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

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ClinicalTrials.gov Identifier: NCT01768286

Recruitment Status : Completed

First Posted : January 15, 2013

Results First Posted : November 26, 2014

Last Update Posted : November 16, 2018

Sponsor:

Information provided by (Responsible Party):

Gilead Sciences

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition	Chronic Hepatitis C Virus
Interventions	Drug: LDV/SOF Drug: RBV
Enrollment	441

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 Details	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 (...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Reason Not Completed
Randomized But Not Treated	0	0	1	0
Lack of Efficacy	7	4	0	1
Withdrew Consent	0	0	1	0

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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	Total of all reporting groups
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 Number of Baseline Participants		109	111	109	111	440
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Safety Analysis Set: participants were randomized and received at least one dose of study drug. Participants failed a previous HCV treatment regimen consisting of pegylated interferon alfa-2a (Pegasys) or pegylated interferon alfa-2b (Pegintron) plus ribavirin (RBV), with or without a protease inhibitor (PI).
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
		56 (6.9)	57 (8.0)	56 (8.3)	55 (7.8)	56 (7.8)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
	Female	35 32.1%	40 36.0%	35 32.1%	43 38.7%	153 34.8%
	Male	74 67.9%	71 64.0%	74 67.9%	68 61.3%	287 65.2%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
Black or African American		24	16	17	20	77
White		84	94	91	89	358
Asian		1	0	0	0	1
Hawaiian or Pacific Islander		0	1	0	1	2
Other		0	0	1	1	2
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
Hispanic/Latino		7	12	11	11	41
Not Hispanic or Latino		100	99	98	99	396
Not Disclosed		2	0	0	1	3
HCV RNA Mean (Standard Deviation) Unit of measure: Log10 IU/mL
	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
		6.5 (0.44)	6.4 (0.54)	6.4 (0.57)	6.5 (0.60)	6.5 (0.54)
HCV RNA Category Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
< 800,000 IU/mL		6	13	16	15	50
≥ 800,000 IU/mL		103	98	93	96	390
HCV Genotype Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
Genotype 1a		86	88	85	88	347
Genotype 1b		23	23	24	23	93
IL28b Status ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
CC		10	11	16	18	55
CT		70	77	68	68	283
TT		29	23	25	25	102
		[1] Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.
Prior HCV Treatment ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	109 participants	111 participants	109 participants	111 participants	440 participants
PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV		43	47	58	59	207
PI+PEG-IFN-alfa-2a or PEG-IFN-alfa-2b+RBV		66	64	50	51	231
IFN-alfa-2b+RBV		0	0	1	1	2
		[1] Measure Description: IFN-alfa-2b = interferon-alfa 2b; PEG-IFN-alfa-2a = pegylated interferon alfa-2a; PEG-IFN-alfa-2b - pegylated interferon alfa-2b; RBV = ribavirin; PI = protease inhibitor

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 (LLO...
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
	93.6	96.4	99.1	99.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 12 Weeks
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 12 Weeks
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 24 Weeks
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

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	[Not Specified]

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 24 Weeks
	Comments	[Not Specified]
	Type of Statistical Test	Superiority or Other
	Comments	[Not Specified]

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	[Not Specified]

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 leadin...
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
	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 fol...
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
SVR4	94.5	96.4	100.0	99.1
SVR24	93.6	96.4	99.1	99.1

4.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 1
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
	26.6	33.3	20.2	29.7

5.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 2
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
	81.7	82.9	81.7	83.8

6.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 4
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
	100.0	99.1	99.1	99.1

7.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 8
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	110
Measure Type: Number Unit of Measure: percentage of participants
	100.0	100.0	100.0	100.0

8.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 12
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	110
Measure Type: Number Unit of Measure: percentage of participants
	99.1	100.0	100.0	100.0

9.Secondary Outcome


Title	Percentage of Participants With HCV RNA < LLOQ at Week 24
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	0	0	107	110
Measure Type: Number Unit of Measure: percentage of participants
			100.0	100.0

