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Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection

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ClinicalTrials.gov Identifier: NCT02073656
Recruitment Status : Completed
First Posted : February 27, 2014
Results First Posted : October 21, 2016
Last Update Posted : November 16, 2018
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE February 25, 2014
First Posted Date  ICMJE February 27, 2014
Results First Submitted Date  ICMJE August 30, 2016
Results First Posted Date  ICMJE October 21, 2016
Last Update Posted Date November 16, 2018
Study Start Date  ICMJE February 2014
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 30, 2016)
  • Percentage of Participants With Sustained Virologic Response (SVR) 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) at 12 weeks after stopping study treatment.
  • Percentage of Participants Who Permanently Discontinued Any Study Drug Due to an Adverse Event [ Time Frame: Up to 12 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: February 25, 2014)
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ) 12 weeks following the last dose of study drug.
  • Incidence of adverse events leading to permanent discontinuation of study drug(s) [ Time Frame: Baseline to Week 12 ]
Change History Complete list of historical versions of study NCT02073656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 30, 2016)
  • Percentage of Participants With SVR at 4 and 24 Weeks After Discontinuation of Therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR 24 were defined as HCV RNA < LLOQ at 4 and 24 weeks after stopping study treatment, respectively.
  • Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 6, 8, 10, and 12 [ Time Frame: Weeks 1, 2, 4, 6, 8, 10, and 12 ]
  • Change From Baseline in HCV RNA at Weeks 1, 2, 4, 6, and 8 [ Time Frame: Baseline; Weeks 1, 2, 4, 6, and 8 ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]
    Virologic failure was defined as:
    • On-treatment virologic failure:
      • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
      • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
      • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
    • Virologic relapse:
      • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
  • Percentage of Participants That Maintain HIV-1 RNA < 50 Copies/mL While on HCV Treatment [ Time Frame: Weeks 4, 8, and 12 ]
  • Change From Baseline in Serum Creatinine at the End of Treatment (Week 12) and at Posttreatment Weeks 12 and 24 [ Time Frame: Baseline; Week 12, Posttreatment Weeks 12 and 24 ]
  • For Participants in the Retreatment Substudy, Percentage of Participants With SVR at 4, 12, and 24 Weeks After Discontinuation of Therapy (SVR4, SVR12, and SVR24) [ Time Frame: Posttreatment Weeks 4, 12, and 24 of Retreatment Substudy ]
    SVR4, SVR12, and SVR 24 were defined as HCV RNA < LLOQ at 4, 12, and 24 weeks after stopping study treatment, respectively.
  • For Participants in the Retreatment Substudy, Percentage of Participants With HCV RNA < LLOQ at Retreatment Weeks 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Weeks 2, 4, 8, 12, 16, 20, and 24 of the Retreatment Substudy ]
  • For Participants in the Retreatment Substudy, Change From Baseline in HCV RNA at Retreatment Weeks 2, 4, and 8 [ Time Frame: Baseline; Weeks 2, 4, and 8 of Retreatment Substudy ]
  • For Participants in the Retreatment Substudy, Percentage of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 of Retreatment Substudy ]
    Virologic failure was defined as:
    • On-treatment virologic failure:
      • Breakthrough (confirmed HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while on treatment), or
      • Rebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), or
      • Non-response (HCV RNA persistently ≥ LLOQ through 8 weeks of treatment)
    • Virologic relapse:
      • Confirmed HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at last on-treatment visit.
Original Secondary Outcome Measures  ICMJE
 (submitted: February 25, 2014)
  • Proportion of participants with sustained virologic response at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
    SVR4 and SVR24 is defined as HCV RNA < LLOQ at 4 and 24 weeks following the last dose of study drug, respectively.
  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 12 weeks ]
  • Change in HCV RNA from baseline [ Time Frame: Baseline to posttreatment Week 24 ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to posttreatment Week 24 ]
    Virologic failure is defined as virologic breakthrough (participant achieved undetectable HCV RNA levels during treatment but subsequently had detectable HCV RNA while continuing treatment), nonresponse (HCV RNA ≥ LLOQ through 12 weeks of treatment), or relapse (participant achieved undetectable HCV RNA levels during treatment maintained undetectable HCV RNA for the duration of treatment or achieved undetectable HCV RNA within 4 weeks of the end of treatment but did not achieve SVR at 4, 12, or 24 weeks posttreatment).
  • For retreatment group only: Proportion of participants with sustained virologic response at 4, 12 and 24 weeks after discontinuation of therapy (SVR4, SVR12, and SVR24) [ Time Frame: Posttreatment Weeks 4, 12, and 24 ]
  • Proportion of participants that maintain HIV-1 RNA < 50 copies/mL while on treatment [ Time Frame: Baseline to Week 12 ]
  • Change from baseline of serum creatinine at end of treatment, posttreatment weeks 12 and 24 [ Time Frame: Week 12 and posttreatment weeks 12 and 24 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 HCV and HIV-1 Co-infection
Official Title  ICMJE A Phase 3, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination for 12 Weeks in Subjects With Chronic Genotype 1 or 4 Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV)-1 Co-infection
Brief Summary

This study will evaluate the antiviral efficacy, safety, and tolerability of ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) administered for 12 weeks in hepatitis C virus (HCV) treatment-naive and treatment-experienced (including treatment intolerant) participants with chronic genotype 1 or 4 HCV infection who are co-infected with HIV-1.

Participants who experience confirmed post-treatment virologic failure (relapse) at or before Posttreatment Week 24 may be eligible to be enrolled in the Retreatment Substudy to receive LDV/SOF plus ribavirin (RBV) for 24 weeks.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Hepatitis C Virus
  • HIV
Intervention  ICMJE
  • Drug: LDV/SOF
    90/400 mg FDC tablet administered orally once daily
    Other Names:
    • Harvoni®
    • GS-5885/GS-7977
  • Drug: 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  ICMJE
  • Experimental: LDV/SOF 12 Weeks
    LDV/SOF for 12 weeks
    Intervention: Drug: LDV/SOF
  • Experimental: Retreatment Substudy
    LDV/SOF plus RBV for 24 weeks
    Interventions:
    • Drug: LDV/SOF
    • Drug: RBV
Publications *

*   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: July 1, 2015)
335
Original Estimated Enrollment  ICMJE
 (submitted: February 25, 2014)
300
Actual Study Completion Date  ICMJE December 2015
Actual Primary Completion Date November 2014   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • HCV RNA ≥ 10,000 IU/mL at screening
  • HCV genotype 1 or 4
  • HIV-1 infection
  • Cirrhosis determination, a fibroscan or liver biopsy may be required
  • Screening laboratory values within defined thresholds
  • Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male

Exclusion Criteria:

  • Clinically-significant illness (other than HCV or HIV) or any other major medical disorder that may interfere with subject treatment, assessment, or compliance with the protocol
  • Current or prior history of clinical hepatic decompensation, hepatocellular carcinoma (HCC), or other malignancy (with the exception of certain resolved skin cancers)
  • Hepatitis B virus (HBV) infection
  • Pregnant or nursing female
  • Chronic use of systemically administered immunosuppressive agents
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   New Zealand,   Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02073656
Other Study ID Numbers  ICMJE GS-US-337-0115
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
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
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Jenny Yang, PharmD Gilead Sciences
PRS Account Gilead Sciences
Verification Date August 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP