ION-2: Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin in Treatment-Experienced Subjects With Genotype 1 HCV Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01768286
• Collaborator: (none)
• Enrollment: 441
• Locations: 53
• Arms: 4
• Duration (Months): 13
• Patients Per Site: 8.3
• Patients Per Site Per Month: 0.6

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir fixed dose combination (FDC) with or without ribavirin (RBV) administered for 12 or 24 weeks in treatment-experienced subjects with chronic genotype 1 hepatitis C virus (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: 441 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 ± Ribavirin for 12 and 24 Weeks in Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection
• Study Start Date: Jan 1, 2013
• Actual Primary Completion Date: Nov 1, 2013
• Actual Study Completion Date: Feb 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF 12 Weeks Participants will receive LDV/SOF FDC for 12 weeks.	Drug: LDV/SOF; Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7997
Experimental: LDV/SOF+RBV 12 Weeks Participants will receive LDV/SOF FDC plus RBV for 12 weeks.	Drug: LDV/SOF; Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7997 ; Drug: RBV; Ribavirin (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 Participants will receive LDV/SOF FDC for 24 weeks.	Drug: LDV/SOF; Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7997
Experimental: LDV/SOF+RBV 24 Weeks Participants will receive LDV/SOF FDC plus RBV for 24 weeks.	Drug: LDV/SOF; Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7997 ; Drug: RBV; Ribavirin (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 Therapy (SVR12) [Posttreatment Week 12]

   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks following the 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 Therapy (SVR4 and SVR24) [Posttreatment Weeks 4 and 24]

   SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.

2. Percentage of Participants With HCV RNA < LLOQ at Week 1 [Week 1]

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

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

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

6. Percentage of Participants With HCV RNA < LLOQ at Week 12 [Week 12]

7. Percentage of Participants With HCV RNA < LLOQ at Week 24 [Week 24]

8. Change From Baseline in HCV RNA at Week 1 [Baseline; Week 1]

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

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

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

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

    Virologic failure was defined as on-treatment virologic failure or virologic relapse. On-Treatment Virologic Failure was defined as 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 was defined as 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

Inclusion Criteria:

• Age > 18, with chronic genotype 1 HCV infection

• HCV treatment-experienced, including patients who have previously failed a nonstructural protein (NS)3/4A protease inhibitor plus pegylated interferon (PEG)/RBV regimen

• 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

• Coinfection with HIV or hepatitis B virus

• Current or prior history of clinical hepatic decompensation

• Hepatocellular carcinoma 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		Phoenix	Arizona	United States
2		Tucson	Arizona	United States
3		La Jolla	California	United States
4		Los Angeles	California	United States
5		Palo Alto	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		Jacksonville	Florida	United States
13		Miami	Florida	United States
14		Orlando	Florida	United States
15		Atlanta	Georgia	United States
16		Marietta	Georgia	United States
17		Chicago	Illinois	United States
18		Indianapolis	Indiana	United States
19		Bowling Green	Kentucky	United States
20		Baton Rouge	Louisiana	United States
21		Baltimore	Maryland	United States
22		Lutherville	Maryland	United States
23		Boston	Massachusetts	United States
24		Springfield	Massachusetts	United States
25		Detroit	Michigan	United States
26		Rochester	Minnesota	United States
27		Saint Louis	Minnesota	United States
28		Saint Paul	Minnesota	United States
29		Kansas City	Missouri	United States
30		Berlin	New Jersey	United States
31		Hillsborough	New Jersey	United States
32		Albuquerque	New Mexico	United States
33		Santa Fe	New Mexico	United States
34		Binghamton	New York	United States
35		Manhasset	New York	United States
36		New York	New York	United States
37		Asheville	North Carolina	United States
38		Charlotte	North Carolina	United States
39		Durham	North Carolina	United States
40		Fayetteville	North Carolina	United States
41		Statesville	North Carolina	United States
42		Winston-Salem	North Carolina	United States
43		Philadelphia	Pennsylvania	United States
44		Providence	Rhode Island	United States
45		Germantown	Tennessee	United States
46		Nashville	Tennessee	United States
47		Arlington	Texas	United States
48		Dallas	Texas	United States
49		Houston	Texas	United States
50		San Antonio	Texas	United States
51		Fairfax	Virginia	United States
52		Newport News	Virginia	United States
53		Norfolk	Virginia	United States