10.Secondary Outcome


Title	Change From Baseline in HCV RNA at Week 1
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	108	111	109	110
Mean (Standard Deviation) Unit of Measure: 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
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Mean (Standard Deviation) Unit of Measure: 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
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Mean (Standard Deviation) Unit of Measure: 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
Description	[Not Specified]
Description	[Not Specified]
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	110
Mean (Standard Deviation) Unit of Measure: 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 de...
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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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
Overall Number of Participants Analyzed	109	111	109	111
Measure Type: Number Unit of Measure: percentage of participants
On-Treatment Virologic Failure	0	0	0	0.9
Virologic relapse	6.5	3.6	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 onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...	LDV 90 mg/SOF 400 mg FDC tablet onc...
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 (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	--/--	--/--	--/--	--/--
Serious Adverse Events Serious Adverse Events
	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	0/109 (0.00%)	0/111 (0.00%)	6/109 (5.50%)	3/111 (2.70%)
Cardiac disorders
Angina unstable ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Gastrointestinal disorders
Upper gastrointestinal haemorrhage ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
General disorders
Non-cardiac chest pain ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Hepatobiliary disorders
Cholecystitis acute ^† 1	0/109 (0.00%)	0/111 (0.00%)	0/109 (0.00%)	1/111 (0.90%)
Infections and infestations
Wound infection ^† 1	0/109 (0.00%)	0/111 (0.00%)	0/109 (0.00%)	1/111 (0.90%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Spondylolisthesis ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Nervous system disorders
Convulsion ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Hepatic encephalopathy ^† 1	0/109 (0.00%)	0/111 (0.00%)	1/109 (0.92%)	0/111 (0.00%)
Reproductive system and breast disorders
Vaginal prolapse ^† 1	0/109 (0.00%)	0/111 (0.00%)	0/109 (0.00%)	1/111 (0.90%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (16.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	LDV/SOF 12 Weeks	LDV/SOF+RBV 12 Weeks	LDV/SOF 24 Weeks	LDV/SOF+RBV 24 Weeks
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	73/109 (66.97%)	96/111 (86.49%)	87/109 (79.82%)	100/111 (90.09%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/109 (0.00%)	9/111 (8.11%)	1/109 (0.92%)	12/111 (10.81%)
Gastrointestinal disorders
Nausea ^† 1	13/109 (11.93%)	20/111 (18.02%)	7/109 (6.42%)	25/111 (22.52%)
Diarrhoea ^† 1	7/109 (6.42%)	5/111 (4.50%)	9/109 (8.26%)	17/111 (15.32%)
Constipation ^† 1	2/109 (1.83%)	4/111 (3.60%)	6/109 (5.50%)	3/111 (2.70%)
Vomiting ^† 1	2/109 (1.83%)	3/111 (2.70%)	0/109 (0.00%)	9/111 (8.11%)
Abdominal pain ^† 1	6/109 (5.50%)	2/111 (1.80%)	0/109 (0.00%)	5/111 (4.50%)
General disorders
Fatigue ^† 1	23/109 (21.10%)	45/111 (40.54%)	26/109 (23.85%)	50/111 (45.05%)
Irritability ^† 1	2/109 (1.83%)	13/111 (11.71%)	4/109 (3.67%)	12/111 (10.81%)
Infections and infestations
Upper respiratory tract infection ^† 1	4/109 (3.67%)	6/111 (5.41%)	7/109 (6.42%)	11/111 (9.91%)
Bronchitis ^† 1	2/109 (1.83%)	3/111 (2.70%)	4/109 (3.67%)	8/111 (7.21%)
Nasopharyngitis ^† 1	3/109 (2.75%)	5/111 (4.50%)	3/109 (2.75%)	6/111 (5.41%)
Sinusitis ^† 1	1/109 (0.92%)	6/111 (5.41%)	3/109 (2.75%)	7/111 (6.31%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	7/109 (6.42%)	13/111 (11.71%)	7/109 (6.42%)	17/111 (15.32%)
Myalgia ^† 1	5/109 (4.59%)	6/111 (5.41%)	8/109 (7.34%)	10/111 (9.01%)
Muscle spasms ^† 1	1/109 (0.92%)	8/111 (7.21%)	2/109 (1.83%)	12/111 (10.81%)
Back pain ^† 1	3/109 (2.75%)	3/111 (2.70%)	4/109 (3.67%)	10/111 (9.01%)
Nervous system disorders
Headache ^† 1	28/109 (25.69%)	26/111 (23.42%)	25/109 (22.94%)	35/111 (31.53%)
Dizziness ^† 1	3/109 (2.75%)	8/111 (7.21%)	7/109 (6.42%)	12/111 (10.81%)
Psychiatric disorders
Insomnia ^† 1	10/109 (9.17%)	18/111 (16.22%)	4/109 (3.67%)	19/111 (17.12%)
Anxiety ^† 1	2/109 (1.83%)	7/111 (6.31%)	4/109 (3.67%)	3/111 (2.70%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	5/109 (4.59%)	16/111 (14.41%)	5/109 (4.59%)	16/111 (14.41%)
Dyspnoea ^† 1	0/109 (0.00%)	16/111 (14.41%)	3/109 (2.75%)	9/111 (8.11%)
Nasal congestion ^† 1	6/109 (5.50%)	3/111 (2.70%)	1/109 (0.92%)	3/111 (2.70%)
Dyspnoea exertional ^† 1	0/109 (0.00%)	5/111 (4.50%)	0/109 (0.00%)	6/111 (5.41%)
Oropharyngeal pain ^† 1	1/109 (0.92%)	3/111 (2.70%)	0/109 (0.00%)	6/111 (5.41%)
Skin and subcutaneous tissue disorders
Rash ^† 1	2/109 (1.83%)	11/111 (9.91%)	6/109 (5.50%)	16/111 (14.41%)
Pruritus ^† 1	5/109 (4.59%)	10/111 (9.01%)	2/109 (1.83%)	10/111 (9.01%)
Dry skin ^† 1	0/109 (0.00%)	3/111 (2.70%)	3/109 (2.75%)	11/111 (9.91%)
† Indicates events were collected by systematic assessment 1 Term from vocabulary, MedDRA (16.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

