Phase 2
N=339
Ledipasvir/Sofosbuvir Fixed-Dose Combination + Ribavirin in Subjects With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant
Chronic HCV Infection
Bottom Line
View on ClinicalTrials.gov: NCT01938430 ↗Enrolled (actual)
339
Serious AEs
22.9%
Results posted
Apr 2016
Primary outcome: Primary: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) — 86.7; 88.9; 86.4; 87.0 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
- Jan 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) |
86.7; 88.9; 86.4; 87.0; 96.4; 98.2 | — |
| PRIMARY Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event |
0.0; 6.9; 4.3; 7.7; 0.0; 3.6 | — |
| SECONDARY Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2) |
96.7; 92.6; 95.5; 95.8; 100.0; 98.2 | — |
| SECONDARY Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4) |
90.0; 88.9; 90.9; 95.7; 96.4; 98.2 | — |
| SECONDARY Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8) |
86.7; 88.9; 86.4; 95.7; 96.4; 98.2 | — |
| SECONDARY Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24) |
86.7; 88.9; 85.7; 87.0; 96.4; 98.2 | — |
| SECONDARY Percentage of Participants With Virologic Failure |
10.0; 3.7; 4.5; 8.7; 3.6; 0.0 | — |
| SECONDARY Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12 |
85.7 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 1 |
6.7; 6.9; 13.0; 3.8; 16.4; 12.5 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 2 |
36.7; 41.4; 39.1; 38.5; 49.1; 41.8 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 4 |
83.3; 82.8; 100.0; 84.6; 87.3; 90.9 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 6 |
100.0; 100.0; 100.0; 96.2; 96.4; 100.0 | — |
| SECONDARY Percentage of Participants With HCV RNA < LLOQ at Week 8 |
100.0; 96.6; 100.0; 92.0; 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 and Change From Baseline at Week 1 |
2.26; 2.49; 2.11; 2.46; 2.33; 2.42 | — |
| SECONDARY HCV RNA and Change From Baseline at Week 2 |
1.60; 1.67; 1.49; 1.82; 1.64; 1.59 | — |
| SECONDARY HCV RNA and Change From Baseline at Week 4 |
1.20; 1.21; 1.15; 1.23; 1.24; 1.16 | — |
| SECONDARY HCV RNA and Change From Baseline at Week 6 |
1.15; 1.15; 1.15; 1.15; 1.15; 1.15 | — |
| SECONDARY HCV RNA and Change From Baseline at Week 8 |
1.15; 1.15; 1.15; 1.16; 1.15; 1.15 | — |
| SECONDARY HCV RNA 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 |
60.7; 68.0; 61.9; 80.0; 30.4; 52.0 | — |
| SECONDARY Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score |
0.0; 63.3; 50.0; 89.5; 72.2; 18.2 | — |
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 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
Data sourced from ClinicalTrials.gov (NCT01938430). 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.