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

• ClinicalTrials.gov Identifier: NCT01726517
• Recruitment Status: Completed
• First Posted: November 15, 2012
• Results First Posted: November 17, 2014
• Last Update Posted: November 16, 2018
• Sponsor: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Study Description

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

• 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

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

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

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• 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

Locations

United States, Texas

San Antonio, Texas, United States, 78215

Sponsors and Collaborators

Gilead Sciences

Investigators

• Study Director: Rob Hyland; Gilead Sciences

More Information

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
• Other Study ID Numbers: GS-US-337-0118
• First Posted: November 15, 2012
• Results First Posted: November 17, 2014
• Last Update Posted: November 16, 2018
• Last Verified: November 2014

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Qualified external researchers may request IPD for this study after study completion. For more information, please visit our website at http://www.gilead.com/research/disclosure-and-transparency.
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP)
• Time Frame: 18 months after study completion
• Access Criteria: A secured external environment with username, password, and RSA code.
• URL: http://www.gilead.com/research/disclosure-and-transparency

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 C, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Ledipasvir, sofosbuvir drug combination; Antiviral Agents; Anti-Infective Agents