Trial Outcomes & Findings for Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination in Participants With Chronic Genotype 1 HCV Infection (NCT NCT02021656)

NCT ID: NCT02021656

Last Updated: 2020-03-05

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 384 participants
• Primary outcome timeframe: Posttreatment Week 12
• Results posted on: 2020-03-05

Participant Flow

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.

416 participants were screened.

Participant milestones

Measure	LDV/SOF (Overall) 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
Overall Study STARTED	384
Overall Study COMPLETED	378
Overall Study NOT COMPLETED	6

Reasons for withdrawal

Measure	LDV/SOF (Overall) 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
Overall Study Adverse Event	1
Overall Study Lack of Efficacy	2
Overall Study Lost to Follow-up	1
Overall Study Withdrew Consent	2

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	LDV/SOF n=384 Participants 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
Age, Continuous	51 Years STANDARD_DEVIATION 13.0 • n=5 Participants
Sex: Female, Male Female	202 Participants n=5 Participants
Sex: Female, Male Male	182 Participants n=5 Participants
Race/Ethnicity, Customized Race Subcategory · Chinese	207 Participants n=5 Participants
Race/Ethnicity, Customized Race Subcategory · Korean	93 Participants n=5 Participants
Race/Ethnicity, Customized Race Subcategory · Taiwanese	83 Participants n=5 Participants
Race/Ethnicity, Customized Race Subcategory · Other (Taiwanese- Chinese)	1 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	384 Participants n=5 Participants
Region of Enrollment South Korea	93 Participants n=5 Participants
Region of Enrollment China	206 Participants n=5 Participants
Region of Enrollment Taiwan	85 Participants n=5 Participants
IL28B CC	286 Participants n=5 Participants
IL28B CT	95 Participants n=5 Participants
IL28B TT	3 Participants n=5 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12

Population: Full analysis set: participants who were enrolled and received at least 1 dose of study drug, and have chronic genotype 1 HCV infection.

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.

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall n=384 Participants 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
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)	100.0 Percentage of participants Interval 98.2 to 100.0	99.2 Percentage of participants Interval 97.7 to 99.8

PRIMARY outcome

Timeframe: Up to 12 weeks

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

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall n=384 Participants 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
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event	0 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: Posttreatment Weeks 4 and 24

Population: Full Analysis Set

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

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall n=384 Participants 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
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) SVR4	100.0 percentage of participants Interval 98.2 to 100.0	99.2 percentage of participants Interval 97.7 to 99.8
Percentage of Participants With Sustained Virologic Response at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) SVR24	100.0 percentage of participants Interval 98.2 to 100.0	99.0 percentage of participants Interval 97.4 to 99.7

SECONDARY outcome

Timeframe: Up to 12 weeks

Population: Full Analysis Set

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).

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall n=384 Participants 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
Percentage of Participants Experiencing Viral Breakthrough	0 percentage of participants	0 percentage of participants

SECONDARY outcome

Timeframe: Week 12 to Posttreatment Week 24

Population: Full Analysis Set

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.

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall n=384 Participants 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
Percentage of Participants Experiencing Viral Relapse	0 percentage of participants	0.5 percentage of participants

SECONDARY outcome

Timeframe: Baseline; Week 12

Population: Only Chinese participants in the Full Analysis set were analyzed.

Outcome measures

Measure	LDV/SOF: China n=206 Participants 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: Overall 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
HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only Baseline	6.31 log10 IU/mL Standard Deviation 0.633	—
HCV RNA and Change From Baseline in HCV RNA Through Week 12 for China Only Change at Week 12	-5.16 log10 IU/mL Standard Deviation 0.633	—

Adverse Events

LDV/SOF (Overall)

Serious events: 7 serious events

Other events: 105 other events

Deaths: 0 deaths

Serious adverse events

Measure	LDV/SOF (Overall) n=384 participants at risk 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
Infections and infestations Erysipelas	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Injury, poisoning and procedural complications Bone contusion	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Injury, poisoning and procedural complications Epicondylitis	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Small cell lung cancer	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Reproductive system and breast disorders Adenomyosis	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Reproductive system and breast disorders Endometriosis	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Respiratory, thoracic and mediastinal disorders Asthma	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Skin and subcutaneous tissue disorders Dermatitis contact	0.26% 1/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study

Other adverse events

Measure	LDV/SOF (Overall) n=384 participants at risk 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
Infections and infestations Upper respiratory tract infection	10.9% 42/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Infections and infestations Viral upper respiratory tract infection	11.5% 44/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study
Nervous system disorders Headache	7.0% 27/384 • Up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled and received at least 1 dose of study

Additional Information

Gilead Clinical Study Information Center

Gilead Sciences

Phone: 1-833-445-3230 (GILEAD-0)

Email: GileadClinicalTrials@gilead.com

Results disclosure agreements

• Principal investigator is a sponsor employee 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
• Publication restrictions are in place

Restriction type: OTHER