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Jenny Yang, PharmD, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01768286
• Other Study ID Numbers: GS-US-337-0109
• First Posted: Jan 15, 2013
• Last Update Posted: Nov 16, 2018
• Last Verified: Nov 1, 2014

• 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: Infections; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 64 study sites in the United States. The first participant was screened on 03 January 2013. The last participant observation occurred on 20 February 2014.
Pre-assignment Detail	551 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 (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus ribavirin (RBV) tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Period Title: Overall Study
STARTED	109	111	110	111
COMPLETED	102	107	108	110
NOT COMPLETED	7	4	2	1

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks	Total of all reporting groups
Overall Participants	109	111	109	111	440
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (6.9)	57 (8.0)	56 (8.3)	55 (7.8)	56 (7.8)
Sex: Female, Male (Count of Participants)
Female	35 32.1%	40 36%	35 32.1%	43 38.7%	153 34.8%
Male	74 67.9%	71 64%	74 67.9%	68 61.3%	287 65.2%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	24 22%	16 14.4%	17 15.6%	20 18%	77 17.5%
White	84 77.1%	94 84.7%	91 83.5%	89 80.2%	358 81.4%
Asian	1 0.9%	0 0%	0 0%	0 0%	1 0.2%
Hawaiian or Pacific Islander	0 0%	1 0.9%	0 0%	1 0.9%	2 0.5%
Other	0 0%	0 0%	1 0.9%	1 0.9%	2 0.5%
Race/Ethnicity, Customized (participants) [Number]
Hispanic/Latino	7 6.4%	12 10.8%	11 10.1%	11 9.9%	41 9.3%
Not Hispanic or Latino	100 91.7%	99 89.2%	98 89.9%	99 89.2%	396 90%
Not Disclosed	2 1.8%	0 0%	0 0%	1 0.9%	3 0.7%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.5 (0.44)	6.4 (0.54)	6.4 (0.57)	6.5 (0.60)	6.5 (0.54)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	6 5.5%	13 11.7%	16 14.7%	15 13.5%	50 11.4%
≥ 800,000 IU/mL	103 94.5%	98 88.3%	93 85.3%	96 86.5%	390 88.6%
HCV Genotype (participants) [Number]
Genotype 1a	86 78.9%	88 79.3%	85 78%	88 79.3%	347 78.9%
Genotype 1b	23 21.1%	23 20.7%	24 22%	23 20.7%	93 21.1%
IL28b Status (participants) [Number]
CC	10 9.2%	11 9.9%	16 14.7%	18 16.2%	55 12.5%
CT	70 64.2%	77 69.4%	68 62.4%	68 61.3%	283 64.3%
TT	29 26.6%	23 20.7%	25 22.9%	25 22.5%	102 23.2%
Prior HCV Treatment (participants) [Number]
PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV	43 39.4%	47 42.3%	58 53.2%	59 53.2%	207 47%
PI+PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV	66 60.6%	64 57.7%	50 45.9%	51 45.9%	231 52.5%
IFN-alfa-2b+RBV	0 0%	0 0%	1 0.9%	1 0.9%	2 0.5%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Description	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks following the last dose of study drug.
Time Frame	Posttreatment Week 12

Outcome Measure Data

Analysis Population Description

Full Analysis Set: participants who were randomized and received at least one 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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Number [percentage of participants]	93.6 85.9%	96.4 86.8%	99.1 90.9%	99.1 89.3%

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	A 2-sided 1-sample binomial test was used to compare over the historical SVR12 rate of 25%. To control the family-wise type I error rate at 0.05, the Hochberg procedure was applied, from which the adjusted p-values were obtained.
	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	A 2-sided 1-sample binomial test was used to compare over the historical SVR12 rate of 25%. To control the family-wise type I error rate at 0.05, the Hochberg procedure was applied, from which the adjusted p-values were obtained.
	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	A 2-sided 1-sample binomial test was used to compare over the historical SVR12 rate of 25%. To control the family-wise type I error rate at 0.05, the Hochberg procedure was applied, from which the adjusted p-values were obtained.
	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	A 2-sided 1-sample binomial test was used to compare over the historical SVR12 rate of 25%. To control the family-wise type I error rate at 0.05, the Hochberg procedure was applied, from which the adjusted p-values were obtained.
	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

