Clinical trial NCT02010255: Ledipasvir/Sofosbuvir Fixed-Dose Combination Plus Ribavirin in Participants 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: 2013-12-12
Enrollment: 334
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 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.

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: Posttreatment 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 Levels and Change From Baseline at Week 1
timeFrame: Baseline; Week 1
measure: HCV RNA Levels and Change From Baseline at Week 2
timeFrame: Baseline; Week 2
measure: HCV RNA Levels and Change From Baseline at Week 4
timeFrame: Baseline; Week 4
measure: HCV RNA Levels and Change From Baseline at Week 6
timeFrame: Baseline; Week 6
measure: HCV RNA Levels and Change From Baseline at Week 8
timeFrame: Baseline; Week 8
measure: HCV RNA Levels 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: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital, University of Sydney
state: New South Wales
city: Heidelberg
country: Australia
facility: Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre
state: Victoria
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Wien
country: Austria
facility: Medizinische Universitat Wien
city: Brussels
country: Belgium
facility: UCL St-Luc Brussels
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Edmonton
country: Canada
facility: Division of Gastroenterology, University of Alberta, Edmonton
state: Alberta
city: Vancouver
country: Canada
facility: University of British Columbia and Vancouver General Hospital
state: British Columbia
city: London
country: Canada
facility: London Health Sciences Centre-University Hospital
state: Ontario
city: Toronto
country: Canada
facility: University Health Network // Toronto General Hospital
state: Ontario
city: Montreal
country: Canada
facility: Hopital St. Luc
state: Quebec
city: Montreal
country: Canada
facility: McGill University Health Centre \\ Royal Victoria Hospital
state: Quebec
city: Clichy Cedex
country: France
facility: Hospital Beaujon
city: Créteil
country: France
facility: Hospital Mondor \\ Service d'Hépatologie et de Gastroentérologie,
city: Montpellier
country: France
facility: Hopital Saint-Eloi
city: Villejuif Cedex
country: France
facility: Hopital Paul Brousse
city: Aachen
country: Germany
facility: Universitätsklinikum RWTH Aachen
city: Essen
country: Germany
facility: Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie
city: Frankfurt
country: Germany
facility: University Hospital Johann Wolfgang Goethe University, Department of Internal Medicine I
city: Hannover
country: Germany
facility: Medical School of Hannover
city: Milano
country: Italy
facility: IRCCS Cà Grande Ospedale Maggiore Policlinico
city: Torino
country: Italy
facility: Azienda Ospedaliera San Giovanni, Battista di Torino \\ Professor of Gastroenterology-San Giovanni Battista Hospital-University of Torino
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Rotterdam
country: Netherlands
facility: Erasmus MC in Rotterdam
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Barcelona
country: Spain
facility: Hospital General Universitari Vall d' Hebron
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial
city: Madrid
country: Spain
facility: Puerta de Hierro, Madrid
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe de Valencia
city: Bern
country: Switzerland
facility: University of Berne
city: Zurich
country: Switzerland
facility: University Hospital Zurich
city: Birmingham
country: United Kingdom
facility: University Hospitals Birmingham NHS Foundation Trust
city: Edinburgh
country: United Kingdom
facility: Royal Infirmary of Edinburgh \\ Scottish Liver Transplant Unit-Edinburgh
city: London
country: United Kingdom
facility: Kings College Hospital, Institute of Liver Studies
Study officials:
affiliation: Gilead Sciences
name: Shampa De-Oertel, PhD
role: STUDY_DIRECTOR
References:
citation: Manns M, Samuel D, Gane EJ, Mutimer D, McCaughan G, Buti M, Prieto M, Calleja JL, Peck-Radosavljevic M, Mullhaupt B, Agarwal K, Angus P, Yoshida EM, Colombo M, Rizzetto M, Dvory-Sobol H, Denning J, Arterburn S, Pang PS, Brainard D, McHutchison JG, Dufour JF, Van Vlierberghe H, van Hoek B, Forns X; SOLAR-2 investigators. Ledipasvir and sofosbuvir plus ribavirin in patients with genotype 1 or 4 hepatitis C virus infection and advanced liver disease: a multicentre, open-label, randomised, phase 2 trial. Lancet Infect Dis. 2016 Jun;16(6):685-697. doi: 10.1016/S1473-3099(16)00052-9. Epub 2016 Feb 18.