Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Participants With Chronic Genotype 1 HCV Infection

• Sponsor: Gilead Sciences (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02021656
• Collaborator: (none)
• Enrollment: 384
• Locations: 45
• Arm: 1
• Actual Duration (Months): 45.6
• Patients Per Site: 8.5
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The primary objectives of this study are to evaluate the efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in treatment-naive and treatment-experienced participants with chronic genotype 1 hepatitis C virus (HCV) infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic HCV Infection	Drug: LDV/SOF	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 384 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination in Treatment-Naïve and Treatment-Experienced Subjects With Chronic Genotype 1 HCV Infection
• Actual Study Start Date: Dec 10, 2013
• Actual Primary Completion Date: Jul 8, 2017
• Actual Study Completion Date: Sep 29, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: LDV/SOF Treatment-experienced and treatment-naive participants will receive LDV/SOF for 12 weeks.	Drug: LDV/SOF; 90/400 mg FDC tablet administered orally once daily without regard to food; 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 in Korea and Taiwan and < 15 IU/mL in China) 12 weeks following the last dose of study drug.

2. Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event [Up to 12 weeks]

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 Experiencing Viral Breakthrough [Up to 12 weeks]

   Viral breakthrough were defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR).

3. Percentage of Participants Experiencing Viral Relapse [Week 12 to Posttreatment Week 24]

   Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.

4. HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only [Baseline; Week 12]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Key Inclusion Criteria:

• Willing and able to provide written informed consent

• HCV RNA ≥ 10^4 IU/mL at screening

• HCV treatment-naive, as defined as no prior exposure to any interferon (IFN) or other approved or experimental HCV-specific direct-acting antiviral agent; OR HCV treatment-experienced with medical records that include sufficient detail of prior IFN-based treatment to allow for categorization of prior response as either intolerant, non-responder, or experienced viral breakthrough or relapse.

• Genotype 1 HCV at screening

• HCV infection documented by anti-HCV antibody test, genotyping test, or liver biopsy

Key Exclusion Criteria:

• Pregnant or nursing female

• Chronic liver disease of a non-HCV etiology

• Current or prior history of any clinically-significant illness (other than HCV)

• Infection with hepatitis B virus (HBV) or human immunodeficiency virus (HIV)

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1		Beijing		China	100015
2		Beijing		China	100034
3		Beijing		China	100044
4		Beijing		China	100050
5		Beijing		China	100069
6		Chongqing		China	400010
7		Guangdong		China	510515
8		Guangxi		China	530021
9		Hubei		China	430030
10		Hunan		China	410011
11		Jiangxi		China	210029
12		Jiangxi		China	330006
13		Jilin		China	130021
14		Shandong		China	250021
15		Shanghai		China	200025
16		Shanghai		China	200083
17		Shijiazhuang		China	050051
18		Sichuan		China	610041
19		Ansan-si	Gyeonggi-do	Korea, Republic of	425-707
20		Bucheon	Gyeonggi-do	Korea, Republic of	420-767
21		Incheon	Gyeonggi-do	Korea, Republic of	405-760
22		Seongnam-si	Gyeonggi-do	Korea, Republic of	467-707
23		Busan		Korea, Republic of	602-715
24		Busan		Korea, Republic of	602-739
25		Busan		Korea, Republic of	614-735
26		Daegu		Korea, Republic of	700-721
27		Seoul		Korea, Republic of	110-744
28		Seoul		Korea, Republic of	120-752
29		Seoul		Korea, Republic of	135-720
30		Seoul		Korea, Republic of	137-701
31		Seoul		Korea, Republic of	138-736
32		Seoul		Korea, Republic of	152-703
33		Seoul		Korea, Republic of	735-710
34		Changhua City		Taiwan	50006
35		Kaohsiung City		Taiwan	80708
36		Kaohsiung City		Taiwan	82445
37		Kaohsiung City		Taiwan	83301
38		Keelung		Taiwan	20401
39		Taichung City		Taiwan	40447
40		Tainan City		Taiwan	70457
41		Tainan city		Taiwan	73657
42		Taipei City		Taiwan	10048
43		Taipei City		Taiwan	10449
44		Taipei City		Taiwan	11217
45		Taoyuan		Taiwan	33305

Sponsors and Collaborators

• Gilead Sciences

Investigators

• Study Director: Gilead Study Director, Gilead Sciences

Study Documents (Full-Text)

• Study Protocol: Original - May 28, 2013
• Study Protocol: Amendment 2 - Aug 1, 2014
• Study Protocol: Amendment 3 - Feb 12, 2016
• Statistical Analysis Plan - Jul 28, 2017

More Information

Publications

None provided.

• Responsible Party: Gilead Sciences
• ClinicalTrials.gov Identifier: NCT02021656
• Other Study ID Numbers: GS-US-337-0131
• First Posted: Dec 27, 2013
• Last Update Posted: Mar 5, 2020
• Last Verified: Jan 1, 2019

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Infections; Communicable Diseases; Hepatitis C; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir

Study Results

Participant Flow

Recruitment Details	Participants were enrolled at study sites in Mainland China (referred to as China throughout this results record), Korea, and Taiwan. The first participant was screened on 10 December 2013. The last study visit occurred on 29 September 2017.
Pre-assignment Detail	416 participants were screened.

