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

NCT02010255 | Completed Phase 2 Results DMC

• 2 other identifiers: GS-US-337-01242013-002802-30
• Study Type: interventional
• Target: 334
• Locations: 11 countries
• Sites: 32

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

Outcome Measures

Primary Outcomes (2)

• 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

• Percentage of Participants Who Discontinued Study Drug Due to an Adverse Event

  Up to 24 weeks

Secondary Outcomes (23)

• Percentage of Participants With SVR 2 Weeks After Discontinuation of Therapy (SVR2)

  Posttreatment Week 2

• Percentage of Participants With SVR 4 Weeks After Discontinuation of Therapy (SVR4)

  Posttreatment Week 4

• Percentage of Participants With SVR 8 Weeks After Discontinuation of Therapy (SVR8)

  Posttreatment Week 8

• Percentage of Participants With SVR 24 Weeks After Discontinuation of Therapy (SVR24)

  Posttreatment Week 24

• Percentage of Participants With Virologic Failure

  Up to Posttreatment Week 24

Study Arms (14)

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

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

EXPERIMENTAL

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)

Drug: LDV/SOF; Drug: RBV

Cohort B, Group 7 (12 wk): FCH

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: RBV

Cohort B, Group 7 (24 wk): FCH

EXPERIMENTAL

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

Drug: LDV/SOF; Drug: RBV

Interventions

LDV/SOF DRUG

LDV/SOF FDC tablet administered orally once daily

Also known as: Harvoni®, GS-5885/GS-7977

Cohort A, Group 1 (12 wk): CPT Class B (7-9); Cohort A, Group 1 (24 wk): CPT Class B (7-9); Cohort A, Group 2 (12 wk): CPT Class C (10-12); Cohort A, Group 2 (24 wk): CPT Class C (10-12); Cohort B, Group 3 (12 wk): F0-F3 Fibrosis; Cohort B, Group 3 (24 wk): F0-F3 Fibrosis; Cohort B, Group 4 (12 wk): CPT Class A (5-6); Cohort B, Group 4 (24 wk): CPT Class A (5-6); Cohort B, Group 5 (12 wk): CPT Class B (7-9); Cohort B, Group 5 (24 wk): CPT Class B (7-9); Cohort B, Group 6 (12 wk): CPT Class C (10-12); Cohort B, Group 6 (24 wk): CPT Class C (10-12); Cohort B, Group 7 (12 wk): FCH; Cohort B, Group 7 (24 wk): FCH

RBV DRUG

RBV tablets administered orally in a divided daily dose

Cohort A, Group 1 (12 wk): CPT Class B (7-9); Cohort A, Group 1 (24 wk): CPT Class B (7-9); Cohort A, Group 2 (12 wk): CPT Class C (10-12); Cohort A, Group 2 (24 wk): CPT Class C (10-12); Cohort B, Group 3 (12 wk): F0-F3 Fibrosis; Cohort B, Group 3 (24 wk): F0-F3 Fibrosis; Cohort B, Group 4 (12 wk): CPT Class A (5-6); Cohort B, Group 4 (24 wk): CPT Class A (5-6); Cohort B, Group 5 (12 wk): CPT Class B (7-9); Cohort B, Group 5 (24 wk): CPT Class B (7-9); Cohort B, Group 6 (12 wk): CPT Class C (10-12); Cohort B, Group 6 (24 wk): CPT Class C (10-12); Cohort B, Group 7 (12 wk): FCH; Cohort B, Group 7 (24 wk): FCH

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (34)

Royal Prince Alfred Hospital, University of Sydney

Camperdown, New South Wales, 2050, Australia

Location

Austin Repatriation Hospital (Melbourne) // Victorian Transplant Centre

Heidelberg, Victoria, 3084, Australia

Location

Medizinische Universitaet Innsbruck

Innsbruck, A-6020, Austria

Location

Medizinische Universitat Wien

Vienna, 1090, Austria

Location

UCL St-Luc Brussels

Brussels, 1200, Belgium

Location

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

Location

Division of Gastroenterology, University of Alberta, Edmonton

Edmonton, Alberta, T6G 2C2, Canada

Location

University of British Columbia and Vancouver General Hospital

Vancouver, British Columbia, V5Z 3P1, Canada

Location

London Health Sciences Centre-University Hospital

London, Ontario, N6A 5A5, Canada

Location

University Health Network // Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

Hopital St. Luc

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University Health Centre \\ Royal Victoria Hospital

Montreal, Quebec, H3A 1A1, Canada

Location

Hospital Beaujon

Clichy, 92118, France

Location

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

Créteil, 94010, France

Location

Hopital Saint-Eloi

Montpellier, 34295, France

Location

Hopital Paul Brousse

Villejuif, 94804, France

Location

Universitätsklinikum RWTH Aachen

Aachen, 52074, Germany

Location

Universitätsklinikum Essen - klinikum für Gastroenterolgie und Hepatologie

Essen, 45122, Germany

Location

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

Frankfurt, 60590, Germany

Location

Medical School of Hannover

Hanover, 30625, Germany

Location

IRCCS Cà Grande Ospedale Maggiore Policlinico

Milan, 20122, Italy

Location

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

Torino, 10126, Italy

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Erasmus MC in Rotterdam

Rotterdam, 3015 CE, Netherlands

Location

Auckland City Hospital

Auckland, 1023, New Zealand

Location

Hospital General Universitari Vall d' Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic i Provincial

Barcelona, 8036, Spain

Location

Puerta de Hierro, Madrid

Madrid, 28220, Spain

Location

Hospital Universitario y Politecnico La Fe de Valencia

Valencia, 46009, Spain

Location

University of Berne

Bern, 3010, Switzerland

Location

University Hospital Zurich

Zurich, CH-8091, Switzerland

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, B15 2TH, United Kingdom

Location

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

Edinburgh, EH3 9YW, United Kingdom

Location

Kings College Hospital, Institute of Liver Studies

London, SE5 9RS, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 26907736 DERIVED

MeSH Terms

Interventions

ledipasvir, sofosbuvir drug combination

Limitations and Caveats

There were no limitations affecting the analysis or results.

Results Point of Contact

• Title: Clinical Trial Disclosures
• Organization: Gilead Sciences

ClinicalTrialDisclosures@gilead.com

Study Officials

• Shampa De-Oertel, PhD

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2013
• First Posted: December 12, 2013
• Study Start: January 1, 2014
• Primary Completion: May 1, 2015
• Study Completion: August 1, 2015
• Last Updated: November 19, 2018
• Results First Posted: June 20, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.

Locations

IT (2); GB (3); DE (4); FR (4); BE (2); CA (6); NL (2); NZ (1); ES (4); AU (2); CH (2)