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

Tracking Information

• First Submitted Date: November 10, 2012
• First Posted Date: November 15, 2012
• Results First Submitted Date: November 7, 2014
• Results First Posted Date: November 17, 2014
• Last Update Posted Date: November 16, 2018
• Study Start Date: October 2012
• Actual Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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.

Current Secondary Outcome Measures (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 (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 Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Efficacy of LDV/SOF Fixed-Dose Combination (FDC) ± Ribavirin in HCV Genotype 1 Subjects
• 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
• 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C Virus

Intervention

• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 7, 2012): 100
• Original Estimated Enrollment (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

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, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01726517
• Other Study ID Numbers: GS-US-337-0118
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

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
• Supporting Materials: 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

• Current Responsible Party: Gilead Sciences
• Original Responsible Party: Same as current
• Current Study Sponsor: Gilead Sciences
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Rob Hyland; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: November 2014