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

Tracking Information
First Submitted Date ICMJE	November 10, 2012
First Posted Date ICMJE	November 15, 2012
Results First Submitted Date	November 7, 2014
Results First Posted Date	November 17, 2014
Last Update Posted Date	November 17, 2014
Study Start Date ICMJE	October 2012
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: November 7, 2014)	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.; 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.
Original Primary Outcome Measures ICMJE; (submitted: November 10, 2012)	Sustained virologic response after discontinuation of therapy [ Time Frame: 12 weeks after discontinuation of therapy ]Sustained virologic response (SVR) 12 weeks after the end of treatment (SVR12 defined as HCV RNA < lower limit of quantification [LLOQ] 12 weeks after last dose of study drug).; Safety and tolerability of combination treatment with sofosbuvir (SOF)/GS-5885 fixed-dose combination (FDC) +/- RBV as measured by review of the accumulated safety data. [ Time Frame: Safety and tolerability on treatment and 30 days post last dose. ]Frequency and severity of adverse events.
Change History	Complete list of historical versions of study NCT01726517 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: November 7, 2014)	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.; 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.
Original Secondary Outcome Measures ICMJE; (submitted: November 10, 2012)	Sustained virologic response after discontinuation of therapy. [ Time Frame: 2,4,8, and 24 weeks after discontinuation of therapy ]Sustained virologic response (SVR) at 2,4,8, and 24 weeks after discontinuation of therapy (SVR 2, SVR4, SVR 8, and SVR24 defined as HCV RNA < lower limit of quantification [LLOQ] after last dose of study drug).; Viral resistance to sofosbuvir and GS-5885 combination therapy during and after treatment. [ Time Frame: 12 and 24 weeks ]To evaluate the emergence of viral resistance to sofosbuvir and GS-5885 during treatment and after treatment discontinuation; Characterization of viral dynamics during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ]To characterize viral dynamics during treatment and after treatment discontinuation.; Characterization of steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation. [ Time Frame: 12 and 24 weeks ]To characterize steady state pharmacokinetics of sofosbuvir and GS-5885 during treatment and after treatment discontinuation.
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
Official Title ICMJE	A Phase 2, Randomized, Open-Label Study of Sofosbuvir/GS-5885 Fixed-Dose Combination ± Ribavirin in Subjects With Chronic Genotype 1 HCV Infection
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.
Detailed Description	Not Provided
Study Type ICMJE	Interventional
Study Phase	Phase 2
Study Design ICMJE	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Chronic Hepatitis C Virus
Intervention ICMJE	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)
Study Arms	Experimental: LDV/SOF 8 Weeks (TN) Treatment-naive (TN) participants will be randomized to receive LDV/SOF for 8 weeks. Intervention: Drug: LDV/SOF; Experimental: LDV/SOF+RBV 8 Weeks (TN) Treatment-naive participants will be randomized to receive LDV/SOF plus RBV for 8 weeks. Interventions: Drug: LDV/SOF Drug: RBV; Experimental: LDV/SOF 12 Weeks (TN) Treatment-naive participants will be randomized to receive LDV/SOF for 12 weeks. Intervention: Drug: LDV/SOF; 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. Intervention: Drug: LDV/SOF; 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. Interventions: Drug: LDV/SOF Drug: RBV
Publications *	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.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: December 7, 2012)	100
Original Estimated Enrollment ICMJE; (submitted: November 10, 2012)	60
Actual Study Completion Date	January 2014
Actual Primary Completion Date	July 2013 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	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
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years and older (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT01726517
Other Study ID Numbers ICMJE	GS-US-337-0118
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Gilead Sciences
Study Sponsor ICMJE	Gilead Sciences
Collaborators ICMJE	Not Provided
Investigators ICMJE	Study Director: Rob Hyland Gilead Sciences
PRS Account	Gilead Sciences
Verification Date	November 2014
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP