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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT01701401

Recruitment Status : Completed

First Posted : October 5, 2012

Results First Posted : March 27, 2015

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	870

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 Details	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/...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Reason Not Completed
Randomized But Not Treated	3	1	0	1
Lost to Follow-up	5	5	1	3
Withdrew Consent	0	3	1	2
Lack of Efficacy	1	0	2	0
Adverse Event	1	0	0	0
Protocol Violation	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/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	Total of all reporting groups
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 Number of Baseline Participants		214	217	217	217	865
Baseline Analysis Population Description		...
Baseline Analysis Population Description		Safety Analysis Set: participants were randomized and received at least 1 dose of study drug.
Age, Continuous Mean (Standard Deviation) Unit of measure: Years
	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
		52 (10.7)	52 (11.5)	53 (10.3)	53 (9.9)	52 (10.6)
Sex: Female, Male Measure Type: Count of Participants Unit of measure: Participants
	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
	Female	87 40.7%	89 41.0%	78 35.9%	98 45.2%	352 40.7%
	Male	127 59.3%	128 59.0%	139 64.1%	119 54.8%	513 59.3%
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
Black or African American		24	26	32	26	108
White		187	188	177	183	735
Asian		1	0	5	5	11
American Indian/Alaska Native		0	1	0	1	2
Hawaiian or Pacific Islander		0	0	1	0	1
Other		2	1	2	1	6
Not Disclosed		0	1	0	1	2
Race/Ethnicity, Customized Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
Hispanic or Latino		26	20	29	26	101
Not Hispanic or Latino		187	197	188	190	762
Not Disclosed		1	0	0	1	2
Region of Enrollment Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
France		11	24	18	10	63
United States		125	118	132	137	512
Spain		14	15	12	14	55
Germany		24	20	22	18	84
United Kingdom		13	17	10	15	55
Italy		27	23	23	23	96
Hepatitis C Virus (HCV) RNA Mean (Standard Deviation) Unit of measure: Log10 IU/mL
	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
		6.4 (0.69)	6.4 (0.64)	6.3 (0.68)	6.3 (0.65)	6.4 (0.66)
HCV RNA Category Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
< 800,000 IU/mL		45	44	49	44	182
≥ 800,000 IU/mL		169	173	168	173	683
HCV Genotype ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
Genotype 1a		144	148	146	143	581
Genotype 1b		66	68	68	71	273
Genotype 1 (no confirmed subtype)		1	1	1	1	4
Genotype 4		1	0	0	1	2
Missing		2	0	2	1	5
		[1] Measure Description: There are variations of HCV which are all similar enough to be called HCV, but are distinct enough to be referred to as HCV genotypes.
IL28b Status ^[1] Measure Type: Number Unit of measure: Participants	Number Analyzed	214 participants	217 participants	217 participants	217 participants	865 participants
CC		55	76	52	73	256
CT		113	107	119	112	451
TT		46	34	46	32	158
		[1] Measure Description: CC, CT, and TT alleles are different forms of the IL28b gene.

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 quantificat...
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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	214	217	217	217
Measure Type: Number Unit of Measure: percentage of participants
	98.6	97.2	98.2	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	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	[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	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	[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	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	[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	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	[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: 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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	214	217	217	217
Measure Type: Number Unit of Measure: percentage of participants
	0	0.5	1.8	3.7

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 wee...
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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	214	217	217	217
Measure Type: Number Unit of Measure: percentage of participants
SVR4	98.6	98.2	99.1	99.1
SVR24	98.6	97.2	98.2	99.1

4.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

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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	217	216	217
Measure Type: Number Unit of Measure: percentage of participants
	82.2	83.4	82.9	82.9

5.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

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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	217	216	217
Measure Type: Number Unit of Measure: percentage of participants
	100	99.1	100	100

6.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/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	215	215	217
Measure Type: Number Unit of Measure: percentage of participants
	99.5	100	99.5	100