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Number [percentage of participants]	0 0%	0 0%	0 0%	0 0%

3. Secondary Outcome

Title	Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24)
Description	SVR4 and SVR24 were defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose 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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
SVR4	94.5 86.7%	96.4 86.8%	100.0 91.7%	99.1 89.3%
SVR24	93.6 85.9%	96.4 86.8%	99.1 90.9%	99.1 89.3%

4. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 1
Time Frame	Week 1

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Number [percentage of participants]	26.6 24.4%	33.3 30%	20.2 18.5%	29.7 26.8%

5. Secondary Outcome

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

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Number [percentage of participants]	81.7 75%	82.9 74.7%	81.7 75%	83.8 75.5%

6. Secondary Outcome

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

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Number [percentage of participants]	100.0 91.7%	99.1 89.3%	99.1 90.9%	99.1 89.3%

7. 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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	110
Number [percentage of participants]	100.0 91.7%	100.0 90.1%	100.0 91.7%	100.0 90.1%

8. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 12
Time Frame	Week 12

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	110
Number [percentage of participants]	99.1 90.9%	100.0 90.1%	100.0 91.7%	100.0 90.1%

9. Secondary Outcome

Title	Percentage of Participants With HCV RNA < LLOQ at Week 24
Time Frame	Week 24

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with available data were analyzed. Participants in the LDV/SOF 12 Weeks and LDV/SOF+RBV 12 Weeks groups did not continue treatment past Week 12 and are not included in the analysis.

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	0	0	107	110
Number [percentage of participants]	100.0 91.7%	100.0 90.1%

10. Secondary Outcome

Title	Change From Baseline in HCV RNA at Week 1
Time Frame	Baseline; Week 1

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	108	111	109	110
Mean (Standard Deviation) [log10 IU/mL]	-4.57 (0.501)	-4.50 (0.540)	-4.47 (0.569)	-4.50 (0.575)

11. Secondary Outcome

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

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Mean (Standard Deviation) [log10 IU/mL]	-5.08 (0.443)	-4.94 (0.520)	-4.99 (0.571)	-4.99 (0.617)

12. Secondary Outcome

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

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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
Mean (Standard Deviation) [log10 IU/mL]	-5.16 (0.439)	-5.02 (0.543)	-5.06 (0.571)	-5.04 (0.779)

13. 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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	110
Mean (Standard Deviation) [log10 IU/mL]	-5.16 (0.439)	-5.02 (0.544)	-5.06 (0.571)	-5.08 (0.605)

14. Secondary Outcome

Title	Percentage of Participants With Virologic Failure
Description	Virologic failure was defined as on-treatment virologic failure or virologic relapse. On-Treatment Virologic Failure was defined as 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 was defined as confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 24 weeks
Measure Participants	109	111	109	111
On-Treatment Virologic Failure	0 0%	0 0%	0 0%	0.9 0.8%
Virologic relapse	6.5 6%	3.6 3.2%	0 0%	0 0%

