	LDV/SOF 90/400 mg FDC tablet once daily for 12 weeks		LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 12 weeks		LDV/SOF 90/400 mg FDC tablet once daily for 24 weeks		LDV/SOF 90/400 mg FDC tablet once daily plus RBV tablets (1000 to 1200 mg daily based on weight) in a divided daily dose for 24 weeks
All Cause Mortality
	LDV/SOF 12 Weeks		LDV/SOF+RBV 12 Weeks		LDV/SOF 24 Weeks		LDV/SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LDV/SOF 12 Weeks		LDV/SOF+RBV 12 Weeks		LDV/SOF 24 Weeks		LDV/SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/214 (0.5%)		7/217 (3.2%)		18/217 (8.3%)		7/217 (3.2%)
Blood and lymphatic system disorders
Anaemia	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		0/217 (0%)
Factor VIII inhibition	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Lymphadenopathy	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Gastrointestinal disorders
Abdominal discomfort	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Colitis	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Mesenteric vein thrombosis	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
General disorders
Chest pain	1/214 (0.5%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Non-cardiac chest pain	0/214 (0%)		1/217 (0.5%)		1/217 (0.5%)		0/217 (0%)
Infections and infestations
Cellulitis	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		1/217 (0.5%)
Gastroenteritis	0/214 (0%)		0/217 (0%)		2/217 (0.9%)		0/217 (0%)
Pneumonia	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		1/217 (0.5%)
Progressive multifocal leukoencephalopathy	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Salpingitis	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Urinary tract infection	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Injury, poisoning and procedural complications
Hand fracture	0/214 (0%)		0/217 (0%)		2/217 (0.9%)		0/217 (0%)
Alcohol poisoning	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Concussion	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Fall	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Foot fracture	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Lower limb fracture	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Rib fracture	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Tibia fracture	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		0/217 (0%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		0/217 (0%)
Lumbar spinal stenosis	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Nervous system disorders
Carotid artery stenosis	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Headache	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Migraine	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		0/217 (0%)
Psychiatric disorders
Alcohol withdrawal syndrome	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Depression	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Substance abuse	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Renal and urinary disorders
Calculus ureteric	0/214 (0%)		0/217 (0%)		0/217 (0%)		1/217 (0.5%)
Reproductive system and breast disorders
Breast mass	0/214 (0%)		0/217 (0%)		1/217 (0.5%)		0/217 (0%)
Vascular disorders
Hypertension	0/214 (0%)		1/217 (0.5%)		0/217 (0%)		0/217 (0%)
Other (Not Including Serious) Adverse Events
	LDV/SOF 12 Weeks		LDV/SOF+RBV 12 Weeks		LDV/SOF 24 Weeks		LDV/SOF+RBV 24 Weeks
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	140/214 (65.4%)		168/217 (77.4%)		149/217 (68.7%)		189/217 (87.1%)
Blood and lymphatic system disorders
Anaemia	0/214 (0%)		25/217 (11.5%)		0/217 (0%)		22/217 (10.1%)
Gastrointestinal disorders
Nausea	24/214 (11.2%)		37/217 (17.1%)		29/217 (13.4%)		32/217 (14.7%)
Diarrhoea	24/214 (11.2%)		18/217 (8.3%)		24/217 (11.1%)		14/217 (6.5%)
Constipation	13/214 (6.1%)		12/217 (5.5%)		15/217 (6.9%)		10/217 (4.6%)
Dyspepsia	7/214 (3.3%)		11/217 (5.1%)		14/217 (6.5%)		12/217 (5.5%)
Abdominal pain	12/214 (5.6%)		9/217 (4.1%)		7/217 (3.2%)		8/217 (3.7%)
Vomiting	7/214 (3.3%)		9/217 (4.1%)		6/217 (2.8%)		12/217 (5.5%)
Abdominal pain upper	5/214 (2.3%)		11/217 (5.1%)		7/217 (3.2%)		9/217 (4.1%)
Gastrooesophageal reflux disease	4/214 (1.9%)		7/217 (3.2%)		3/217 (1.4%)		11/217 (5.1%)
General disorders
Fatigue	46/214 (21.5%)		79/217 (36.4%)		53/217 (24.4%)		84/217 (38.7%)
Asthenia	14/214 (6.5%)		23/217 (10.6%)		20/217 (9.2%)		26/217 (12%)
Irritability	11/214 (5.1%)		17/217 (7.8%)		17/217 (7.8%)		24/217 (11.1%)
Infections and infestations
Nasopharyngitis	14/214 (6.5%)		9/217 (4.1%)		13/217 (6%)		19/217 (8.8%)
Metabolism and nutrition disorders
Decreased appetite	10/214 (4.7%)		12/217 (5.5%)		8/217 (3.7%)		9/217 (4.1%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/214 (4.2%)		14/217 (6.5%)		21/217 (9.7%)		13/217 (6%)
Myalgia	9/214 (4.2%)		13/217 (6%)		12/217 (5.5%)		12/217 (5.5%)
Back pain	12/214 (5.6%)		5/217 (2.3%)		12/217 (5.5%)		14/217 (6.5%)
Muscle spasms	7/214 (3.3%)		14/217 (6.5%)		9/217 (4.1%)		12/217 (5.5%)
Nervous system disorders
Headache	54/214 (25.2%)		50/217 (23%)		54/217 (24.9%)		66/217 (30.4%)
Dizziness	11/214 (5.1%)		10/217 (4.6%)		14/217 (6.5%)		18/217 (8.3%)
Psychiatric disorders
Insomnia	17/214 (7.9%)		45/217 (20.7%)		26/217 (12%)		46/217 (21.2%)
Anxiety	7/214 (3.3%)		9/217 (4.1%)		12/217 (5.5%)		19/217 (8.8%)
Depression	5/214 (2.3%)		6/217 (2.8%)		5/217 (2.3%)		11/217 (5.1%)
Respiratory, thoracic and mediastinal disorders
Cough	6/214 (2.8%)		22/217 (10.1%)		16/217 (7.4%)		25/217 (11.5%)
Dyspnoea	3/214 (1.4%)		18/217 (8.3%)		5/217 (2.3%)		15/217 (6.9%)
Dyspnoea exertional	3/214 (1.4%)		9/217 (4.1%)		2/217 (0.9%)		11/217 (5.1%)
Skin and subcutaneous tissue disorders
Rash	16/214 (7.5%)		21/217 (9.7%)		16/217 (7.4%)		26/217 (12%)
Pruritus	11/214 (5.1%)		22/217 (10.1%)		8/217 (3.7%)		20/217 (9.2%)
Dry skin	2/214 (0.9%)		14/217 (6.5%)		3/217 (1.4%)		13/217 (6%)

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