Clinical trial NCT01435226: GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection
Official title: A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared With GS-5885, GS-9451 With Tegobuvir or RBV in Treatment-Experienced Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hepatitis C, Chronic
Keywords: Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy
Tegobuvir
Treatment Experienced
HCV RNA
Polymerase inhibitor
Protease inhibitor
Interferon intolerant
Interferon ineligible
GS-9190
GS-9451
GS-5885
Chronic Genotype 1a or 1b
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-09-16
Enrollment: 170
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.


Eligibility criteria: Inclusion Criteria:

* Age ≥18 years with chronic HCV infection
* Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
* Monoinfection with HCV genotype (GT) 1a or 1b
* HCV RNA ≥ 104 IU/mL at screening
* Prior treatment and adherence with one course of pegylated interferon alfa and RBV
* The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
* Body mass index (BMI) 18-40 kg/m2 inclusive
* Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)

  ≤ 450 msec for males and ≤ 470 msec for females.
* Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.

Exclusion Criteria:

* Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
* History of significant cardiac disease
* Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
* Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
* Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

Primary outcomes:
measure: Safety and Tolerability
timeFrame: 24 weeks
measure: Antiviral Activity
timeFrame: 24 weeks
Secondary outcomes:
measure: Viral Dynamics
timeFrame: 10 days
measure: Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics
timeFrame: predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose
measure: Antiviral Efficacy
timeFrame: 24-48 weeks
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona
state: Arizona
city: Anaheim
country: United States
facility: Advanced Clinical Research Institute, LLC
state: California
city: Beverly Hills
country: United States
facility: California Liver Institute
state: California
city: Coronado
country: United States
facility: SCTI Research Foundation Liver Center
state: California
city: La Jolla
country: United States
facility: University of California, San Diego
state: California
city: Los Angeles
country: United States
facility: Lightsource Medical
state: California
city: San Diego
country: United States
facility: Medical Associates Research Group, Inc.
state: California
city: San Diego
country: United States
facility: Kaiser Permanente
state: California
city: San Francisco
country: United States
facility: California Pacific Medical Center
state: California
city: San Jose
country: United States
facility: San Jose Gastroenterology
state: California
city: Washington
country: United States
facility: Whitman Walker Clinic
state: District of Columbia
city: DeLand
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Miami
country: United States
facility: University of Miami, Center for Liver Diseases
state: Florida
city: Decatur
country: United States
facility: Infectious Disease Specialists of Atlanta
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Baltimore
country: United States
facility: Mercy Medical Center
state: Maryland
city: Lutherville
country: United States
facility: Johns Hopkins University
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Novi
country: United States
facility: Henry Ford Health System
state: Michigan
city: Bronx
country: United States
facility: Montefiore Medical Center
state: New York
city: New York
country: United States
facility: Weill Medical College of Cornell Univeristy
state: New York
city: New York
country: United States
facility: Mount Sinai School of Medicine
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Providence
country: United States
facility: University Gastroenterology
state: Rhode Island
city: Germantown
country: United States
facility: Gastro One
state: Tennessee
city: Dallas
country: United States
facility: Southwest Infectious Disease Clinical Research, Inc
state: Texas
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
city: Houston
country: United States
facility: Therapeutic Concepts, PA
state: Texas
city: Houston
country: United States
facility: The University of Texas Health Sciences Center at Houston
state: Texas
city: San Antonio
country: United States
facility: Alamo Medical Research, Ltd.
state: Texas
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
city: Newport News
country: United States
facility: Bon Secours St. Mary's Hospital of Richmond, Inc.
state: Virginia
city: Norfolk
country: United States
facility: Digestive and Liver Disease Specialists
state: Virginia
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
city: Madison
country: United States
facility: University of Wisconsin Hospital and Clinics
state: Wisconsin
city: Berlin
country: Germany
facility: Leber- and Studienzentrum am Checkpoint
city: Berlin
country: Germany
facility: Charite - Universitatsmedizin Berlin Campus Virchow-Klinikum
city: Bonn
country: Germany
facility: Universitätsklinikum Bonn
city: Düsseldorf
country: Germany
facility: Center for HIV and Hepatogastroenterology
city: Frankfurt
country: Germany
facility: Klinikum der Johann Wolfgang Goethe Universitaet
city: Freiburg
country: Germany
facility: Medizinische Universitatsklinik
city: Hamburg
country: Germany
facility: Universitatsklinikum Hamburg-Eppendorf
city: Hannover
country: Germany
facility: Medizinische Hochschule Hannover
city: Heidelberg
country: Germany
facility: Klinikum der Universität Heidelberg
city: Kiel
country: Germany
facility: Gastroenterologisch-Hepatologisches Zentrum Kiel
city: Leipzig
country: Germany
facility: Universitätsklinikum Leipzig
city: Mainz
country: Germany
facility: Johannes Gutenberg University Hospital
city: Muenchen
country: Germany
facility: Klinikum Innenstadt der LMU Munchen
city: Würzburg
country: Germany
facility: Universitätsklinikum Würzburg - Med Klinik und Poliklinik
Study officials:
affiliation: Gilead Sciences
name: John McNally, PhD
role: STUDY_DIRECTOR
References: