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

• 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: Gilead Sciences
• Information provided by (Responsible Party): Gilead Sciences

Tracking Information

• First Submitted Date: January 27, 2017
• First Posted Date: January 30, 2017
• Results First Submitted Date: November 15, 2019
• Results First Posted Date: December 9, 2019
• Last Update Posted Date: March 2, 2020
• Actual Study Start Date: June 27, 2017
• Actual Primary Completion Date: November 22, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (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 (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 ]

Current Secondary Outcome Measures (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 (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: Ledipasvir/Sofosbuvir in Adults With Chronic Hepatitis C Virus (HCV) Infection Who Are on Dialysis for End Stage Renal Disease
• Official Title: 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: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Hepatitis C Virus Infection

Intervention

Drug: LDV/SOF

90/400 mg fixed- dose combination (FDC) tablet administered orally once daily

Other Names:

• Harvoni®
• GS-5885/GS-7977

Study Arms

• 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 *

• Chuang W-L, Hu T-H, Buggisch P, et al. Ledipasvir/sofosbuvir for 8, 12, or 24 weeks is safe and effective in patients undergoing dialysis. J Hepatol 2019;70 (Suppl 1S):e225.
• Chuang WL, Hu TH, Buggisch P, Moreno C, Su WW, Biancone L, Camargo M, Hyland R, Lu S, Kirby BJ, Dvory-Sobol H, Osinusi A, Gaggar A, Peng CY, Liu CH, Sise ME, Mangia A. Ledipasvir/Sofosbuvir for 8, 12, or 24 Weeks in Hepatitis C Patients Undergoing Dialysis for End-Stage Renal Disease. Am J Gastroenterol. 2021 Sep 1;116(9):1924-1928. doi: 10.14309/ajg.0000000000001281.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 5, 2018): 95
• Original Estimated Enrollment (submitted: January 27, 2017): 100
• Actual Study Completion Date: February 14, 2019
• Actual Primary Completion Date: November 22, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

• 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: Belgium, Germany, Italy, Taiwan, United States
• Removed Location Countries: Switzerland

Administrative Information

• NCT Number: NCT03036839
• Other Study ID Numbers: 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

• 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: Gilead Sciences
• Collaborators: Not Provided

Investigators

• Study Director: Gilead Study Director; Gilead Sciences

• PRS Account: Gilead Sciences
• Verification Date: November 2019