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

Phase 2

Completed

Conditions: Hepatitis C Virus Infection

Interventions: Drug: LDV/SOF

Registration Number: NCT03036839

Lead Sponsor: Gilead Sciences

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 available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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.

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDV/SOF for 8 weeks	LDV/SOF	Treatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks
LDV/SOF for 12 weeks	LDV/SOF	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
LDV/SOF for 24 weeks	LDV/SOF	Participants with compensated cirrhosis will receive LDV/SOF for 24 weeks

Primary Outcome Measures

Name	Time	Method
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	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	First dose date up to Week 24

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	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 HCV RNA < LLOQ on Treatment	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.
Change From Baseline in HCV RNA	Weeks 2, 4, 6, 8, 12, 16, 20, 24
Percentage of Participants With Virologic Failure	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	Baseline up to Posttreatment Week 24
Pharmacokinetics (PK) Parameter: AUCtau of LDV	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	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.
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	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.
HCV RNA	Weeks 2, 4, 6, 8, 12, 16, 20, 24
PK Parameter: Cmax of LDV	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	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)	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: 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 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.

Trial Locations

Locations (21): Massachusetts General Hospital
🇺🇸
Boston, Massachusetts, United States
Henry Ford Health System
🇺🇸
Detroit, Michigan, United States
James J. Peters VA Hospital
🇺🇸
Bronx, New York, United States
Texas Liver Institute/American Research Corporation
🇺🇸
San Antonio, Texas, United States
University of Washington/Harborview Medical Center
🇺🇸
Seattle, Washington, United States
CUB Hopital Erasme
🇧🇪
Brussels, Belgium
Klinikum der Johann Wolfgang Goethe-Universität
🇩🇪
Frankfurt, Germany
Cliniques Universitaires UCL Saint-Luc
🇧🇪
Brussels, Belgium
Universitatsklinikum Hamburg-Eppendorf (UKE), Zentrum fur Innere Medizin - Studienambulanz Hepatol.
🇩🇪
Hamburg, Germany
IRCCS Ospedale Casa Sollievo Della Sofferrenza
🇮🇹
San Giovanni Rotondo, Foggia, Italy
Ifi Studien und Projekt GmbH an der Asklepios Klinik St. Georg
🇩🇪
Hamburg, Germany
Universitätsklinikum Leipzig
🇩🇪
Leipzig, Germany
Ospedale Santa Maria Annunziata
🇮🇹
Antella, Italy
Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico
🇮🇹
Milan, Italy
Kaohsiung Medical University Chung-Ho Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
Changhua Christian Hospital
🇨🇳
Changhua, Taiwan
Azienda Ospedaliera Città della Salute e della Scienza di Torino
🇮🇹
Torino, Italy
Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
🇨🇳
Kaohsiung, Taiwan
China Medical University Hospital
🇨🇳
Taichung, Taiwan
National Taiwan University Hospital
🇨🇳
Taipei, Taiwan
The Liver Institute at Methodist Dallas Medical Center
🇺🇸
Dallas, Texas, United States