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

Chronic Hepatitis C Clinical Trial

— SOF/VEL ESRD  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03036852
• Other study ID #: GS-US-342-4062
• Secondary ID: 2016-003625-42
• Status: Completed
• Phase: Phase 2
• Start date: March 22, 2017
• Est. completion date: November 7, 2018

Study information

• Verified date: November 2019
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: November 7, 2018
• Est. primary completion date: August 13, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Kidney Failure, Chronic

Intervention

Drug:
• SOF/VEL
400/100 mg fixed-dose combination (FDC) tablet(s) administered orally once daily

Locations

Country	Name	City	State
Australia	Royal Adelaide Hospital	Adelaide	South Australia
Canada	William Osler Health System- Brampton Civic Hospital	Brampton	Ontario
Canada	Kaye Edmonton Clinic	Edmonton	Alberta
Canada	Hamilton Health Sciences - McMaster University Medical Centre Site	Hamilton	Ontario
Canada	Centre de Recherche du Centre Hospitalier de l'Universite de Montreal (CRCHUM)	Montréal	Quebec
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Gordon and Leslie Diamond Health Care Center, Vancouver General Hospital, UBC Division of Gastroenterology	Vancouver	British Columbia
Israel	Shaare Zedek Medical Center	Jerusalem
Israel	The Chaim Sheba Medical Centre	Ramat Gan
Israel	Tel Aviv Sourasky Medical Center	Tel Aviv
New Zealand	Auckland City Hospital	Grafton	Auckland
Spain	Hospital Universitario Fundación Alcorcón	Alcorcón	Madrid
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda
Spain	Hospital Universitario Virgen del Rocío	Sevilla
United Kingdom	Gartnavel General Hospital	Glasgow
United Kingdom	Barts Health NHS Trust	London
United Kingdom	Chelsea and Westminster Hospital	London
United Kingdom	Imperial College Healthcare NHS Trust	London
United Kingdom	King's College Hospital	London
United Kingdom	Nottingham University Hospitals NHS Trust	Nottingham
United Kingdom	Derriford Hospital	Plymouth

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

Australia,  Canada,  Israel,  New Zealand,  Spain,  United Kingdom, 

References & Publications (1)

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 Francis

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Sustained Virologic Response 12 Weeks After Discontinuation of Therapy (SVR12)	SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) 12 weeks after stopping the study treatment.	Posttreatment Week 12
Primary	Percentage of Participants Who Permanently Discontinued the Study Drug Due to an Adverse Event		First dose date up to Week 12
Secondary	Percentage of Participants With Sustained Virologic Response 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ 4 weeks after stopping study treatment.	Posttreatment Week 4
Secondary	Percentage of Participants With Sustained Virologic Response 24 Weeks After Discontinuation of Therapy (SVR24)	SVR24 was defined as HCV RNA < LLOQ 24 weeks after stopping study treatment.	Posttreatment Week 24
Secondary	Change From Baseline in HCV RNA		Baseline; Weeks 2, 4, 6, 8, and 12
Secondary	Percentage of Participants With HCV RNA < LLOQ on Treatment		Weeks 2, 4, 6, 8, and 12
Secondary	Percentage of Participants With Virologic Failure	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	Baseline to Posttreatment Week 24
Secondary	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	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.	First dose date up to Posttreatment Week 24
Secondary	Pharmacokinetic (PK) Parameter: AUCtau of SOF	AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.	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))
Secondary	PK Parameter: AUCtau of GS-331007 (Metabolite of SOF)	AUCtau is defined as the population PK derived area under the concentration versus time curve of the drug over the dosing interval.	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))
Secondary	PK Parameter: AUCtau of VEL	AUCtau is defined as the population PK derived area under the concentration verses time curve of the drug over the dosing interval.	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))
Secondary	PK Parameter: Cmax of SOF	Cmax is defined as the population PK derived maximum concentration of the drug.	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))
Secondary	PK Parameter: Cmax of GS-331007 (Metabolite of SOF)	Cmax is defined as the population PK derived maximum concentration of the drug.	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))
Secondary	PK Parameter: Cmax of VEL	Cmax is defined as the population PK derived maximum concentration of the drug.	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))
Secondary	PK Parameter: Ctau of VEL	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.	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))