Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed-Dose Combination ± Ribavirin for the Treatment of HCV (ION-3)

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01851330
• Collaborator: (none)
• Enrollment: 647
• Locations: 52
• Arms: 3
• Duration (Months): 10
• Patients Per Site: 12.4
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV) administered for 8 or 12 weeks in treatment-naive participants with chronic genotype 1 HCV infection.

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 647 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/Ledipasvir Fixed-Dose Combination ± Ribavirin for 8 Weeks and Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection
• Study Start Date: May 1, 2013
• Actual Primary Completion Date: Dec 1, 2013
• Actual Study Completion Date: Mar 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF 8 Week Participants will receive LDV/SOF FDC for 8 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977
Experimental: LDV/SOF+RBV 8 Week Participants will receive LDV/SOF FDC plus RBV for 8 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977 ; 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 12 Week Participants will receive LDV/SOF FDC for 12 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Names: Harvoni® GS-5885/GS-7977

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants With Sustained Virologic Response 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 12 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 Sustained Virologic Response 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 2 [Week 2]

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

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

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

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

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

8. Percentage of Participants Experiencing 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-naive

• HCV RNA > 10,000 IU/mL at screening

• 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

• Presence of cirrhosis

• Coinfection with HIV or hepatitis B virus (HBV)

• Current or prior history of clinical hepatic decompensation

• Chronic use of systemic immunosuppressive agents

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Birmingham	Alabama	United States
2		La Jolla	California	United States
3		Los Angeles	California	United States
4		Palo Alto	California	United States
5		Sacramento	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		Wellington	Florida	United States
16		Atlanta	Georgia	United States
17		Decatur	Georgia	United States
18		Marietta	Georgia	United States
19		Chicago	Illinois	United States
20		Indianapolis	Indiana	United States
21		Bowling Green	Kentucky	United States
22		Baton Rouge	Louisiana	United States
23		Baltimore	Maryland	United States
24		Lutherville	Maryland	United States
25		Boston	Massachusetts	United States
26		Novi	Michigan	United States
27		Kansas City	Missouri	United States
28		Saint Louis	Missouri	United States
29		Albuquerque	New Jersey	United States
30		Berlin	New Jersey	United States
31		Hillsborough	New Jersey	United States
32		Santa Fe	New Mexico	United States
33		Binghamton	New York	United States
34		Manhasset	New York	United States
35		New York	New York	United States
36		Chapel Hill	North Carolina	United States
37		Fayetteville	North Carolina	United States
38		Statesville	North Carolina	United States
39		Winston-Salem	North Carolina	United States
40		Philadelphia	Pennsylvania	United States
41		Providence	Rhode Island	United States
42		Germantown	Tennessee	United States
43		Nashville	Tennessee	United States
44		Arlington	Texas	United States
45		Houston	Texas	United States
46		San Antonio	Texas	United States
47		Fairfax	Virginia	United States
48		Falls Church	Virginia	United States
49		Newport News	Virginia	United States
50		Norfolk	Virginia	United States
51		Richmond	Virginia	United States
52		Seattle	Washington	United States

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Robert H. Hyland, DPhil, Gilead Sciences

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT01851330
• Other Study ID Numbers: GS-US-337-0108
• First Posted: May 10, 2013
• Last Update Posted: Nov 16, 2018
• Last Verified: Dec 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: Hepatitis C; Hepatitis C, Chronic; Hepatitis; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at a total of 59 study sites in the United States. The first participant was screened on 06 May 2013. The last participant observation occurred on 07 March 2014.
Pre-assignment Detail	831 participants were screened.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	Ledipasvir (LDV) 90 mg/sofosbuvir (SOF) 400 mg fixed-dose combination (FDC) tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus ribavirin (RBV) tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Period Title: Overall Study
STARTED	215	216	216
COMPLETED	202	200	204
NOT COMPLETED	13	16	12

