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

Hepatitis C Virus Infection Clinical Trial

— ESRD  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03036839
• Other study ID #: GS-US-337-4063
• Secondary ID: 2016-003489-25
• Status: Completed
• Phase: Phase 2
• Start date: June 27, 2017
• Est. completion date: February 14, 2019

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 the safety, efficacy and tolerability of treatment with ledipasvir/sofosbuvir (LDV/SOF) in adults with chronic HCV infection who are on dialysis for ESRD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 95
• Est. completion date: February 14, 2019
• Est. primary completion date: November 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C Virus Infection
• Infection
• Kidney Failure, Chronic
• Virus Diseases

Intervention

Drug:
• LDV/SOF
90/400 mg fixed- dose combination (FDC) tablet administered orally once daily

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Taiwan, 

References & Publications (1)

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.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	Percentage of Participants Who Permanently Discontinued Study Drug Due to an Adverse Event		First dose date up to Week 24
Secondary	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
Secondary	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
Secondary	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
Secondary	HCV RNA		Weeks 2, 4, 6, 8, 12, 16, 20, 24
Secondary	Change From Baseline in HCV RNA		Weeks 2, 4, 6, 8, 12, 16, 20, 24
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 up to Posttreatment Week 24
Secondary	Percentage of Participants Who Developed Resistance to LDV and SOF		Baseline up to Posttreatment Week 24
Secondary	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))
Secondary	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))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
Secondary	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))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))
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 Weeks 6, 8, or 12 (participants who enrolled in the optional PK substudy (N=2))