Clinical trial NCT01958281: Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: HCV Infection
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2013-10-09
Enrollment: 38
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief 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).


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
timeFrame: Posttreatment Week 12
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events
timeFrame: Up to 24 weeks plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
timeFrame: Up to 24 weeks plus 30 days
measure: Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities
timeFrame: Up to 24 weeks plus 30 days
measure: Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities
timeFrame: Up to 24 weeks plus 30 days
measure: Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcomes:
measure: Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
timeFrame: Posttreatment Week 4
measure: Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
timeFrame: Posttreatment Week 24
measure: Percentage of Participants With Overall Virologic Failure
timeFrame: Up to Posttreatment Week 24
measure: PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
measure: PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
measure: PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
measure: PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
timeFrame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Other outcomes:
Locations:
city: San Francisco
country: United States
state: California
city: Miami
country: United States
state: Florida
city: Chicago
country: United States
state: Illinois
city: Detroit
country: United States
state: Michigan
city: Rochester
country: United States
state: New York
city: San Antonio
country: United States
state: Texas
city: Seattle
country: United States
state: Washington
city: Grafton
country: New Zealand
state: Auckland
city: Christchurch
country: New Zealand
city: San Juan
country: Puerto Rico
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: Lawitz E, Landis CS, Flamm SL, Bonacini M, Ortiz-Lasanta G, Huang J, Zhang J, Kirby BJ, De-Oertel S, Hyland RH, Osinusi AO, Brainard DM, Robson R, Maliakkal BJ, Gordon SC, Gane EJ. Sofosbuvir plus ribavirin and sofosbuvir plus ledipasvir in patients with genotype 1 or 3 hepatitis C virus and severe renal impairment: a multicentre, phase 2b, non-randomised, open-label study. Lancet Gastroenterol Hepatol. 2020 Oct;5(10):918-926. doi: 10.1016/S2468-1253(19)30417-0. Epub 2020 Jun 10.