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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01958281




Registration number
NCT01958281
Ethics application status
Date submitted
6/10/2013
Date registered
9/10/2013
Date last updated
8/08/2018

Titles & IDs
Public title
Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency
Scientific 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
Secondary ID [1] 0 0
2013-002897-30
Secondary ID [2] 0 0
GS-US-334-0154
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
HCV Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Renal and Urogenital 0 0 0 0
Kidney disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - SOF
Treatment: Drugs - RBV
Treatment: Drugs - LDV/SOF

Experimental: SOF 200 mg + RBV 200 mg (Cohort 1) - Participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (2 × 100 mg tablets) plus RBV once daily for 24 weeks.

Experimental: SOF 400 mg + RBV 200 mg (Cohort 2) - Participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.

Experimental: LDV/SOF (Cohort 3) - Participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.


Treatment: Drugs: SOF
Tablet(s) administered orally once daily

Treatment: Drugs: RBV
200 mg tablet administered orally once daily

Treatment: Drugs: LDV/SOF
90/400 mg fixed-dose combination (FDC) tablet administered orally once daily
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)
Timepoint [1] 0 0
Posttreatment Week 12
Primary outcome [2] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Timepoint [2] 0 0
Up to 24 weeks plus 30 days
Primary outcome [3] 0 0
Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities
Timepoint [3] 0 0
Up to 24 weeks plus 30 days
Primary outcome [4] 0 0
Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities
Timepoint [4] 0 0
Up to 24 weeks plus 30 days
Primary outcome [5] 0 0
Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities
Timepoint [5] 0 0
Up to 24 weeks plus 30 days
Primary outcome [6] 0 0
Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [6] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary outcome [7] 0 0
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [7] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary outcome [8] 0 0
PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [8] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Primary outcome [9] 0 0
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [9] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary outcome [10] 0 0
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [10] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary outcome [11] 0 0
PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [11] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Primary outcome [12] 0 0
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [12] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Primary outcome [13] 0 0
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [13] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Primary outcome [14] 0 0
PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [14] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [1] 0 0
Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)
Timepoint [1] 0 0
Posttreatment Week 4
Secondary outcome [2] 0 0
Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)
Timepoint [2] 0 0
Posttreatment Week 24
Secondary outcome [3] 0 0
Percentage of Participants With Overall Virologic Failure
Timepoint [3] 0 0
Up to Posttreatment Week 24
Secondary outcome [4] 0 0
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [4] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [5] 0 0
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [5] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [6] 0 0
PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [6] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [7] 0 0
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [7] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [8] 0 0
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [8] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [9] 0 0
PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [9] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [10] 0 0
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [10] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [11] 0 0
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [11] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [12] 0 0
PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [12] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [13] 0 0
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [13] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [14] 0 0
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [14] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [15] 0 0
PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [15] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [16] 0 0
PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [16] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [17] 0 0
PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [17] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [18] 0 0
PK Parameter: ?z of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [18] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4
Secondary outcome [19] 0 0
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)
Timepoint [19] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2
Secondary outcome [20] 0 0
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)
Timepoint [20] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12
Secondary outcome [21] 0 0
PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)
Timepoint [21] 0 0
Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

Eligibility
Key inclusion criteria
Key

* 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
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.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
7/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
19/10/2017
Sample size
Target
Accrual to date
Final
38
Recruitment in Australia
Recruitment state(s)
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Illinois
Country [4] 0 0
United States of America
State/province [4] 0 0
Michigan
Country [5] 0 0
United States of America
State/province [5] 0 0
New York
Country [6] 0 0
United States of America
State/province [6] 0 0
Texas
Country [7] 0 0
United States of America
State/province [7] 0 0
Washington
Country [8] 0 0
New Zealand
State/province [8] 0 0
Auckland
Country [9] 0 0
New Zealand
State/province [9] 0 0
Christchurch
Country [10] 0 0
Puerto Rico
State/province [10] 0 0
San Juan

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Gilead Sciences
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT01958281
Trial related presentations / publications
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.
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.
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.
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.
Public notes

Contacts
Principal investigator
Name 0 0
Gilead Study Director
Address 0 0
Gilead Sciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01958281