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

Phase 2
Completed
Conditions
Chronic Hepatitis C
Interventions
Registration Number
NCT03036852
Lead Sponsor
Gilead Sciences
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 available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
59
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.

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
SOF/VELSOF/VELSOF/VEL for 12 weeks
Primary Outcome Measures
NameTimeMethod
Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)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 EventFirst dose date up to Week 12
Secondary Outcome Measures
NameTimeMethod
PK Parameter: AUCtau of GS-331007 (Metabolite of SOF)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.

Change From Baseline in HCV RNABaseline; Weeks 2, 4, 6, 8, and 12
Percentage of Participants With HCV RNA < LLOQ on TreatmentWeeks 2, 4, 6, 8, and 12
PK Parameter: Cmax of SOFSparse 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.

Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)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)Posttreatment Week 24

SVR24 was defined as HCV RNA \< LLOQ 24 weeks after stopping study treatment.

Percentage of Participants With Virologic FailureBaseline 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 TreatmentFirst 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 SOFSparse 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 VELSparse 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 GS-331007 (Metabolite of SOF)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 VELSparse 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 VELSparse 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.

Trial Locations

Locations (22)

Shaare Zedek Medical Center

🇮🇱

Jerusalem, Israel

Auckland City Hospital

🇳🇿

Grafton, Auckland, New Zealand

Chelsea and Westminster Hospital

🇬🇧

London, United Kingdom

Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)

🇨🇦

Montréal, Quebec, Canada

Tel Aviv Sourasky Medical Center

🇮🇱

Tel Aviv, Israel

Hamilton Health Sciences - McMaster University Medical Centre Site

🇨🇦

Hamilton, Ontario, Canada

Hospital Universitario Fundación Alcorcón

🇪🇸

Alcorcón, Madrid, Spain

Gordon and Leslie Diamond Health Care Center, Vancouver General Hospital, UBC Division of Gastroenterology

🇨🇦

Vancouver, British Columbia, Canada

Barts Health NHS Trust

🇬🇧

London, United Kingdom

Hospital Universitario Virgen del Rocío

🇪🇸

Sevilla, Spain

Kaye Edmonton Clinic

🇨🇦

Edmonton, Alberta, Canada

Ottawa Hospital Research Institute

🇨🇦

Ottawa, Ontario, Canada

Royal Adelaide Hospital

🇦🇺

Adelaide, South Australia, Australia

William Osler Health System- Brampton Civic Hospital

🇨🇦

Brampton, Ontario, Canada

Imperial College Healthcare NHS Trust

🇬🇧

London, United Kingdom

Nottingham University Hospitals NHS Trust

🇬🇧

Nottingham, United Kingdom

Derriford Hospital

🇬🇧

Plymouth, United Kingdom

King's College Hospital

🇬🇧

London, United Kingdom

The Chaim Sheba Medical Centre

🇮🇱

Ramat Gan, Israel

Hospital Universitario Puerta de Hierro - Majadahonda

🇪🇸

Majadahonda, Spain

Hospital Universitari Vall d'Hebron

🇪🇸

Barcelona, Spain

Gartnavel General Hospital

🇬🇧

Glasgow, United Kingdom

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