7.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

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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	217	216	216
Mean (Standard Deviation) Unit of Measure: 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
Description	[Not Specified]
Description	[Not Specified]
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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	216	216	217
Mean (Standard Deviation) Unit of Measure: 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
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/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	213	215	216	217
Mean (Standard Deviation) Unit of Measure: 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 f...
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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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
Overall Number of Participants Analyzed	214	217	217	217
Measure Type: Number Unit of Measure: percentage of participants
On-treatment virologic failure	0	0	0.5	0
Virologic relapse	0.5	0	0.5	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 d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...	LDV/SOF 90/400 mg FDC tablet once d...
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 (%)	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	1/214 (0.47%)	7/217 (3.23%)	18/217 (8.29%)	7/217 (3.23%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	0/217 (0.00%)
Factor VIII inhibition ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Lymphadenopathy ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Gastrointestinal disorders
Abdominal discomfort ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Colitis ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Mesenteric vein thrombosis ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
General disorders
Chest pain ^† 1	1/214 (0.47%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Non-cardiac chest pain ^† 1	0/214 (0.00%)	1/217 (0.46%)	1/217 (0.46%)	0/217 (0.00%)
Infections and infestations
Cellulitis ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	1/217 (0.46%)
Gastroenteritis ^† 1	0/214 (0.00%)	0/217 (0.00%)	2/217 (0.92%)	0/217 (0.00%)
Pneumonia ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	1/217 (0.46%)
Progressive multifocal leukoencephalopathy ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Salpingitis ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Urinary tract infection ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Injury, poisoning and procedural complications
Hand fracture ^† 1	0/214 (0.00%)	0/217 (0.00%)	2/217 (0.92%)	0/217 (0.00%)
Alcohol poisoning ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Concussion ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Fall ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Foot fracture ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Lower limb fracture ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Rib fracture ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Tibia fracture ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	0/217 (0.00%)
Musculoskeletal and connective tissue disorders
Intervertebral disc protrusion ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	0/217 (0.00%)
Lumbar spinal stenosis ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Nervous system disorders
Carotid artery stenosis ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Headache ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Migraine ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	0/217 (0.00%)
Psychiatric disorders
Alcohol withdrawal syndrome ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Depression ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Substance abuse ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Renal and urinary disorders
Calculus ureteric ^† 1	0/214 (0.00%)	0/217 (0.00%)	0/217 (0.00%)	1/217 (0.46%)
Reproductive system and breast disorders
Breast mass ^† 1	0/214 (0.00%)	0/217 (0.00%)	1/217 (0.46%)	0/217 (0.00%)
Vascular disorders
Hypertension ^† 1	0/214 (0.00%)	1/217 (0.46%)	0/217 (0.00%)	0/217 (0.00%)
† 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	140/214 (65.42%)	168/217 (77.42%)	149/217 (68.66%)	189/217 (87.10%)
Blood and lymphatic system disorders
Anaemia ^† 1	0/214 (0.00%)	25/217 (11.52%)	0/217 (0.00%)	22/217 (10.14%)
Gastrointestinal disorders
Nausea ^† 1	24/214 (11.21%)	37/217 (17.05%)	29/217 (13.36%)	32/217 (14.75%)
Diarrhoea ^† 1	24/214 (11.21%)	18/217 (8.29%)	24/217 (11.06%)	14/217 (6.45%)
Constipation ^† 1	13/214 (6.07%)	12/217 (5.53%)	15/217 (6.91%)	10/217 (4.61%)
Dyspepsia ^† 1	7/214 (3.27%)	11/217 (5.07%)	14/217 (6.45%)	12/217 (5.53%)
Abdominal pain ^† 1	12/214 (5.61%)	9/217 (4.15%)	7/217 (3.23%)	8/217 (3.69%)
Vomiting ^† 1	7/214 (3.27%)	9/217 (4.15%)	6/217 (2.76%)	12/217 (5.53%)
Abdominal pain upper ^† 1	5/214 (2.34%)	11/217 (5.07%)	7/217 (3.23%)	9/217 (4.15%)
Gastrooesophageal reflux disease ^† 1	4/214 (1.87%)	7/217 (3.23%)	3/217 (1.38%)	11/217 (5.07%)
General disorders
Fatigue ^† 1	46/214 (21.50%)	79/217 (36.41%)	53/217 (24.42%)	84/217 (38.71%)
Asthenia ^† 1	14/214 (6.54%)	23/217 (10.60%)	20/217 (9.22%)	26/217 (11.98%)
Irritability ^† 1	11/214 (5.14%)	17/217 (7.83%)	17/217 (7.83%)	24/217 (11.06%)
Infections and infestations
Nasopharyngitis ^† 1	14/214 (6.54%)	9/217 (4.15%)	13/217 (5.99%)	19/217 (8.76%)
Metabolism and nutrition disorders
Decreased appetite ^† 1	10/214 (4.67%)	12/217 (5.53%)	8/217 (3.69%)	9/217 (4.15%)
Musculoskeletal and connective tissue disorders
Arthralgia ^† 1	9/214 (4.21%)	14/217 (6.45%)	21/217 (9.68%)	13/217 (5.99%)
Myalgia ^† 1	9/214 (4.21%)	13/217 (5.99%)	12/217 (5.53%)	12/217 (5.53%)
Back pain ^† 1	12/214 (5.61%)	5/217 (2.30%)	12/217 (5.53%)	14/217 (6.45%)
Muscle spasms ^† 1	7/214 (3.27%)	14/217 (6.45%)	9/217 (4.15%)	12/217 (5.53%)
Nervous system disorders
Headache ^† 1	54/214 (25.23%)	50/217 (23.04%)	54/217 (24.88%)	66/217 (30.41%)
Dizziness ^† 1	11/214 (5.14%)	10/217 (4.61%)	14/217 (6.45%)	18/217 (8.29%)
Psychiatric disorders
Insomnia ^† 1	17/214 (7.94%)	45/217 (20.74%)	26/217 (11.98%)	46/217 (21.20%)
Anxiety ^† 1	7/214 (3.27%)	9/217 (4.15%)	12/217 (5.53%)	19/217 (8.76%)
Depression ^† 1	5/214 (2.34%)	6/217 (2.76%)	5/217 (2.30%)	11/217 (5.07%)
Respiratory, thoracic and mediastinal disorders
Cough ^† 1	6/214 (2.80%)	22/217 (10.14%)	16/217 (7.37%)	25/217 (11.52%)
Dyspnoea ^† 1	3/214 (1.40%)	18/217 (8.29%)	5/217 (2.30%)	15/217 (6.91%)
Dyspnoea exertional ^† 1	3/214 (1.40%)	9/217 (4.15%)	2/217 (0.92%)	11/217 (5.07%)
Skin and subcutaneous tissue disorders
Rash ^† 1	16/214 (7.48%)	21/217 (9.68%)	16/217 (7.37%)	26/217 (11.98%)
Pruritus ^† 1	11/214 (5.14%)	22/217 (10.14%)	8/217 (3.69%)	20/217 (9.22%)
Dry skin ^† 1	2/214 (0.93%)	14/217 (6.45%)	3/217 (1.38%)	13/217 (5.99%)
† 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.

