Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant

Phase 2CompletedNCT02010255

Gilead Sciences334 enrolled

Overview

This study will evaluate ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) plus ribavirin (RBV) in participants with advanced liver disease or posttransplant and chronic genotype 1 or 4 hepatitis C virus (HCV) infection. * Cohort A: decompensated cirrhosis (advanced liver disease), no prior liver transplant; * Cohort B: post-liver transplant, with or without cirrhosis; * Group assignment within cohorts is based on severity of liver impairment at screening (Child-Pugh-Turcotte (CPT) score for participants with cirrhosis; fibrosis; or presence of disease for fibrosing cholestatic hepatitis (FCH) groups) * Randomization is 1:1 within groups to 12 or 24 weeks of LDV/SOF+RBV treatment.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

334

Conditions

Chronic HCV Infection

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Able to provide written informed consent * Chronic genotype 1 and/or 4 HCV infection * Normal ECG * Negative serum pregnancy test for female subjects * Male subjects and female subjects of childbearing potential must agree to use contraception * Able to comply with the dosing instructions for study drug and able to complete the study schedule of assessments, including all required post treatment visits Exclusion Criteria: * Serious or active medical or psychiatric illness * HIV or hepatitis B viral (HBV) infection * Stomach disorder that could interfere with the absorption of the study drug * Treated with an anti-HCV medication in the last 30 days * Any prior exposure to an HCV nonstructural protein (NS)5a-specific inhibitor * Use of human granulocyte-macrophage colony-stimulating factor (GM-CSF), epoetin alfa or other therapeutic hematopoietic agents within 2 weeks of screening * History of clinically significant medical condition associated with other chronic liver disease * Active spontaneous bacterial peritonitis at screening * Females who are breastfeeding * Infection requiring systemic antibiotics * Participated in a clinical study with an investigational drug or biologic within the last 30 days * Active or history (last 6 months) of drug or alcohol abuse * History of organ transplant other than liver, kidney, or corneal.

Locations (34)

Royal Prince Alfred Hospital, University of Sydney

Camperdown, New South Wales, Australia

Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre

Heidelberg, Victoria, Australia

Medizinische Universitaet Innsbruck

Innsbruck, Austria

Medizinische Universitat Wien

Vienna, Austria

UCL St-Luc Brussels

Brussels, Belgium

Outcomes

Primary Outcomes

Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

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

Time frame: Posttreatment Week 12

Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

Time frame: Up to 24 weeks

Secondary Outcomes

Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)

SVR2 was defined as HCV RNA \< LLOQ at 2 weeks after stopping study treatment.

Time frame: Posttreatment Week 2

Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)

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

Time frame: Posttreatment Week 4

Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)

SVR8 was defined as HCV RNA \< LLOQ at 8 weeks after stopping study treatment.

Time frame: Posttreatment Week 8

Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)

SVR24 was defined as HCV RNA \< LLOQ at 24 weeks after stopping study treatment.

Time frame: Posttreatment Week 24

Percentage of Participants With Virologic Failure

Virologic failure was defined as: * On-treatment virologic failure: * Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA \< LLOQ on 2 consecutive measurements while on treatment), or * Rebound (confirmed \> 1 log10 IU/mL increase in HCV RNA from nadir while on treatment) * Virologic relapse: * Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA \< LLOQ at last on-treatment visit.

Time frame: Up to Posttreatment Week 24

Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12

pTVR was defined as HCV RNA \< LLOQ at Week 12 after transplant.

Time frame: Posttreatment Week 12

Percentage of Participants With HCV RNA < LLOQ at Week 1

Time frame: Week 1

Percentage of Participants With HCV RNA < LLOQ at Week 2

Time frame: Week 2

Percentage of Participants With HCV RNA < LLOQ at Week 4

Time frame: Week 4

Percentage of Participants With HCV RNA < LLOQ at Week 6

Time frame: Week 6

Percentage of Participants With HCV RNA < LLOQ at Week 8

Time frame: Week 8

Percentage of Participants With HCV RNA < LLOQ at Week 12

Time frame: Week 12

Percentage of Participants With HCV RNA < LLOQ at Week 16

Time frame: Week 16

Percentage of Participants With HCV RNA < LLOQ at Week 20

Time frame: Week 20

Percentage of Participants With HCV RNA < LLOQ at Week 24

Time frame: Week 24

HCV RNA Levels and Change From Baseline at Week 1

Time frame: Baseline; Week 1

HCV RNA Levels and Change From Baseline at Week 2

Time frame: Baseline; Week 2

HCV RNA Levels and Change From Baseline at Week 4

Time frame: Baseline; Week 4

HCV RNA Levels and Change From Baseline at Week 6

Time frame: Baseline; Week 6

HCV RNA Levels and Change From Baseline at Week 8

Time frame: Baseline; Week 8

HCV RNA Levels and Change From Baseline at Week 12

Time frame: Baseline; Week 12

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score

Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.

Time frame: Baseline to Posttreatment Week 4

Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score

CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15 (maximum score for entry into the study was 12); higher scores/increased scores indicate greater severity of disease. Groups are arranged by cohort, then by duration of treatment, then by CPT class at baseline.

Time frame: Baseline to Posttreatment Week 4