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

NCT ID: NCT02010255

Last Updated: 2018-11-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 334 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-01-31
• Study Completion Date: 2015-08-31

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.

Conditions

Chronic HCV Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

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

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)

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

Cohort B, Group 7 (12 wk): FCH

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

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

Cohort B, Group 7 (24 wk): FCH

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

Group Type: EXPERIMENTAL

LDV/SOF

Intervention Type: DRUG

LDV/SOF FDC tablet administered orally once daily

RBV

Intervention Type: DRUG

RBV tablets administered orally in a divided daily dose

Interventions

LDV/SOF

LDV/SOF FDC tablet administered orally once daily

Intervention Type: DRUG

RBV

RBV tablets administered orally in a divided daily dose

Intervention Type: DRUG

Other Intervention Names

Harvoni®; GS-5885/GS-7977

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Shampa De-Oertel, PhD

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

Royal Prince Alfred Hospital, University of Sydney

Camperdown, New South Wales, Australia

Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre

Heidelberg, Victoria, Australia

Medizinische Universitaet Innsbruck

Innsbruck, , Austria

Medizinische Universitat Wien

Vienna, , Austria

UCL St-Luc Brussels

Brussels, , Belgium

Universitair Ziekenhuis Gent

Ghent, , Belgium

Division of Gastroenterology, University of Alberta, Edmonton

Edmonton, Alberta, Canada

University of British Columbia and Vancouver General Hospital

Vancouver, British Columbia, Canada

London Health Sciences Centre-University Hospital

London, Ontario, Canada

University Health Network // Toronto General Hospital

Toronto, Ontario, Canada

Hopital St. Luc

Montreal, Quebec, Canada

McGill University Health Centre \\ Royal Victoria Hospital

Montreal, Quebec, Canada

Hospital Beaujon

Clichy, , France

Hospital Mondor \\ Service d'Hépatologie et de Gastroentérologie,

Créteil, , France

Hopital Saint-Eloi

Montpellier, , France

Hopital Paul Brousse

Villejuif, , France

Universitätsklinikum RWTH Aachen

Aachen, , Germany

Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie

Essen, , Germany

University Hospital Johann Wolfgang Goethe University, Department of Internal Medicine I

Frankfurt, , Germany

Medical School of Hannover

Hanover, , Germany

IRCCS Cà Grande Ospedale Maggiore Policlinico

Milan, , Italy

Azienda Ospedaliera San Giovanni, Battista di Torino \\ Professor of Gastroenterology-San Giovanni Battista Hospital-University of Torino

Torino, , Italy

Leids Universitair Medisch Centrum

Leiden, , Netherlands

Erasmus MC in Rotterdam

Rotterdam, , Netherlands

Auckland City Hospital

Auckland, , New Zealand

Hospital General Universitari Vall d' Hebron

Barcelona, , Spain

Hospital Clinic i Provincial

Barcelona, , Spain

Puerta de Hierro, Madrid

Madrid, , Spain

Hospital Universitario y Politecnico La Fe de Valencia

Valencia, , Spain

University of Berne

Bern, , Switzerland

University Hospital Zurich

Zurich, , Switzerland

University Hospitals Birmingham NHS Foundation Trust

Birmingham, , United Kingdom

Royal Infirmary of Edinburgh \\ Scottish Liver Transplant Unit-Edinburgh

Edinburgh, , United Kingdom

Kings College Hospital, Institute of Liver Studies

London, , United Kingdom

Countries

Australia; Austria; Belgium; Canada; France; Germany; Italy; Netherlands; New Zealand; Spain; Switzerland; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 26907736 (View on PubMed)

Other Identifiers

2013-002802-30

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GS-US-337-0124

Identifier Type: -

Identifier Source: org_study_id