Younossi ZM, Elsheikh E, Stepanova M, Gerber L, Nader F, Stamm LM, Brainard DM, McHutchinson JG. Ledipasvir/sofosbuvir treatment of hepatitis C virus is associated with reduction in serum apolipoprotein levels. J Viral Hepat. 2015 Dec;22(12):977-82. doi: 10.1111/jvh.12448. Epub 2015 Aug 17.

Afdhal N, Zeuzem S, Kwo P, Chojkier M, Gitlin N, Puoti M, Romero-Gomez M, Zarski JP, Agarwal K, Buggisch P, Foster GR, Bräu N, Buti M, Jacobson IM, Subramanian GM, Ding X, Mo H, Yang JC, Pang PS, Symonds WT, McHutchison JG, Muir AJ, Mangia A, Marcellin P; ION-1 Investigators. Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection. N Engl J Med. 2014 May 15;370(20):1889-98. doi: 10.1056/NEJMoa1402454. Epub 2014 Apr 11.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01701401 History of Changes
Other Study ID Numbers:	GS-US-337-0102 2012-003387-43 ( EudraCT Number )
First Submitted:	October 2, 2012
First Posted:	October 5, 2012
Results First Submitted:	March 17, 2015
Results First Posted:	March 27, 2015
Last Update Posted:	November 16, 2018

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