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

• ClinicalTrials.gov Identifier: NCT03036852
• Recruitment Status: Completed
• First Posted: January 30, 2017
• Results First Posted: November 12, 2019
• Last Update Posted: March 6, 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: August 12, 2019
• Results First Posted Date: November 12, 2019
• Last Update Posted Date: March 6, 2020
• Actual Study Start Date: March 22, 2017
• Actual Primary Completion Date: August 13, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: November 5, 2019)

• Percentage of Participants With Sustained Virologic Response 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) 12 weeks after stopping the study treatment.
• Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event [ Time Frame: First dose date up to Week 12 ]

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 12 ]

Current Secondary Outcome Measures (submitted: November 5, 2019)

• Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4) [ Time Frame: Posttreatment Week 4 ]
  SVR4 was defined as HCV RNA < LLOQ 4 weeks after stopping study treatment.
• Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24) [ Time Frame: Posttreatment Week 24 ]
  SVR24 was defined as HCV RNA < LLOQ 24 weeks after stopping study treatment.
• Change From Baseline in HCV RNA [ Time Frame: Baseline; Weeks 2, 4, 6, 8, and 12 ]
• Percentage of Participants With HCV RNA < LLOQ on Treatment [ Time Frame: Weeks 2, 4, 6, 8, and 12 ]
• Percentage of Participants With Virologic Failure [ Time Frame: Baseline 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
• Number of Participants Who Develop Viral Resistance (as Assessed by Presence of HCV NS5A and NS5B Genes) to SOF and VEL During Treatment and After Discontinuation of Treatment [ Time Frame: First dose date up to Posttreatment Week 24 ]
  Baseline deep sequencing of the HCV NS5A and NS5B genes was performed for all participants. For all participants with virologic failure, deep sequencing was performed at the first time point after virologic failure if the plasma or serum sample was available and HCV RNA was > 1000 IU/mL.
• Pharmacokinetic (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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  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 VEL [ 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  AUCtau is defined as the population PK derived area under the concentration verses time curve of the drug over the dosing interval.
• 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  Cmax is defined as the population PK derived maximum concentration of the drug.
• PK Parameter: Cmax of VEL [ 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  Cmax is defined as the population PK derived maximum concentration of the drug.
• PK Parameter: Ctau of VEL [ 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 Week 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=1)) ]
  Ctau is defined as the population PK derived concentration of the drug at the end of a 24 hour dosing interval. The 24 hour Ctau is estimated based on the combination of sparse PK samples collected at random times across the dosing interval as well as intensive PK samples collected for up to 12 hours post-dose.

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 12 ]
• Change From Baseline in HCV RNA [ Time Frame: Up to Week 12 ]
• 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 SOF and VEL During Treatment [ Time Frame: Up to Week 12 ]
• Proportion of Participants Who Develop Resistance to SOF and VEL After Discontinuation of Therapy [ Time Frame: Up to Posttreatment Week 24 ]
• Pharmacokinetic (PK) Parameter: AUCtau of SOF and its metabolites [ Time Frame: Predose and up to 12 hours Postdose ]
• Pharmacokinetic (PK) Parameter: AUCtau of VEL [ 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 ]
• Pharmacokinetic (PK) Parameter: Tmax of VEL [ 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: Sofosbuvir/Velpatasvir in Adults With Chronic Hepatitis C Virus 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 Sofosbuvir/Velpatasvir for 12 Weeks in Subjects With Chronic HCV Infection Who Are on Dialysis for End Stage Renal Disease
• Brief Summary: The primary objectives of this study are to evaluate safety, efficacy, and tolerability of treatment with sofosbuvir/velpatasvir (SOF/VEL) for 12 weeks in adults on dialysis for end stage renal disease (ESRD) with chronic hepatitis C virus (HCV) infection of any genotype.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Hepatitis C

Intervention

Drug: SOF/VEL

400/100 mg fixed-dose combination (FDC) tablet(s) administered orally once daily

Other Names:

• GS-7977/GS-5816
• Epclusa®

Study Arms

Experimental: SOF/VEL

SOF/VEL for 12 weeks

Intervention: Drug: SOF/VEL

Publications *

• Borgia SM, Dearden J, Lurie Y, Shafran SD, Brown A, Hyland RH, et al. Sofosbuvir/Velpatasvir for 12 Weeks Is Safe and Effective in Patients Undergoing Dialysis. American Association for the Study of Liver Diseases (AASLD); 2018 09-13 November; San Francisco, CA.
• Borgia SM, Dearden J, Yoshida EM, Shafran SD, Brown A, Ben-Ari Z, Cramp ME, Cooper C, Foxton M, Rodriguez CF, Esteban R, Hyland R, Lu S, Kirby BJ, Meng A, Markova S, Dvory-Sobol H, Osinusi AO, Bruck R, Ampuero J, Ryder SD, Agarwal K, Fox R, Shaw D, Haider S, Willems B, Lurie Y, Calleja JL, Gane EJ. Sofosbuvir/velpatasvir for 12 weeks in hepatitis C virus-infected patients with end-stage renal disease undergoing dialysis. J Hepatol. 2019 Oct;71(4):660-665. doi: 10.1016/j.jhep.2019.05.028. Epub 2019 Jun 11.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 7, 2018): 59
• Original Estimated Enrollment (submitted: January 27, 2017): 100
• Actual Study Completion Date: November 7, 2018
• Actual Primary Completion Date: August 13, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

• Chronic HCV infected, male and non-pregnant/non-lactating females aged 18 years or older who are on dialysis for ESRD, including adults with HIV co-infection if they are suppressed on a stable, protocol-approved antiretroviral (ARV) regimen 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: Australia, Canada, Israel, New Zealand, Spain, United Kingdom

Administrative Information

• NCT Number: NCT03036852
• Other Study ID Numbers: GS-US-342-4062; 2016-003625-42 ( 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

• 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: Gilead Study Director; Gilead Sciences

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