Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency

HCV Infection Clinical Trial

Official title:

A Phase 2b, Open-Label Study of 200 mg or 400 mg Sofosbuvir+RBV for 24 Weeks in Genotype 1 or 3 and Ledipasvir/Sofosbuvir (LDV/SOF) Fixed Dose Combination (FDC) Tablet for 12 Weeks in Genotype 1 or 4 HCV Infected Subjects With Renal Insufficiency

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01958281
• Other study ID #: GS-US-334-0154
• Secondary ID: 2013-002897-30
• Status: Completed
• Phase: Phase 2
• Start date: October 7, 2013
• Est. completion date: October 19, 2017

Study information

• Verified date: July 2018
• 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 and efficacy of sofosbuvir (SOF) plus ribavirin (RBV) for 24 weeks and ledipasvir/sofosbuvir (LDV/SOF) for 12 weeks, and to evaluate the steady state pharmacokinetics (PK) of SOF and its metabolites and LDV in participants with genotype (GT) 1, 3, or 4 hepatitis C virus (HCV) infection who have chronic renal insufficiency (impaired kidney function).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 38
• Est. completion date: October 19, 2017
• Est. primary completion date: July 18, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Cohorts 1 and 2: chronic genotype 1 or 3 HCV infection

• Cohort 3: chronic genotype 1 or 4 HCV infection

• HCV RNA = 10^4 IU/mL at screening

• Screening labs within defined thresholds

• Cirrhosis determination at screening

Key Exclusion Criteria:

• Females who are pregnant or nursing or males who have a pregnant partner

• Prior null response to pegylated interferon (Peg-IFN)+RBV therapy (Cohorts 1 and 2) or for individuals with cirrhosis, prior treatment failure with IFN-based therapy not resulting from treatment intolerance (Cohort 3)

• Current of prior history of hepatic decompensation

• Infection with hepatitis B virus (HBV) or HIV

• History of clinically significant illness (including psychiatric or cardiac) or any other medical disorder that may interfere with individual's treatment and/or adherence to the protocol

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Related Conditions & MeSH terms

• HCV Infection
• Infection
• Renal Insufficiency

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  New Zealand,  Puerto Rico, 

References & Publications (3)

Gane EJ, Robson RA, Bonacini M, Maliakkal B, Kirby B, Liu L, et al. Safety, Antiviral Efficacy, and Pharmacokinetics of Sofosbuvir in Patients With Severe Renal Impairment [Poster 966]. The 65th Annual meeting of the American Association for the Study of Liver Diseases: The Liver Meeting (AASLD); 2014 November 07-11; Boston, MA.

Lawitz E, Landis CS, Maliakkal BJ, Bonacini M, Ortiz-Lasanta G, Zhang J, et al. Safety and Efficacy of Treatment with Once- Daily Ledipasvir/Sofosbuvir (90/400 mg) for 12 Weeks in Genotype 1 HCV-Infected Patients with Severe Renal Impairment [Abstract 1587]. The Liver Meeting® 2017 - The 68th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD); 2017 20-24 October; Washington, D. C.

Martin P, Gane E, Ortiz-Lasanta G, Liu L, Sajwani K, Kirby B, et al. Safety and Efficacy of Treatment With Daily Sofosbuvir 400 mg + Ribavirin 200 mg for 24 Weeks in Genotype 1 or 3 HCV-Infected Patients With Severe Renal Impairment [Poster 1128]. American Association for the Study of Liver Diseases (AASLD); 2015 November 13-17; San Francisco, CA.

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 HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.	Posttreatment Week 12
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events		Up to 24 weeks plus 30 days
Primary	Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities	Treatment-emergent laboratory abnormalities were defined as values that increased by at least 1 toxicity grade from baseline at any time postbaseline up to the date of last dose of study drug plus 30 days.	Up to 24 weeks plus 30 days
Primary	Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities		Up to 24 weeks plus 30 days
Primary	Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities		Up to 24 weeks plus 30 days
Primary	Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary	PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary	PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Primary	PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Cmax is defined as the maximum concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary	PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Cmax is defined as the maximum concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary	PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Cmax is defined as the maximum concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Primary	PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary	PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary	PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Ctau is defined as the observed drug concentration at the end of the dosing interval.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)	SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.	Posttreatment Week 4
Secondary	Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)	SVR4 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.	Posttreatment Week 24
Secondary	Percentage of Participants With Overall 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.	Up to Posttreatment Week 24
Secondary	PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	AUClast is defined as the concentration of drug from time zero to the last observable concentration.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Clast is defined as the last observable concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Clast is defined as the last observable concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Clast is defined as the last observable concentration of drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Tmax is defined as the time (observed time point) of Cmax.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Tmax is defined as the time (observed time point) of Cmax.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Tmax is defined as the time (observed time point) of Cmax.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	Tlast is defined as the time (observed time point) of Clast.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	Tlast is defined as the time (observed time point) of Clast.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	Tlast is defined as the time (observed time point) of Clast.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	?z is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	?z is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	?z is defined as the terminal elimination rate constant, estimated by linear regression of the terminal elimination phase of the log plasma concentration of drug versus time curve of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary	PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary	PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary	PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)	t1/2 is defined as the estimate of the terminal elimination half-life of the drug.	Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4