Arm/Group Title	LDV/SOF (Overall)
Arm/Group Description	Ledipasvir/sofosbuvir (LDV/SOF) (90/400 mg) fixed-dose combination (FDC) tablet once daily administered without regard to food for 12 weeks in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan
Period Title: Overall Study
STARTED	384
COMPLETED	378
NOT COMPLETED	6

Baseline Characteristics

Arm/Group Title	LDV/SOF
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily without regard to food for 12 weeks in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan
Overall Participants	384
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]	51 (13.0)
Sex: Female, Male (Count of Participants)
Female	202 52.6%
Male	182 47.4%
Race/Ethnicity, Customized (Count of Participants)
Chinese	207 53.9%
Korean	93 24.2%
Taiwanese	83 21.6%
Other (Taiwanese- Chinese)	1 0.3%
Race/Ethnicity, Customized (Count of Participants)
Not Hispanic or Latino	384 100%
Region of Enrollment (Count of Participants)
South Korea	93 24.2%
China	206 53.6%
Taiwan	85 22.1%
IL28B (Count of Participants)
CC	286 74.5%
CT	95 24.7%
TT	3 0.8%

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 in Korea and Taiwan and < 15 IU/mL in China) 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 enrolled and received at least 1 dose of study drug, and have chronic genotype 1 HCV infection.

Arm/Group Title	LDV/SOF: China	LDV/SOF: Overall
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan without regard to food for 12 weeks
Measure Participants	206	384
Number (95% Confidence Interval) [Percentage of participants]	100.0 26%	99.2 NaN

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	LDV/SOF: China
	Comments	A sample size of 100 Chinese participants in the treatment naive group provided at least 90% power to detect a 17% improvement in SVR12 rate from the historical control rate of 57% using 2-sided exact one-sample binomial test at significant level of 0.05.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Binomial Exact Test
	Comments

2. Primary Outcome

Title	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	LDV/SOF: China	LDV/SOF: Overall
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan without regard to food for 12 weeks
Measure Participants	206	384
Number [percentage of participants]	0 0%	0.5 NaN

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: China	LDF/SOF: Overall
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks.	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in Korea and Taiwan without regard to food for 12 weeks.
Measure Participants	206	384
SVR4	100.0 26%	99.2 NaN
SVR24	100.0 26%	99.0 NaN

4. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Breakthrough
Description	Viral breakthrough were defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) during treatment, but did not achieve a sustained virologic response (SVR).
Time Frame	Up to 12 weeks

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF: China	LDF/SOF: Overall
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks.	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan without regard to food for 12 weeks.
Measure Participants	206	384
Number [percentage of participants]	0 0%	0 NaN

5. Secondary Outcome

Title	Percentage of Participants Experiencing Viral Relapse
Description	Viral relapse is defined as having achieved undetectable HCV RNA levels (HCV RNA < LLOQ) within 4 weeks of end of treatment, but did not achieve an SVR.
Time Frame	Week 12 to Posttreatment Week 24

Outcome Measure Data

Analysis Population Description

Full Analysis Set

Arm/Group Title	LDV/SOF: China	LDF/SOF: Overall
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks.	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan without regard to food for 12 weeks.
Measure Participants	206	384
Number [percentage of participants]	0 0%	0.5 NaN

6. Secondary Outcome

Title	HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only
Time Frame	Baseline; Week 12

Outcome Measure Data

Analysis Population Description

Only Chinese participants in the Full Analysis set were analyzed.

Arm/Group Title	LDV/SOF: China
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily in treatment-experienced and treatment-naive participants in China without regard to food for 12 weeks
Measure Participants	206
Baseline	6.31 (0.633)
Change at Week 12	-5.16 (0.633)

Adverse Events

Time Frame	Up to 12 weeks plus 30 days
Adverse Event Reporting Description	Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Arm/Group Title	LDV/SOF (Overall)
Arm/Group Description	LDV/SOF (90/400 mg) FDC tablet administered once daily without regard to food for 12 weeks in treatment-experienced and treatment-naive participants in China, Korea, and Taiwan
All Cause Mortality
	LDV/SOF (Overall)
	Affected / at Risk (%)	# Events
Total	0/384 (0%)
Serious Adverse Events
	LDV/SOF (Overall)
	Affected / at Risk (%)	# Events
Total	7/384 (1.8%)
Infections and infestations
Erysipelas	1/384 (0.3%)
Injury, poisoning and procedural complications
Bone contusion	1/384 (0.3%)
Epicondylitis	1/384 (0.3%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Small cell lung cancer	1/384 (0.3%)
Reproductive system and breast disorders
Adenomyosis	1/384 (0.3%)
Endometriosis	1/384 (0.3%)
Respiratory, thoracic and mediastinal disorders
Asthma	1/384 (0.3%)
Skin and subcutaneous tissue disorders
Dermatitis contact	1/384 (0.3%)
Other (Not Including Serious) Adverse Events
	LDV/SOF (Overall)
	Affected / at Risk (%)	# Events
Total	105/384 (27.3%)
Infections and infestations
Upper respiratory tract infection	42/384 (10.9%)
Viral upper respiratory tract infection	44/384 (11.5%)
Nervous system disorders
Headache	27/384 (7%)

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