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

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

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.

Study Overview

• Status: Completed
• Conditions: Hepatitis C Virus Infection
• Intervention / Treatment: Drug: LDV/SOF

• Study Type: Interventional
• Enrollment (Actual): 95
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1070
    • CUB Hôpital Erasme
  • Brussels, Belgium, 1200
    • Cliniques Universitaires Ucl Saint-Luc
• Germany
  • Frankfurt, Germany, 60590
    • Klinikum der Johann Wolfgang Goethe-Universität
  • Hamburg, Germany, 20246
    • Universitatsklinikum Hamburg-Eppendorf (UKE), Zentrum fur Innere Medizin - Studienambulanz Hepatol.
  • Hamburg, Germany, 20251
    • Ifi Studien und Projekt GmbH an der Asklepios Klinik St. Georg
  • Leipzig, Germany, 04103
    • Universitätsklinikum Leipzig
• Italy
  • Antella, Italy, 50011
    • Ospedale Santa Maria Annunziata
  • Milan, Italy, 20122
    • Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico
  • Torino, Italy, 10126
    • Azienda Ospedaliera Città della Salute e della Scienza di Torino
  • Foggia
    • San Giovanni Rotondo, Foggia, Italy, 71013
      • IRCCS Ospedale Casa Sollievo Della Sofferrenza
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung, Taiwan, 80756
    • Kaohsiung Medical University Chung-Ho Memorial Hospital
  • Kaohsiung, Taiwan, 83301
    • Chang Gung Medical Foundation, Kaohsiung Chang Gung Memorial Hospital
  • Taichung, Taiwan, 40447
    • China Medical University Hospital
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital
• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • New York
    • Bronx, New York, United States, 10468
      • James J. Peters VA Hospital
  • Texas
    • Dallas, Texas, United States, 75203
      • The Liver Institute at Methodist Dallas Medical Center
    • San Antonio, Texas, United States, 78215
      • Texas Liver Institute/American Research Corporation
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington/Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LDV/SOF for 8 weeks; Treatment-naive participants with genotype 1 without cirrhosis will receive LDV/SOF for 8 weeks	Drug: LDV/SOF; 90/400 mg fixed- dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
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	Drug: LDV/SOF; 90/400 mg fixed- dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977
Experimental: LDV/SOF for 24 weeks; Participants with compensated cirrhosis will receive LDV/SOF for 24 weeks	Drug: LDV/SOF; 90/400 mg fixed- dose combination (FDC) tablet administered orally once daily; Other Names: Harvoni®; GS-5885/GS-7977

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)	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.	Posttreatment Week 12
Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event		First dose date up to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	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.	Posttreatment Week 4
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	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.	Posttreatment Week 24
Percentage of Participants With HCV RNA < LLOQ on Treatment	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.	Weeks 2, 4, 6, 8, 12, 16, 20, 24
HCV RNA		Weeks 2, 4, 6, 8, 12, 16, 20, 24
Change From Baseline in HCV RNA		Weeks 2, 4, 6, 8, 12, 16, 20, 24
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), orRebound (confirmed > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment), orNon-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 up to Posttreatment Week 24
Percentage of Participants Who Developed Resistance to LDV and SOF		Baseline up to Posttreatment Week 24
Pharmacokinetics (PK) Parameter: AUCtau of LDV	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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
PK Parameter: Cmax of LDV	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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))

Collaborators and Investigators

• Sponsor: Gilead Sciences

Publications and helpful links

General 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2017
• Primary Completion (Actual): November 22, 2018
• Study Completion (Actual): February 14, 2019

Study Registration Dates

• First Submitted: January 27, 2017
• First Submitted That Met QC Criteria: January 27, 2017
• First Posted (Estimate): January 30, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2020
• Last Update Submitted That Met QC Criteria: February 18, 2020
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Kidney Diseases; Urologic Diseases; Disease Attributes; Liver Diseases; Renal Insufficiency; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Renal Insufficiency, Chronic; Infections; Communicable Diseases; Hepatitis; Hepatitis A; Hepatitis C; Kidney Failure, Chronic; Anti-Infective Agents; Antiviral Agents; Sofosbuvir; Ledipasvir, sofosbuvir drug combination; Ledipasvir
• Other Study ID Numbers: GS-US-337-4063; 2016-003489-25 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD 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.
• IPD Sharing Time Frame: 18 months after study completion
• IPD Sharing Access Criteria: A secured external environment with username, password, and RSA code.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• 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