Clinical trial NCT01938430: Ledipasvir/Sofosbuvir Fixed-Dose Combination + Ribavirin in Subjects With Chronic HCV With Advanced Liver Disease or Post-Liver Transplant
Official title: A Phase 2, Multicenter, Open-Label Study to Investigate the Safety and Efficacy of Sofosbuvir/Ledipasvir Fixed-Dose Combination + Ribavirin Administered in Subjects Infected With Chronic HCV Who Have Advanced Liver Disease or Are Post-Liver Transplant
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic HCV Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-09-10
Enrollment: 339
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event
timeFrame: Up to 24 weeks
Secondary outcomes:
measure: Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)
timeFrame: Posttreatment Week 2
measure: Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)
timeFrame: Posttreatment Week 8
measure: Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)
timeFrame: Posttreatment Week 24
measure: Percentage of Participants With Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12
timeFrame: Posttransplant Week 12
measure: Percentage of Participants With HCV RNA < LLOQ at Week 1
timeFrame: Week 1
measure: Percentage of Participants With HCV RNA < LLOQ at Week 2
timeFrame: Week 2
measure: Percentage of Participants With HCV RNA < LLOQ at Week 4
timeFrame: Week 4
measure: Percentage of Participants With HCV RNA < LLOQ at Week 6
timeFrame: Week 6
measure: Percentage of Participants With HCV RNA < LLOQ at Week 8
timeFrame: Week 8
measure: Percentage of Participants With HCV RNA < LLOQ at Week 12
timeFrame: Week 12
measure: Percentage of Participants With HCV RNA < LLOQ at Week 16
timeFrame: Week 16
measure: Percentage of Participants With HCV RNA < LLOQ at Week 20
timeFrame: Week 20
measure: Percentage of Participants With HCV RNA < LLOQ at Week 24
timeFrame: Week 24
measure: HCV RNA and Change From Baseline at Week 1
timeFrame: Baseline; Week 1
measure: HCV RNA and Change From Baseline at Week 2
timeFrame: Baseline; Week 2
measure: HCV RNA and Change From Baseline at Week 4
timeFrame: Baseline; Week 4
measure: HCV RNA and Change From Baseline at Week 6
timeFrame: Baseline; Week 6
measure: HCV RNA and Change From Baseline at Week 8
timeFrame: Baseline; Week 8
measure: HCV RNA and Change From Baseline at Week 12
timeFrame: Baseline; Week 12
measure: Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score
timeFrame: Baseline to Posttreatment Week 4
measure: Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score
timeFrame: Baseline to Posttreatment Week 4
Other outcomes:
Locations:
city: Phoenix
country: United States
state: Arizona
city: San Diego
country: United States
state: California
city: San Francisco
country: United States
state: California
city: Aurora
country: United States
state: Colorado
city: Washington
country: United States
state: District of Columbia
city: Jacksonville
country: United States
state: Florida
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Indianapolis
country: United States
state: Indiana
city: Kansas City
country: United States
state: Kansas
city: Lutherville
country: United States
state: Maryland
city: Boston
country: United States
state: Massachusetts
city: Ann Arbor
country: United States
state: Michigan
city: Detroit
country: United States
state: Michigan
city: Minneapolis
country: United States
state: Minnesota
city: Rochester
country: United States
state: Minnesota
city: Saint Louis
country: United States
state: Missouri
city: New York
country: United States
state: New York
city: New York
country: United States
state: New York
city: Chapel Hill
country: United States
state: North Carolina
city: Durham
country: United States
state: North Carolina
city: Cleveland
country: United States
state: Ohio
city: Portland
country: United States
state: Oregon
city: Philadelphia
country: United States
state: Pennsylvania
city: Pittsburgh
country: United States
state: Pennsylvania
city: Dallas
country: United States
state: Texas
city: Murray
country: United States
state: Utah
city: Richmond
country: United States
state: Virginia
city: Seattle
country: United States
state: Washington
city: Seattle
country: United States
state: Washington
Study officials:
affiliation: Gilead Sciences
name: Shampa De-Oertel, PhD
role: STUDY_DIRECTOR
References:
citation: Welzel TM, Reddy KR, Flamm SL, Denning J, Lin M, Hyland R, Pang PS, McHutchison JG, Charlton M, Everson GT, Zeuzem S, Afdhal N. On-treatment HCV RNA in patients with varying degrees of fibrosis and cirrhosis in the SOLAR-1 trial. Antivir Ther. 2016;21(6):541-546. doi: 10.3851/IMP3037. Epub 2016 Feb 18.
citation: Charlton M, Everson GT, Flamm SL, Kumar P, Landis C, Brown RS Jr, Fried MW, Terrault NA, O'Leary JG, Vargas HE, Kuo A, Schiff E, Sulkowski MS, Gilroy R, Watt KD, Brown K, Kwo P, Pungpapong S, Korenblat KM, Muir AJ, Teperman L, Fontana RJ, Denning J, Arterburn S, Dvory-Sobol H, Brandt-Sarif T, Pang PS, McHutchison JG, Reddy KR, Afdhal N; SOLAR-1 Investigators. Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease. Gastroenterology. 2015 Sep;149(3):649-59. doi: 10.1053/j.gastro.2015.05.010. Epub 2015 May 15.