Trial Outcomes & Findings for Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting (NCT NCT02350569)

Last Updated: 2018-11-19

Results Overview

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

17 participants

Primary outcome timeframe

Posttreatment Week 12

Results posted on

2018-11-19

Participant Flow

Participants were enrolled at study sites in the United States. The first participant was screened on 22 May 2015. The last study visit occurred on 22 April 2016.

36 participants were screened. 17 unique participants were enrolled into the study (3 received the Day -1 dose and had their transplant cancelled; 2 of these patients were re-enrolled into the Main Study; the 3rd was rescreened but not transplanted).

Participant milestones

Participant milestones
Measure	LDV/SOF LDV/SOF for 1 Day: 3 participants were called for transplant, received one dose of ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg), but had their liver transplant cancelled. All 3 participants were rescreened and 2 were subsequently re-enrolled, transplanted, and continued into the Main Study. Main Study (LDV/SOF 4 Weeks): One dose of ledipasvir/sofosbuvir (Harvoni®; LDV/SOF) (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 hepatitis C virus (HCV) infection. Retreatment (LDV/SOF 12 Weeks): Participants who completed treatment in the Main Study and experienced virologic failure had the option to be retreated with LDV/SOF for 12 weeks.
Main Study (LDV/SOF 4 Weeks) STARTED	16
Main Study (LDV/SOF 4 Weeks) COMPLETED	16
Main Study (LDV/SOF 4 Weeks) NOT COMPLETED	0
Retreatment (LDV/SOF 12 Weeks) STARTED	1
Retreatment (LDV/SOF 12 Weeks) COMPLETED	1
Retreatment (LDV/SOF 12 Weeks) NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Safety and Efficacy of Ledipasvir/Sofosbuvir Fixed Dose Combination Administered in Patients Infected With Chronic Genotype 1 or 4 HCV for Use in the Peri-Operative Liver Transplantation Setting

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Age, Continuous	59 years STANDARD_DEVIATION 5.1 • n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	4 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
HCV Genotype Genotype 1a	11 Participants n=5 Participants
HCV Genotype Genotype 1b	5 Participants n=5 Participants
IL28b Status CC	5 Participants n=5 Participants
IL28b Status CT	9 Participants n=5 Participants
IL28b Status TT	2 Participants n=5 Participants
HCV RNA	5.6 log10 IU/mL STANDARD_DEVIATION 0.75 • n=5 Participants
HCV RNA Category < 800,000 IU/mL	10 Participants n=5 Participants
HCV RNA Category ≥ 800,000 IU/mL	6 Participants n=5 Participants
Prior HCV Treatment No	9 Participants n=5 Participants
Prior HCV Treatment Yes	7 Participants n=5 Participants

PRIMARY outcome

Timeframe: Posttreatment Week 12

Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug

SVR12 was defined as HCV RNA \< the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

Outcome measures

Outcome measures
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	87.5 percentage of participants Interval 61.7 to 98.4

PRIMARY outcome

Timeframe: Up to 4 weeks

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

Outcome measures

Outcome measures
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Percentage of Participants Who Prematurely Discontinued Study Drug Due to an Adverse Event	0 percentage of participants

SECONDARY outcome

Timeframe: Posttreatment Week 4

Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug

SVR4 was defined as HCV RNA \< LLOQ at 4 weeks after stopping study treatment.

Outcome measures

Outcome measures
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)	87.5 percentage of participants Interval 61.7 to 98.4

SECONDARY outcome

Timeframe: Up to Posttreatment Week 12

Population: Full Analysis Set: participants who were enrolled into the study, received a liver transplant while on study, and received at least 1 dose of study drug

Virologic failure was defined as: * End of treatment virologic failure: * Completed 28 days LDV/SOF treatment and had HCV RNA ≥ LLOQ at last measurement on treatment * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment HCV RNA measurement.

Outcome measures

Outcome measures
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Percentage of Participants With Virologic Failure	6.3 percentage of participants

SECONDARY outcome

Timeframe: Days 1, 3, 5, 7, 14, 21, and 28

Population: Participants in the Full Analysis Set with available data were analyzed.

Outcome measures

Outcome measures
Measure	Main Study (LDV/SOF 4 Weeks) n=16 Participants One dose of LDV/SOF (90/400 mg) immediately prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant in participants with chronic genotype 1 HCV infection
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 1	0 percentage of participants Interval 0.0 to 20.6
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 3	12.5 percentage of participants Interval 1.6 to 38.3
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 5	18.8 percentage of participants Interval 4.0 to 45.6
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 7	33.3 percentage of participants Interval 11.8 to 61.6
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 14	93.3 percentage of participants Interval 68.1 to 99.8
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 21	100.0 percentage of participants Interval 78.2 to 100.0
Percentage of Participants With HCV RNA < LLOQ While on Treatment at Days 1, 3, 5, 7, 14, 21, and 28 Day 28	100.0 percentage of participants Interval 78.2 to 100.0

Adverse Events

LDV/SOF for 1 Day

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Main Study (LDV/SOF 4 Weeks)

Serious events: 5 serious events

Other events: 14 other events

Deaths: 0 deaths

Retreatment (LDV/SOF 12 Weeks)

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	LDV/SOF for 1 Day n=3 participants at risk Adverse events reported in this group include participants who received LDV/SOF on Day -1, but did not receive a liver transplant. All 3 participants were rescreened, but only 2 were re-enrolled, transplanted, and received LDV/SOF for 4 weeks.	Main Study (LDV/SOF 4 Weeks) n=16 participants at risk Adverse events reported in this group include participants with chronic genotype 1 HCV infection who received one dose of LDV/SOF (90/400 mg) prior to receiving a liver transplant, followed by LDV/SOF (90/400 mg) once daily for 4 weeks following transplant.	Retreatment (LDV/SOF 12 Weeks) n=1 participants at risk Adverse events reported in this group include 1 participant who completed treatment and experienced virologic failure in the Main Study and was retreated with an additional 12 weeks of LDV/SOF.
Hepatobiliary disorders Bile duct stenosis	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Hepatobiliary disorders Cholangitis	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Infections and infestations Incision site cellulitis	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Injury, poisoning and procedural complications Biliary anastomosis complication	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Investigations Blood creatinine increased	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Investigations Hepatic artery flow decreased	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Metabolism and nutrition disorders Decreased appetite	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Metabolism and nutrition disorders Hyperkalaemia	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug
Renal and urinary disorders Acute kidney injury	0.00% 0/3 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	6.2% 1/16 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug	0.00% 0/1 • LDV/SOF for 1 Day: After pre-dose to minimum of 30 days or restart of LDV/SOF; Main Study: After pretransplant dose up to 4 weeks plus 30 days; Retreatment: After pretransplant dose up to 12 weeks plus 30 days Safety Analysis Set: participants who were enrolled into the study and received at least 1 dose of study drug

Other adverse events

Additional Information

Clinical Trial Disclosures

Gilead Sciences

Email: [email protected]

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