Baseline Characteristics

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week	Total
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks	Total of all reporting groups
Overall Participants	215	216	216	647
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	53 (10.2)	51 (11.7)	53 (10.6)	52 (10.9)
Sex: Female, Male (Count of Participants)
Female	85 39.5%	99 45.8%	88 40.7%	272 42%
Male	130 60.5%	117 54.2%	128 59.3%	375 58%
Race/Ethnicity, Customized (participants) [Number]
Black or African American	45 20.9%	36 16.7%	42 19.4%	123 19%
White	164 76.3%	176 81.5%	167 77.3%	507 78.4%
Asian	5 2.3%	2 0.9%	3 1.4%	10 1.5%
American Indian/Alaska Native	0 0%	1 0.5%	0 0%	1 0.2%
Hawaiian or Pacific Islander	0 0%	1 0.5%	0 0%	1 0.2%
Other	1 0.5%	0 0%	3 1.4%	4 0.6%
Not Disclosed	0 0%	0 0%	1 0.5%	1 0.2%
Race/Ethnicity, Customized (participants) [Number]
Hispanic or Latino	13 6%	12 5.6%	14 6.5%	39 6%
Not Hispanic or Latino	200 93%	204 94.4%	202 93.5%	606 93.7%
Not Disclosed	2 0.9%	0 0%	0 0%	2 0.3%
HCV RNA (log10 IU/mL) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [log10 IU/mL]	6.5 (0.76)	6.4 (0.69)	6.4 (0.76)	6.5 (0.74)
HCV RNA Category (participants) [Number]
< 800,000 IU/mL	34 15.8%	45 20.8%	44 20.4%	123 19%
≥ 800,000 IU/mL	181 84.2%	171 79.2%	172 79.6%	524 81%
HCV Genotype (participants) [Number]
Genotype 1 (no confirmed subtype)	1 0.5%	0 0%	0 0%	1 0.2%
Genotype 1a	171 79.5%	172 79.6%	172 79.6%	515 79.6%
Genotype 1b	43 20%	44 20.4%	44 20.4%	131 20.2%
IL28b Status (participants) [Number]
CC	56 26%	60 27.8%	56 25.9%	172 26.6%
CT	120 55.8%	128 59.3%	124 57.4%	372 57.5%
TT	39 18.1%	28 13%	36 16.7%	103 15.9%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants With Sustained Virologic Response 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 were randomized and received at least one dose of study medication.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	216	216
Number [percentage of participants]	94.0 43.7%	93.1 43.1%	96.3 44.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 8 Week
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF 8 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 8 Week
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments	The p-value for the comparison of the LDV/SOF+RBV 8 week group against the adjusted historical null rate (60%) was based on a 2-sided 1-sample binomial test.
	Method	Binomial test
	Comments

Statistical Analysis 3

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

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF+RBV 8 Week, LDV/SOF 12 Week
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Noninferiority would be demonstrated if the lower bound of the confidence interval (CI) for the difference between groups was greater than -12%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 97.5%; -8.3 to 1.8
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions.

Statistical Analysis 5

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 8 Week, LDV/SOF 12 Week
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Noninferiority would be demonstrated if the lower bound of the CI for the difference between groups was greater than -12%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	-2.3
	Confidence Interval	(2-Sided) 97.5%; -7.2 to 2.5
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions.

Statistical Analysis 6

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF 8 Week, LDV/SOF+RBV 8 Week
	Comments
	Type of Statistical Test	Non-Inferiority or Equivalence
	Comments	Noninferiority would be demonstrated if the lower bound of the CI for the difference between groups was greater than -12%.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in proportions
	Estimated Value	0.9
	Confidence Interval	(2-Sided) 95%; -3.9 to 5.7
	Parameter Dispersion	Type: Value:
	Estimation Comments	Difference in proportions between treatment groups and associated confidence interval (CI) were calculated based on stratum-adjusted Mantel-Haenszel proportions.

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 12 weeks

Outcome Measure Data

Analysis Population Description

Safety Analysis Set

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	216	216
Number [percentage of participants]	0 0%	0.9 0.4%	0.9 0.4%

3. Secondary Outcome

Title	Percentage of Participants With Sustained Virologic Response 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 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	216	216
SVR4	96.3 44.8%	94.9 43.9%	96.3 44.6%
SVR24	94.0 43.7%	93.1 43.1%	96.3 44.6%

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	214	216
Number [percentage of participants]	88.4 41.1%	91.1 42.2%	91.2 42.2%

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	216	213	216
Number [percentage of participants]	100.0 46.5%	99.1 45.9%	100.0 46.3%

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	213	214
Number [percentage of participants]	100.0 46.5%	100.0 46.3%	99.5 46.1%

7. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	212	212
Mean (Standard Deviation) [log10 IU/mL]	-5.06 (0.752)	-5.01 (0.675)	-4.99 (0.750)

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	212	216
Mean (Standard Deviation) [log10 IU/mL]	-5.12 (0.760)	-5.05 (0.682)	-5.05 (0.758)

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Participants in the Full Analysis Set with Available Data were analyzed.

