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Efficacy and Safety of Ledipasvir/Sofosbuvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders

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ClinicalTrials.gov Identifier: NCT02120300
Recruitment Status : Completed
First Posted : April 22, 2014
Results First Posted : December 6, 2016
Last Update Posted : December 6, 2016
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE April 18, 2014
First Posted Date  ICMJE April 22, 2014
Results First Submitted Date  ICMJE August 16, 2016
Results First Posted Date  ICMJE December 6, 2016
Last Update Posted Date December 6, 2016
Study Start Date  ICMJE April 2014
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 13, 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, 15 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 24 weeks ]
Original Primary Outcome Measures  ICMJE
 (submitted: April 18, 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 up to Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2016)
  • Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.
  • Percentage of Participants With HCV RNA < LLOQ at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Weeks 1, 2, 4, 8, 12, 16, 20, and 24 ]
  • Change From Baseline in HCV RNA at Weeks 1, 2, 4, 8, 12, 16, 20, and 24 [ Time Frame: Baseline; Weeks 1, 2, 4, 8, 12, 16, 20, and 24 ]
  • 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 at Weeks 4, 8, 12, 16, 20, and 24 (HIV-1/HCV Co-infected Participants Only) [ Time Frame: Weeks 4, 8, 12, 16, 20, and 24 ]
  • Change From Baseline in Serum Creatinine at the End of Treatment and at Posttreatment Week 12 (HIV-1/HCV Co-infected Participants Only) [ Time Frame: Baseline; Weeks 12, 24, and Posttreatment Week 12 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: April 18, 2014)
  • Proportion of participants with sustained virologic response (SVR) at 4 weeks after discontinuation of therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 is defined as HCV RNA < LLOQ at 4 weeks following the last dose of study drug.
  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to 24 weeks ]
  • HCV RNA change from baseline [ Time Frame: Baseline up to Week 24 ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to posttreatment Week 12 ]
    Virologic failure is defined as:
    • Breakthrough: HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ, while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Rebound: > 1 log10IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values (note: second confirmation value can be posttreatment), or last available on-treatment measurement with no subsequent follow up values, OR
    • Nonresponse: HCV RNA persistently ≥ LLOQ through 8 weeks of treatment, OR
    • Relapse: 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
  • For HIV-1/HCV co-infected participants, the proportion of subjects that maintain HIV-1 RNA < 50 copies/mL while on HCV treatment [ Time Frame: Up to 24 weeks ]
  • For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at the end of treatment [ Time Frame: Baseline up to Week 24 ]
  • For HIV-1/HCV co-infected participants, change from baseline of serum creatinine at posttreatment Week 12 [ Time Frame: Baseline to posttreatment Week 12 ]
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 and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
Official Title  ICMJE A Phase 2b, Multicenter, Open-Label Study to Investigate the Efficacy and Safety of Sofosbuvir/Ledipasvir Fixed-Dose Combination and Sofosbuvir + Ribavirin for Subjects With Chronic Hepatitis C Virus (HCV) and Inherited Bleeding Disorders
Brief Summary The primary objectives of this study are to evaluate the antiviral efficacy, safety, and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) fixed-dose combination (FDC) in participants with genotypes 1 and 4 hepatitis C virus (HCV) infection and sofosbuvir (SOF) plus ribavirin (RBV) in participants with genotypes 2 and 3 HCV infection. Participants with an inherited bleeding disorder and chronic HCV infection (either monoinfected or HIV-1/HCV coinfected) will be enrolled.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Chronic HCV Infection
Intervention  ICMJE
  • Drug: LDV/SOF
    90/400 mg FDC tablet administered orally
    Other Names:
    • Harvoni®
    • GS-5885/GS-7977
  • Drug: SOF
    400 mg tablet administered orally once daily
    Other Names:
    • Sovaldi®
    • GS-7977
    • PSI-7977
  • Drug: RBV
    Ribavirin (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 GT 1 or 4
    Participants with chronic genotypes (GT) 1 or 4 HCV infection will receive LDV/SOF for 12 or 24 weeks. Treatment-experienced cirrhotic participants with genotype 1 HCV infection will receive LDV/SOF for 24 weeks.
    Intervention: Drug: LDV/SOF
  • Experimental: SOF+RBV 12 wks GT 2
    Participants with chronic genotype 2 HCV infection will receive SOF+RBV for 12 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
  • Experimental: SOF+RBV 24 wks GT 3
    Participants with chronic genotype 3 HCV infection will receive SOF+RBV for 24 weeks.
    Interventions:
    • Drug: SOF
    • Drug: RBV
Publications * Walsh C, Workowski K, Terrault N, Sax S, Cohen A, et al. Approved All-Oral Sofosbuvir Regimens Are Safe and Highly Effective in Patients With Hereditary Bleeding Disorders. (2015). Hepatology, 62 (S1): 714A-807A. doi:10.1002/hep.28228

*   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: August 25, 2015)
122
Original Estimated Enrollment  ICMJE
 (submitted: April 18, 2014)
125
Actual Study Completion Date  ICMJE August 2015
Actual Primary Completion Date August 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Hemophilia A, B or C, or Von Willebrand's disease
  • Chronic genotype 1, 2, 3 or 4 HCV infection
  • HCV RNA ≥ 1000 IU/mL at screening
  • Use of protocol specified method(s) of contraception if female of childbearing potential or sexually active male
  • Screening laboratory values within defined thresholds
  • For HIV-1/HCV co-infected individuals:

    • Suppressed HIV-1 RNA on an antiretroviral (ARV) regimen for at least 6 months prior to screening
    • Stable protocol-approved ARV regimen for > 8 weeks prior to screening
    • CD4 T-cell count > 200 cells/mm^3 at screening

Exclusion Criteria:

  • Clinically-significant illness (other than HCV, inherited bleeding disorder or HIV-1) or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
  • Current or prior history of any of the following:

    • Hepatic decompensation
    • Chronic liver disease of a non-HCV etiology
    • Hepatocellular carcinoma (HCC)
    • Infection with hepatitis B virus (HBV)
  • Pregnant or nursing female
  • Prior treatment with inhibitors of nonstructural protein 5A (NS5A) or the NS5B polymerase
  • Chronic use of systemically administered immunosuppressive agents
  • For HIV-1/HCV co-infected individuals:

    • Opportunistic infection within 6 months prior to screening
    • Active, serious infection (other than HIV-1 or HCV) requiring parental antibiotics, antivirals or antifungals within 30 days prior to baseline
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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02120300
Other Study ID Numbers  ICMJE GS-US-334-1274
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Robert H Hyland, DPhil Gilead Sciences
PRS Account Gilead Sciences
Verification Date October 2016

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