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

Chronic HCV Infection Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02010255
• Other study ID #: GS-US-337-0124
• Secondary ID: 2013-002802-30
• Status: Completed
• Phase: Phase 2
• Start date: January 2014
• Est. completion date: August 2015

Study information

• Verified date: May 2016
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 334
• Est. completion date: August 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic HCV Infection
• Liver Diseases

Intervention

Drug:
• LDV/SOF
LDV/SOF FDC tablet administered orally once daily
• RBV
RBV tablets administered orally in a divided daily dose

Locations

Country	Name	City	State
Australia	Royal Prince Alfred Hospital, University of Sydney	Camperdown	New South Wales
Australia	Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre	Heidelberg	Victoria
Austria	Medizinische Universitaet Innsbruck	Innsbruck
Austria	Medizinische Universitat Wien	Wien
Belgium	UCL St-Luc Brussels	Brussels
Belgium	Universitair Ziekenhuis Gent	Gent
Canada	Division of Gastroenterology, University of Alberta, Edmonton	Edmonton	Alberta
Canada	London Health Sciences Centre-University Hospital	London	Ontario
Canada	Hopital St. Luc	Montreal	Quebec
Canada	McGill University Health Centre \\ Royal Victoria Hospital	Montreal	Quebec
Canada	University Health Network // Toronto General Hospital	Toronto	Ontario
Canada	University of British Columbia and Vancouver General Hospital	Vancouver	British Columbia
France	Hospital Beaujon	Clichy Cedex
France	Hospital Mondor \\ Service d'Hépatologie et de Gastroentérologie,	Créteil
France	Hopital Saint-Eloi	Montpellier
France	Hopital Paul Brousse	Villejuif Cedex
Germany	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	Hannover
Italy	IRCCS Cà Grande Ospedale Maggiore Policlinico	Milano
Italy	Azienda Ospedaliera San Giovanni, Battista di Torino \\ Professor of Gastroenterology-San Giovanni Battista Hospital-University of Torino	Torino
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Erasmus MC in Rotterdam	Rotterdam
New Zealand	Auckland City Hospital	Auckland
Spain	Hospital Clinic i Provincial	Barcelona
Spain	Hospital General Universitari Vall d' Hebron	Barcelona
Spain	Puerta de Hierro, Madrid	Madrid
Spain	Hospital Universitario y Politecnico La Fe de Valencia	Valencia
Switzerland	University of Berne	Bern
Switzerland	University Hospital Zurich	Zurich
United Kingdom	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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Primary	Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event		Up to 24 weeks
Secondary	Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)	SVR2 was defined as HCV RNA < LLOQ at 2 weeks after stopping study treatment.	Posttreatment Week 2
Secondary	Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.	Posttreatment Week 4
Secondary	Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)	SVR8 was defined as HCV RNA < LLOQ at 8 weeks after stopping study treatment.	Posttreatment Week 8
Secondary	Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)	SVR24 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.	Posttreatment Week 24
Secondary	Percentage of Participants With Virologic Failure	Virologic failure was defined as: On-treatment virologic failure: Breakthrough (confirmed HCV RNA = LLOQ after having previously had HCV RNA < LLOQ on 2 consecutive measurements while on treatment), or; Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment); Virologic relapse: Confirmed HCV RNA = LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.	Up to Posttreatment Week 24
Secondary	Percentage of Participants With Posttransplant Virologic Response (pTVR) at Posttransplant Week 12	pTVR was defined as HCV RNA < LLOQ at Week 12 after transplant.	Posttreatment Week 12
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 1		Week 1
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 2		Week 2
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 4		Week 4
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 6		Week 6
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 8		Week 8
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 12		Week 12
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 16		Week 16
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 20		Week 20
Secondary	Percentage of Participants With HCV RNA < LLOQ at Week 24		Week 24
Secondary	HCV RNA Levels and Change From Baseline at Week 1		Baseline; Week 1
Secondary	HCV RNA Levels and Change From Baseline at Week 2		Baseline; Week 2
Secondary	HCV RNA Levels and Change From Baseline at Week 4		Baseline; Week 4
Secondary	HCV RNA Levels and Change From Baseline at Week 6		Baseline; Week 6
Secondary	HCV RNA Levels and Change From Baseline at Week 8		Baseline; Week 8
Secondary	HCV RNA Levels and Change From Baseline at Week 12		Baseline; Week 12
Secondary	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in MELD Score	Model for End-Stage Liver Disease (MELD) scores are used to assess prognosis and suitability for liver transplantation. Scores can range from 6 to 40; higher scores/increased scores indicate greater severity of disease.	Baseline to Posttreatment Week 4
Secondary	Percentage of Participants With a Decrease, No Change, or Increase Between Baseline and Posttreatment Week 4 in CPT Score	CPT scores grade the severity of cirrhosis and are used to determine the need for liver transplantation. Scores can range from 5 to 15 (maximum score for entry into the study was 12); higher scores/increased scores indicate greater severity of disease. Groups are arranged by cohort, then by duration of treatment, then by CPT class at baseline.	Baseline to Posttreatment Week 4