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

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT01958281
First received: October 6, 2013
Last updated: February 24, 2017
Last verified: February 2017

October 6, 2013
February 24, 2017
October 7, 2013
July 2017   (Final data collection date for primary outcome measure)
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of treatment (SVR12) [ Time Frame: Posttreatment Week 12 ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study drug.
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Up to 12 or 24 weeks plus 30 days ]
  • Plasma pharmacokinetics (PK) of sofosbuvir and its metabolites, LDV, and RBV, including AUCtau, Cmax, and Ctau [ Time Frame: Up to 12 or 24 weeks ]
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • Cmax is defined as the maximum concentration of drug
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
  • Proportion of participants with sustained virologic response 12 weeks after discontinuation of treatment (SVR12) [ Time Frame: Post-treatment Week 12 ]
    SVR12 is defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, < 25 IU/mL) 12 weeks following the last dose of study medication.
  • Number of Participants with Adverse Events as a Measure of Safety and Tolerability [ Time Frame: Baseline to Week 24 plus 30 days ]
  • Plasma pharmacokinetics (PK) of sofosbuvir and its metabolites, and RBV, including AUCtau, Cmax, and Ctau [ Time Frame: Baseline to Week 24 ]
    • AUCtau is defined as the concentration of drug over time (area under the plasma concentration versus time curve over the dosing interval)
    • Cmax is defined as the maximum concentration of drug
    • Ctau is defined as the observed drug concentration at the end of the dosing interval
Complete list of historical versions of study NCT01958281 on ClinicalTrials.gov Archive Site
  • Plasma pharmacokinetics (PK) of sofosbuvir and its metabolites, LDV, and RBV, including AUClast, Clast, Tmax, Tlast, λz, and t1/2 [ Time Frame: Up to 12 or 24 weeks ]
    • AUClast is defined as the concentration of drug from time zero to the last observable concentration
    • Clast is defined as the last observable concentration of drug
    • Tmax is defined as the time of Cmax
    • Tlast is defined as the time of Clast
    • λz is defined as the terminal elimination rate constant
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug
  • Proportion of participants with sustained virologic response 4 and 24 weeks after discontinuation of treatment (SVR4 and SVR 24) [ Time Frame: Posttreatment Weeks 4 and 24 ]
  • Proportion of participants with virologic failure [ Time Frame: Up to Posttreatment Week 24 ]

    Virologic failure will be measured by incidence of viral breakthrough and viral relapse.

    • Viral breakthrough is defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.
    • Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.
  • Plasma pharmacokinetics (PK) of sofosbuvir and its metabolites, and RBV, including AUClast, Clast, Tmax, Tlast, λz, and t1/2 [ Time Frame: Baseline to Week 24 ]
    • AUClast is defined as the concentration of drug from time zero to the last observable concentration
    • Clast is defined as the last observable concentration of drug
    • Tmax is defined as the time of Cmax
    • Tlast is defined as the time of Clast
    • λz is defined as the terminal elimination rate constant
    • t1/2 is defined as the estimate of the terminal elimination half-life of the drug
  • Proportion of participants with sustained virologic response 4 and 24 weeks after discontinuation of treatment (SVR4 and SVR 24) [ Time Frame: Post-treatment Weeks 4 and 24 ]
  • Proportion of participants with virologic failure [ Time Frame: Baseline to Post-treatment Week 24 ]

    Virologic failure will be measured by incidence of viral breakthrough and viral relapse.

    • Viral breakthrough is defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be post-treatment), or last available on-treatment measurement with no subsequent follow-up values.
    • Viral relapse is defined as HCV RNA ≥ LLOQ during the post-treatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available post-treatment measurement.
Not Provided
Not Provided
 
Sofosbuvir Plus Ribavirin, or Ledipasvir/Sofosbuvir in Adults With HCV Infection and Renal Insufficiency
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

This study will evaluate the safety, tolerability and antiviral efficacy of sofosbuvir (SOF) with ribavirin (RBV) in participants with GT 1 and 3 and ledipasvir (LDV)/SOF in participants with genotype 1 and 4 HCV infection who have chronic renal insufficiency (impaired kidney function).

Approximately 35 subjects with severe renal insufficiency (not on dialysis) will be enrolled in 3 cohorts.

  • Cohort 1 (GT 1 or 3): 10 subjects will receive SOF 200 mg + RBV 200 mg once daily for 24 weeks.
  • Cohort 2 (GT 1 or 3): Following review of safety, efficacy and pharmacokinetics (PK) data through post-treatment Week 4 of Cohort 1, 10 additional subjects will receive SOF 400 mg + RBV 200 mg once daily for 24 weeks.
  • Cohort 3 (GT 1 or 4): Following review of safety and available PK data through Week 12 of Cohort 2, 15 additional subjects will receive LDV/SOF 90/400 mg once daily for 12 weeks.
Not Provided
Interventional
Phase 2
Allocation: Non-Randomized
Masking: No masking
Primary Purpose: Treatment
HCV Infection
  • Drug: SOF 100 mg
    Sofosbuvir (SOF) 100 mg tablets administered orally once daily
    Other Name: GS-7977
  • Drug: SOF 400 mg
    SOF 400 mg tablet administered orally once daily
    Other Names:
    • Sovaldi®
    • GS-7977
  • Drug: RBV
    Ribavirin (RBV) 200 mg tablet administered orally once daily
  • Drug: LDV/SOF
    Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet administered orally once daily
    Other Name: Harvoni®
  • Experimental: Cohort 1
    10 participants with genotype 1 or 3 HCV infection will receive SOF 200 mg (as 2 × 100 mg tablets) plus RBV once daily for 24 weeks.
    Interventions:
    • Drug: SOF 100 mg
    • Drug: RBV
  • Experimental: Cohort 2
    10 participants with genotype 1 or 3 HCV infection will receive SOF 400 mg (as 4 × 100 mg tablets or 1 × 400 mg tablet) plus RBV once daily for 24 weeks.
    Interventions:
    • Drug: SOF 100 mg
    • Drug: SOF 400 mg
    • Drug: RBV
  • Experimental: Cohort 3
    15 participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.
    Intervention: Drug: LDV/SOF
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
38
October 2017
July 2017   (Final data collection date for primary outcome measure)

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 PEG+RBV therapy
  • 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.

Sexes Eligible for Study: All
18 Years and older   (Adult, Senior)
No
Contact information is only displayed when the study is recruiting subjects
United States,   New Zealand,   Puerto Rico
Argentina,   Austria,   Germany,   Netherlands
 
NCT01958281
GS-US-334-0154
2013-002897-30 ( EudraCT Number )
No
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Not Provided
Not Provided
Gilead Sciences
Gilead Sciences
Not Provided
Study Director: Gilead Study Director Gilead Sciences
Gilead Sciences
February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP