Phase 2 N=334 Randomized Treatment

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

Chronic HCV Infection

Bottom Line

View on ClinicalTrials.gov: NCT02010255 ↗

Enrolled (actual)

334

Serious AEs

21.9%

Results posted

Jun 2016

Primary outcome: Primary: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) — 84.6; 96.0; 81.0; 76.0 percentage of participants

Study Design & Population

Study type: Interventional
Phase: Phase 2
Interventions: LDV/SOF (Drug); RBV (Drug)
Age: Adult, Older Adult · 18+ yrs
Sex: All
Sponsor: Gilead Sciences
Primary completion: May 2015

Outcome Measures

Outcome	Result	p-value
PRIMARY Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	84.6; 96.0; 81.0; 76.0; 94.2; 100.0	—
PRIMARY Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event	3.6; 3.6; 0.0; 7.7; 1.9; 0.0	—
SECONDARY Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)	96.2; 100.0; 91.3; 80.0; 98.1; 100.0	—
SECONDARY Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)	88.5; 100.0; 90.9; 80.0; 94.2; 100.0	—
SECONDARY Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)	84.6; 96.2; 81.8; 80.0; 94.2; 100.0	—
SECONDARY Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)	84.0; 96.0; 80.0; 76.0; 94.2; 100.0	—
SECONDARY Percentage of Participants With Virologic Failure	15.4; 4.0; 9.5; 4.0; 1.9; 0.0	—
SECONDARY Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12	100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 1	3.8; 3.7; 12.0; 3.8; 9.6; 6.1	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 2	26.9; 37.0; 40.0; 38.5; 48.1; 44.9	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 4	76.9; 81.5; 80.0; 84.6; 84.6; 91.8	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 6	100.0; 100.0; 91.7; 100.0; 98.1; 100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 8	100.0; 100.0; 100.0; 96.0; 100.0; 100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 12	100.0; 100.0; 100.0; 100.0; 100.0; 100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 16	100.0; 100.0; 100.0; 100.0; 100.0; 100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 20	100.0; 100.0; 100.0; 100.0; 100.0; 100.0	—
SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 24	100.0; 100.0; 100.0; 100.0; 100.0; 100.0	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 1	2.44; 2.47; 2.32; 2.50; 2.38; 2.38	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 2	1.76; 1.70; 1.71; 1.72; 1.62; 1.49	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 4	1.26; 1.20; 1.23; 1.18; 1.23; 1.18	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 6	1.15; 1.15; 1.17; 1.15; 1.15; 1.15	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 8	1.15; 1.15; 1.15; 1.15; 1.15; 1.15	—
SECONDARY HCV RNA Levels and Change From Baseline at Week 12	1.15; 1.15; 1.15; 1.15; 1.15; 1.15	—
SECONDARY Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score	70.8; 77.3; 81.0; 70.0; 28.1; 62.5	—
SECONDARY Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score	64.3; 87.0; 82.4; 73.7; 28.6; 23.5	—

Summary

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.

Eligibility Criteria

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.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02010255). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.