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Ledipasvir/Sofosbuvir in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Are on Dialysis for End Stage Renal Disease (ESRD)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03036839
Recruitment Status : Completed
First Posted : January 30, 2017
Results First Posted : December 9, 2019
Last Update Posted : March 2, 2020
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences

Tracking Information
First Submitted Date  ICMJE January 27, 2017
First Posted Date  ICMJE January 30, 2017
Results First Submitted Date  ICMJE November 15, 2019
Results First Posted Date  ICMJE December 9, 2019
Last Update Posted Date March 2, 2020
Actual Study Start Date  ICMJE June 27, 2017
Actual Primary Completion Date November 22, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
  • Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 was defined as hepatitis C virus ribonucleic acid (HCV RNA) < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment. The exact 95% confidence interval (CI) for the percentage within treatment group was based on the Clopper-Pearson method.
  • Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event [ Time Frame: First dose date up to Week 24 ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
  • 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.
  • Proportion of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event [ Time Frame: Up to Week 24 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 15, 2019)
  • 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 (ie, 15 IU/mL) at 4 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
  • Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 was defined as HCV RNA < LLOQ (ie, 15 IU/mL) at 24 weeks after stopping study treatment. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
  • Percentage of Participants With HCV RNA < LLOQ on Treatment [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24 ]
    The total number of participants with HCV RNA < LLOQ was the sum of the number of participants with HCV RNA "< LLOQ detected" plus the number of participants with HCV RNA "< LLOQ target not detected (TND)". LLOQ was 15 IU/mL. The exact 95% CI for the percentage within treatment group was based on the Clopper-Pearson method.
  • HCV RNA [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24 ]
  • Change From Baseline in HCV RNA [ Time Frame: Weeks 2, 4, 6, 8, 12, 16, 20, 24 ]
  • Percentage of Participants With Virologic Failure [ Time Frame: Baseline 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 Who Developed Resistance to LDV and SOF [ Time Frame: Baseline up to Posttreatment Week 24 ]
  • Pharmacokinetics (PK) Parameter: AUCtau of LDV [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.
  • PK Parameter: AUCtau of SOF [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.
  • PK Parameter: AUCtau of GS-331007 (Metabolite of SOF) [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.
  • PK Parameter: Cmax of LDV [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    Cmax is defined as the population PK derived maximum concentration of the drug.
  • PK Parameter: Cmax of SOF [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    Cmax is defined as the population PK derived maximum concentration of the drug.
  • PK Parameter: Cmax of GS-331007 (Metabolite of SOF) [ Time Frame: Sparse PK Samples at Weeks 6, 8, and 12 (all participants). Intensive PK samples at predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose once at Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2)) ]
    Cmax is defined as the population PK derived maximum concentration of the drug.
Original Secondary Outcome Measures  ICMJE
 (submitted: January 27, 2017)
  • Proportion of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
    SVR4 is defined as HCV RNA < LLOQ 4 weeks after the last dose of study drug.
  • Proportion of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
    SVR24 is defined as HCV RNA < LLOQ 24 weeks after the last dose of study drug.
  • Proportion of participants with HCV RNA < LLOQ on treatment [ Time Frame: Up to Week 24 ]
  • Change From Baseline in HCV RNA [ Time Frame: Up to Week 24 ]
  • Proportion of Participants With Virologic Failure [ Time Frame: Up to Posttreatment Week 24 ]
    Virologic failure is 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.
  • Proportion of Participants Who Develop Resistance to LDV and SOF During Treatment [ Time Frame: Up to Week 24 ]
  • Proportion of Participants Who Develop Resistance to LDV and SOF After Discontinuation of Therapy [ Time Frame: Up to Posttreatment Week 24 ]
  • Pharmacokinetic (PK) Parameter: AUCtau of LDV [ Time Frame: Predose and up to 12 hours Postdose ]
  • Pharmacokinetic (PK) Parameter: AUCtau of SOF and its metabolites [ Time Frame: Predose and up to 12 hours Postdose ]
  • Pharmacokinetic (PK) Parameter: Tmax of LDV [ Time Frame: Predose and up to 12 hours Postdose ]
  • Pharmacokinetic (PK) Parameter: Tmax of SOF and its metabolites [ Time Frame: Predose and up to 12 hours Postdose ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Ledipasvir/Sofosbuvir in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Are on Dialysis for End Stage Renal Disease
Official Title  ICMJE A Phase 2, Multicenter, Open-Label Study to Evaluate the Efficacy and Safety of Ledipasvir/Sofosbuvir in Subjects With Genotype 1, 4, 5 and 6 Chronic HCV Infection Who Are on Dialysis for End Stage Renal Disease
Brief Summary The primary objectives of this study are to evaluate the safety, efficacy and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) in adults with chronic HCV infection who are on dialysis for ESRD.
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 Hepatitis C Virus Infection
Intervention  ICMJE Drug: LDV/SOF
90/400 mg fixed- dose combination (FDC) tablet administered orally once daily
Other Names:
  • Harvoni®
  • GS-5885/GS-7977
Study Arms  ICMJE
  • Experimental: LDV/SOF for 8 weeks
    Treatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF for 12 weeks
    Treatment-experienced participants with genotype 1 and treatment-naive or treatment-experienced participants with genotype 2 (Taiwan only), 4, 5 and 6 without cirrhosis will receive LDV/SOF for 12 weeks
    Intervention: Drug: LDV/SOF
  • Experimental: LDV/SOF for 24 weeks
    Participants with compensated cirrhosis will receive LDV/SOF for 24 weeks
    Intervention: Drug: LDV/SOF
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: April 5, 2018)
95
Original Estimated Enrollment  ICMJE
 (submitted: January 27, 2017)
100
Actual Study Completion Date  ICMJE February 14, 2019
Actual Primary Completion Date November 22, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Key Inclusion Criteria:

  • Chronic HCV infected genotype 1, 2 (Taiwan only), 4, 5, or 6 male and nonpregnant/ nonlactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV coinfection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimens for ≥8 weeks prior to screening.

NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

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 Belgium,   Germany,   Italy,   Taiwan,   United States
Removed Location Countries Switzerland
 
Administrative Information
NCT Number  ICMJE NCT03036839
Other Study ID Numbers  ICMJE GS-US-337-4063
2016-003489-25 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
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 https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy.
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: https://www.gilead.com/science-and-medicine/research/clinical-trials-transparency-and-data-sharing-policy
Responsible Party Gilead Sciences
Study Sponsor  ICMJE Gilead Sciences
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Gilead Study Director Gilead Sciences
PRS Account Gilead Sciences
Verification Date November 2019

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