Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects

Study Description

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Brief Summary:

This study is to evaluate the safety, tolerability, and antiviral efficacy of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) with or without ribavirin (RBV), administered for 8 or 12 weeks of treatment in participants with chronic genotype 1 hepatitis C virus (HCV) infection who are treatment-naive, and for 12 weeks in participants who had previously received a regimen containing a protease inhibitor for the treatment of HCV.

Condition or disease	Intervention/treatment	Phase
Chronic Hepatitis C Virus	Drug: LDV/SOF; Drug: RBV	Phase 2

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	100 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection
Study Start Date :	October 2012
Actual Primary Completion Date :	July 2013
Actual Study Completion Date :	January 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: LDV/SOF 8 Weeks (TN); Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Name: Harvoni®
Experimental: LDV/SOF+RBV 8 Weeks (TN); Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Name: Harvoni® Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)
Experimental: LDV/SOF 12 Weeks (TN); Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Name: Harvoni®
Experimental: LDV/SOF 12 Weeks (TE); Treatment-experienced (TE) participants (had virologic failure following prior therapy with a protease-inhibitor [PI]+pegylated interferon [PEG]+RBV regimen) will be randomized to receive LDV/SOF for 12 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Name: Harvoni®
Experimental: LDV/SOF+RBV 12 Weeks (TE); Treatment-experienced participants (had virologic failure following prior therapy with a PI+PEG+RBV regimen) will be randomized to receive LDV/SOF plus RBV for 12 weeks.	Drug: LDV/SOF; LDV 90 mg/SOF 400 mg FDC tablet administered orally once daily; Other Name: Harvoni® Drug: RBV; RBV tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75 kg = 1000 mg and ≥ 75 kg = 1200 mg)

Outcome Measures

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Primary Outcome Measures :

1. Percentage of Participants With Sustained Virologic Response (SVR) at 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
   SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 25 IU/mL) 12 weeks after stopping study treatment.
2. Incidence of Adverse Events Leading to Permanent Discontinuation of Study Drug(s) [ Time Frame: Baseline to Week 12 ]
   The number of participants experiencing an adverse event leading to permanent discontinuation of study drug(s) was summarized.

Secondary Outcome Measures :

1. Percentage of Participants With SVR at 2, 4, 8, and 24 Weeks After Discontinuation of Therapy (SVR2, SVR4, SVR8, and SVR24) [ Time Frame: Posttreatment Weeks 2, 4, 8, and 24 ]
   SVR2, SVR4, SVR8, and SVR24 was defined as HCV RNA < LLOQ at 2, 4, 8, and 24 weeks following the last dose of study drug, respectively.
2. Percentage of Participants Experiencing Viral Breakthrough or Viral Relapse [ Time Frame: Baseline to Posttreatment Week 24 ]
   • Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.
   • Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

• Age ≥ 18 years, with chronic genotype 1 HCV infection
• HCV RNA equal to or greater than 10,000 IU/mL at screening
• Cirrhosis determination; a liver biopsy may be required
• Screening laboratory values within defined thresholds
• Use of two effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers)
• Chronic use of systemic immunosuppressive agents
• History of clinically significant illness or any other medical disorder that may interfere with subject treatment, assessment or compliance with the protocol

Contacts and Locations

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Locations

United States, Texas
San Antonio, Texas, United States, 78215

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:	Rob Hyland	Gilead Sciences

More Information

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Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Lawitz E, Poordad FF, Pang PS, Hyland RH, Ding X, Mo H, Symonds WT, McHutchison JG, Membreno FE. Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin in treatment-naive and previously treated patients with genotype 1 hepatitis C virus infection (LONESTAR): an open-label, randomised, phase 2 trial. Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub 2013 Nov 5. Erratum in: Lancet. 2014 Mar 8;383(9920):870.

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01726517 History of Changes
Other Study ID Numbers:	GS-US-337-0118
First Posted:	November 15, 2012
Results First Posted:	November 17, 2014
Last Update Posted:	November 17, 2014
Last Verified:	November 2014

Keywords provided by Gilead Sciences:

HCV genotype 1 (GT-1); HCV; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; GS-7977; GS-5885	Ribavirin; Open Label; Sofosbuvir; Treatment-Naïve; Protease Inhibitors; PI

Additional relevant MeSH terms:

Hepatitis C; Hepatitis, Chronic; Hepatitis C, Chronic; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis; Liver Diseases	Digestive System Diseases; Ribavirin; Sofosbuvir; Protease Inhibitors; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Antiviral Agents; Anti-Infective Agents; Enzyme Inhibitors