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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: August 15, 2017
Last verified: August 2017
  Purpose

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.

Condition Intervention Phase
HCV Infection Drug: SOF 100 mg Drug: SOF 400 mg Drug: RBV Drug: LDV/SOF Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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


Secondary Outcome Measures:
  • 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.


Enrollment: 38
Actual Study Start Date: October 7, 2013
Estimated Study Completion Date: October 2017
Primary Completion Date: July 18, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: SOF 100 mg
Sofosbuvir (SOF) 100 mg tablets administered orally once daily
Other Name: GS-7977
Drug: RBV
Ribavirin (RBV) 200 mg tablet administered orally once daily
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.
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
Experimental: Cohort 3
15 participants with genotype 1 or 4 HCV infection will receive LDV/SOF once daily for 12 weeks.
Drug: LDV/SOF
Ledipasvir/sofosbuvir (LDV/SOF) 90/400 mg fixed-dose combination (FDC) tablet administered orally once daily
Other Name: Harvoni®

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01958281

Locations
United States, California
San Francisco, California, United States, 94115
United States, Florida
Miami, Florida, United States, 33134
United States, Illinois
Chicago, Illinois, United States, 60611
United States, Michigan
Detroit, Michigan, United States, 48202
United States, New York
Rochester, New York, United States, 14642
United States, Texas
San Antonio, Texas, United States, 78215
United States, Washington
Seattle, Washington, United States, 98104
New Zealand
Gratton, Auckland, New Zealand, 1142
Christchurch, New Zealand, 8011
Puerto Rico
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Gilead Study Director Gilead Sciences
  More Information

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01958281     History of Changes
Other Study ID Numbers: GS-US-334-0154
2013-002897-30 ( EudraCT Number )
Study First Received: October 6, 2013
Last Updated: August 15, 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Infection
Renal Insufficiency
Kidney Diseases
Urologic Diseases
Ribavirin
Sofosbuvir
Ledipasvir
Ledipasvir, sofosbuvir drug combination
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on September 25, 2017