Adverse Events

Time Frame	Up to 24 weeks plus 30 days
Adverse Event Reporting Description	Safety 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 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks		LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) for 12 weeks		LDV 90 mg/SOF 400 mg FDC tablet once daily for 24 weeks		LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000-1200 mg daily based on weight) 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	0/109 (0%)		0/111 (0%)		6/109 (5.5%)		3/111 (2.7%)
Cardiac disorders
Angina unstable	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
General disorders
Non-cardiac chest pain	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Hepatobiliary disorders
Cholecystitis acute	0/109 (0%)		0/111 (0%)		0/109 (0%)		1/111 (0.9%)
Infections and infestations
Wound infection	0/109 (0%)		0/111 (0%)		0/109 (0%)		1/111 (0.9%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Spondylolisthesis	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Nervous system disorders
Convulsion	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Hepatic encephalopathy	0/109 (0%)		0/111 (0%)		1/109 (0.9%)		0/111 (0%)
Reproductive system and breast disorders
Vaginal prolapse	0/109 (0%)		0/111 (0%)		0/109 (0%)		1/111 (0.9%)
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	73/109 (67%)		96/111 (86.5%)		87/109 (79.8%)		100/111 (90.1%)
Blood and lymphatic system disorders
Anaemia	0/109 (0%)		9/111 (8.1%)		1/109 (0.9%)		12/111 (10.8%)
Gastrointestinal disorders
Nausea	13/109 (11.9%)		20/111 (18%)		7/109 (6.4%)		25/111 (22.5%)
Diarrhoea	7/109 (6.4%)		5/111 (4.5%)		9/109 (8.3%)		17/111 (15.3%)
Constipation	2/109 (1.8%)		4/111 (3.6%)		6/109 (5.5%)		3/111 (2.7%)
Vomiting	2/109 (1.8%)		3/111 (2.7%)		0/109 (0%)		9/111 (8.1%)
Abdominal pain	6/109 (5.5%)		2/111 (1.8%)		0/109 (0%)		5/111 (4.5%)
General disorders
Fatigue	23/109 (21.1%)		45/111 (40.5%)		26/109 (23.9%)		50/111 (45%)
Irritability	2/109 (1.8%)		13/111 (11.7%)		4/109 (3.7%)		12/111 (10.8%)
Infections and infestations
Upper respiratory tract infection	4/109 (3.7%)		6/111 (5.4%)		7/109 (6.4%)		11/111 (9.9%)
Bronchitis	2/109 (1.8%)		3/111 (2.7%)		4/109 (3.7%)		8/111 (7.2%)
Nasopharyngitis	3/109 (2.8%)		5/111 (4.5%)		3/109 (2.8%)		6/111 (5.4%)
Sinusitis	1/109 (0.9%)		6/111 (5.4%)		3/109 (2.8%)		7/111 (6.3%)
Musculoskeletal and connective tissue disorders
Arthralgia	7/109 (6.4%)		13/111 (11.7%)		7/109 (6.4%)		17/111 (15.3%)
Myalgia	5/109 (4.6%)		6/111 (5.4%)		8/109 (7.3%)		10/111 (9%)
Muscle spasms	1/109 (0.9%)		8/111 (7.2%)		2/109 (1.8%)		12/111 (10.8%)
Back pain	3/109 (2.8%)		3/111 (2.7%)		4/109 (3.7%)		10/111 (9%)
Nervous system disorders
Headache	28/109 (25.7%)		26/111 (23.4%)		25/109 (22.9%)		35/111 (31.5%)
Dizziness	3/109 (2.8%)		8/111 (7.2%)		7/109 (6.4%)		12/111 (10.8%)
Psychiatric disorders
Insomnia	10/109 (9.2%)		18/111 (16.2%)		4/109 (3.7%)		19/111 (17.1%)
Anxiety	2/109 (1.8%)		7/111 (6.3%)		4/109 (3.7%)		3/111 (2.7%)
Respiratory, thoracic and mediastinal disorders
Cough	5/109 (4.6%)		16/111 (14.4%)		5/109 (4.6%)		16/111 (14.4%)
Dyspnoea	0/109 (0%)		16/111 (14.4%)		3/109 (2.8%)		9/111 (8.1%)
Nasal congestion	6/109 (5.5%)		3/111 (2.7%)		1/109 (0.9%)		3/111 (2.7%)
Dyspnoea exertional	0/109 (0%)		5/111 (4.5%)		0/109 (0%)		6/111 (5.4%)
Oropharyngeal pain	1/109 (0.9%)		3/111 (2.7%)		0/109 (0%)		6/111 (5.4%)
Skin and subcutaneous tissue disorders
Rash	2/109 (1.8%)		11/111 (9.9%)		6/109 (5.5%)		16/111 (14.4%)
Pruritus	5/109 (4.6%)		10/111 (9%)		2/109 (1.8%)		10/111 (9%)
Dry skin	0/109 (0%)		3/111 (2.7%)		3/109 (2.8%)		11/111 (9.9%)

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