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

Results Point of Contact

Name/Title: Clinical Trial Disclosures

Organization: Gilead Sciences, Inc.

EMail: ClinicalTrialDisclosures@gilead.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Grebely J, Mauss S, Brown A, Bronowicki JP, Puoti M, Wyles D, Natha M, Zhu Y, Yang J, Kreter B, Brainard DM, Yun C, Carr V, Dore GJ. Efficacy and Safety of Ledipasvir/Sofosbuvir With and Without Ribavirin in Patients With Chronic HCV Genotype 1 Infection Receiving Opioid Substitution Therapy: Analysis of Phase 3 ION Trials. Clin Infect Dis. 2016 Dec 1;63(11):1405-1411. Epub 2016 Aug 23.

Afdhal N, Reddy KR, Nelson DR, Lawitz E, Gordon SC, Schiff E, Nahass R, Ghalib R, Gitlin N, Herring R, Lalezari J, Younes ZH, Pockros PJ, Di Bisceglie AM, Arora S, Subramanian GM, Zhu Y, Dvory-Sobol H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Sulkowski M, Kwo P; ION-2 Investigators. Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection. N Engl J Med. 2014 Apr 17;370(16):1483-93. doi: 10.1056/NEJMoa1316366. Epub 2014 Apr 11.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01768286 History of Changes
Other Study ID Numbers:	GS-US-337-0109
First Submitted:	January 10, 2013
First Posted:	January 15, 2013
Results First Submitted:	November 21, 2014
Results First Posted:	November 26, 2014
Last Update Posted:	November 16, 2018

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