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

Phase 2CompletedNCT01938430

Gilead Sciences339 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

339

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 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 or kidney

Locations (30)

Unnamed facility

Phoenix, Arizona, United States

Unnamed facility

San Diego, California, United States

Unnamed facility

San Francisco, California, United States

Unnamed facility

Aurora, Colorado, United States

Unnamed facility

Washington D.C., District of Columbia, United States

Unnamed facility

Jacksonville, Florida, United States

Unnamed facility

Miami, Florida, United States

Unnamed facility

Chicago, Illinois, United States

Unnamed facility

Indianapolis, Indiana, United States

Unnamed facility

Kansas City, Kansas, United States

...and 20 more locations

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: Posttransplant 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 and Change From Baseline at Week 1

Time frame: Baseline; Week 1

HCV RNA and Change From Baseline at Week 2

Time frame: Baseline; Week 2

HCV RNA and Change From Baseline at Week 4

Time frame: Baseline; Week 4

HCV RNA and Change From Baseline at Week 6

Time frame: Baseline; Week 6

HCV RNA and Change From Baseline at Week 8

Time frame: Baseline; Week 8

HCV RNA 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