Arm/Group Title	LDV/SOF 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	213	213
Mean (Standard Deviation) [log10 IU/mL]	-5.12 (0.760)	-5.05 (0.683)	-5.04 (0.761)

10. Secondary Outcome

Title	Percentage of Participants Experiencing 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 8 Week	LDV/SOF+RBV 8 Week	LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks	LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
Measure Participants	215	216	216
On-treatment virologic failure	0 0%	0 0%	0 0%
Virologic relapse	5.1 2.4%	4.2 1.9%	1.4 0.6%

Adverse Events

Time Frame	Up to 12 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set
Arm/Group Title	LDV/SOF 8 Week		LDV/SOF+RBV 8 Week		LDV/SOF 12 Week
Arm/Group Description	LDV 90 mg/SOF 400 mg FDC tablet once daily for 8 weeks		LDV 90 mg/SOF 400 mg FDC tablet once daily plus RBV tablets (1000 or 1200 mg daily based on weight) for 8 weeks		LDV 90 mg/SOF 400 mg FDC tablet once daily for 12 weeks
All Cause Mortality
	LDV/SOF 8 Week		LDV/SOF+RBV 8 Week		LDV/SOF 12 Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	LDV/SOF 8 Week		LDV/SOF+RBV 8 Week		LDV/SOF 12 Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/215 (1.9%)		1/216 (0.5%)		5/216 (2.3%)
Gastrointestinal disorders
Abdominal pain	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Colitis	1/215 (0.5%)		0/216 (0%)		0/216 (0%)
Lower gastrointestinal haemorrhage	1/215 (0.5%)		0/216 (0%)		0/216 (0%)
Hepatobiliary disorders
Bile duct stone	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Jaundice	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Immune system disorders
Anaphylactic reaction	1/215 (0.5%)		0/216 (0%)		0/216 (0%)
Injury, poisoning and procedural complications
Road traffic accident	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Skeletal injury	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Metabolism and nutrition disorders
Diabetes mellitus inadequate control	1/215 (0.5%)		0/216 (0%)		0/216 (0%)
Hypoglycaemia	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pituitary tumour	0/215 (0%)		1/216 (0.5%)		0/216 (0%)
Squamous cell carcinoma of lung	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Psychiatric disorders
Mental status changes	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Respiratory, thoracic and mediastinal disorders
Haemothorax 0	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Respiratory failure	0/215 (0%)		0/216 (0%)		1/216 (0.5%)
Vascular disorders
Hypertension	1/215 (0.5%)		0/216 (0%)		0/216 (0%)
Other (Not Including Serious) Adverse Events
	LDV/SOF 8 Week		LDV/SOF+RBV 8 Week		LDV/SOF 12 Week
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	146/215 (67.9%)		166/216 (76.9%)		150/216 (69.4%)
Blood and lymphatic system disorders
Anaemia	2/215 (0.9%)		17/216 (7.9%)		2/216 (0.9%)
Gastrointestinal disorders
Nausea	15/215 (7%)		39/216 (18.1%)		24/216 (11.1%)
Diarrhoea	15/215 (7%)		13/216 (6%)		9/216 (4.2%)
Constipation	9/215 (4.2%)		12/216 (5.6%)		8/216 (3.7%)
General disorders
Fatigue	45/215 (20.9%)		75/216 (34.7%)		49/216 (22.7%)
Irritability	3/215 (1.4%)		29/216 (13.4%)		10/216 (4.6%)
Musculoskeletal and connective tissue disorders
Arthralgia	9/215 (4.2%)		12/216 (5.6%)		16/216 (7.4%)
Muscle spasms	3/215 (1.4%)		12/216 (5.6%)		6/216 (2.8%)
Nervous system disorders
Headache	30/215 (14%)		54/216 (25%)		33/216 (15.3%)
Dizziness	6/215 (2.8%)		13/216 (6%)		9/216 (4.2%)
Psychiatric disorders
Insomnia	11/215 (5.1%)		26/216 (12%)		15/216 (6.9%)
Respiratory, thoracic and mediastinal disorders
Cough	3/215 (1.4%)		12/216 (5.6%)		7/216 (3.2%)
Dyspnoea	0/215 (0%)		11/216 (5.1%)		1/216 (0.5%)
Skin and subcutaneous tissue disorders
Rash	3/215 (1.4%)		20/216 (9.3%)		5/216 (2.3%)
Pruritus	2/215 (0.9%)		16/216 (7.4%)		5/216 (2.3%)

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