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Completed

NCT Number: NCT01958281

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

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).

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Key information

Conditions

HCV Infection Blood-Borne Infections Communicable Diseases Digestive System Diseases Flaviviridae Infections Hepatitis Hepatitis C Hepatitis, Viral, Human Infections Liver Diseases RNA Virus Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Grafton, Auckland, New Zealand

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

SOF

Drug

Tablet(s) administered orally once daily

Other names: Sovaldi®, GS-7977

RBV

Drug

200 mg tablet administered orally once daily

LDV/SOF

Drug

90/400 mg fixed-dose combination (FDC) tablet administered orally once daily

Other names: Harvoni®

Primary outcomes

  1. Percentage of Participants With Sustained Virologic Response (SVR) 12 Weeks After Discontinuation of Therapy (SVR12)

    Time frame: Posttreatment Week 12

    SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ; ie, 15 IU/mL) at 12 weeks after stopping study treatment.

  2. Percentage of Participants Experiencing Treatment-Emergent Adverse Events

    Time frame: Up to 24 weeks plus 30 days

  3. Percentage of Participants Experiencing Treatment-Emergent Laboratory Abnormalities

    Time frame: Up to 24 weeks plus 30 days

    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.

  4. Percentage of Participants Experiencing Clinically Significant 12-lead Electrocardiogram (ECG) Abnormalities

    Time frame: Up to 24 weeks plus 30 days

  5. Percentage of Participants Experiencing Treatment-Emergent Adverse Events Associated With Vital Sign Abnormalities

    Time frame: Up to 24 weeks plus 30 days

  6. Pharmacokinetic (PK) Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  7. PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  8. PK Parameter: AUCtau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval).

  9. PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    Cmax is defined as the maximum concentration of drug.

  10. PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    Cmax is defined as the maximum concentration of drug.

  11. PK Parameter: Cmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    Cmax is defined as the maximum concentration of drug.

  12. PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  13. PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

  14. PK Parameter: Ctau of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    Ctau is defined as the observed drug concentration at the end of the dosing interval.

Secondary outcomes

  1. Percentage of Participants With SVR at 4 Weeks After Discontinuation of Therapy (SVR4)

    Time frame: Posttreatment Week 4

    SVR4 was defined as HCV RNA < LLOQ at 4 weeks after stopping study treatment.

  2. Percentage of Participants With SVR at 24 Weeks After Discontinuation of Therapy (SVR24)

    Time frame: Posttreatment Week 24

    SVR4 was defined as HCV RNA < LLOQ at 24 weeks after stopping study treatment.

  3. Percentage of Participants With Overall Virologic Failure

    Time frame: Up to Posttreatment Week 24

    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.

  4. PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  5. PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  6. PK Parameter: AUClast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    AUClast is defined as the concentration of drug from time zero to the last observable concentration.

  7. PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    Clast is defined as the last observable concentration of drug.

  8. PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    Clast is defined as the last observable concentration of drug.

  9. PK Parameter: Clast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    Clast is defined as the last observable concentration of drug.

  10. PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    Tmax is defined as the time (observed time point) of Cmax.

  11. PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    Tmax is defined as the time (observed time point) of Cmax.

  12. PK Parameter: Tmax of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    Tmax is defined as the time (observed time point) of Cmax.

  13. PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    Tlast is defined as the time (observed time point) of Clast.

  14. PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    Tlast is defined as the time (observed time point) of Clast.

  15. PK Parameter: Tlast of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    Tlast is defined as the time (observed time point) of Clast.

  16. PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    λz 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.

  17. PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    λz 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.

  18. PK Parameter: λz of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    λz 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.

  19. PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 2 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2

    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

  20. PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and RBV at Week 12 (Cohorts 1 and 2)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 12

    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

  21. PK Parameter: t1/2 of SOF, Its Metabolites (GS-566500 and GS-331007), and LDV at Week 2 or 4 (Cohort 3)

    Time frame: Predose, 0.25, 0.5, 1, 2, 4, 6, 8, 10, and 12 hours postdose at Week 2 or 4

    t1/2 is defined as the estimate of the terminal elimination half-life of the drug.

Sponsors and collaborators

Lead sponsor

Gilead Sciences

Industry

Registry information

Official study 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

Important dates

Study start
2013
Primary completion
2017
Study completion
2017
First posted
Oct 9, 2013
Registry last updated
Aug 8, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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