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

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Chronic HCV Infection

Treatments: Drug: LDV/SOF; Drug: RBV

Study type: Interventional

Funder types: Industry

Identifiers

NCT01938430

GS-US-337-0123

Details and patient eligibility

About

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.

Enrollment: 339 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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339 participants in 14 patient groups

Cohort A, Group 1 (12 wk): CPT Class B (7-9)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort A, Group 1 (24 wk): CPT Class B (7-9)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort A, Group 2 (12 wk): CPT Class C (10-12)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort A, Group 2 (24 wk): CPT Class C (10-12)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 3 (12 wk): F0-F3 Fibrosis

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with Fibrosis Stage F0-F3.

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 3 (24 wk): F0-F3 Fibrosis

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with Fibrosis Stage F0-F3

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 4 (12 wk): CPT Class A (5-6)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with CPT Class A (CPT score 5-6)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 4 (24 wk): CPT Class A (5-6)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with CPT Class A (CPT score 5-6)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 5 (12 wk): CPT Class B (7-9)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class B (CPT score 7-9)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 5 (24 wk): CPT Class B (7-9)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class B (CPT score 7-9)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 6 (12 wk): CPT Class C (10-12)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 12 weeks in participants with CPT Class C (CPT score 10-12)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 6 (24 wk): CPT Class C (10-12)

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (starting at 600 mg, then adjusted ± based on tolerability \[weight-based maximum: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg\]) for 24 weeks in participants with CPT Class C (CPT score 10-12)

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 7 (12 wk): FCH

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 12 weeks in participants with FCH

Treatment:

Drug: RBV

Drug: LDV/SOF

Cohort B, Group 7 (24 wk): FCH

Experimental group

Description:

LDV/SOF (90/400 mg) plus RBV (weight-based: \< 75 kg = 1000 mg, ≥ 75 kg = 1200 mg) for 24 weeks in participants with FCH

Treatment:

Drug: RBV

Drug: LDV/SOF