Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection
- Conditions
- Hepatitis C, Chronic
- Interventions
- Registration Number
- NCT01371578
- Lead Sponsor
- Gilead Sciences
- Brief Summary
This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.
- Detailed Description
In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.
In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.
As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.
All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 163
-
Male or female, aged from 18 to 70 years old, inclusive
-
Chronic HCV infection for at least 6 months prior to Baseline
-
Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
-
Monoinfection with HCV genotype 1
-
HCV RNA > 10^4 IU/mL at Screening
-
Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) 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
- Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had < 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
- Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
-
No prior treatment with an oral HCV antiviral (exclusive of RBV).
-
Body mass index (BMI) 18-36 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
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Creatinine clearance ≥ 50 mL/min.
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Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline
- Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
- Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, 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), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
- Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
- Receiving any of the prohibited concomitant medications.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 2 GS-5885 tablet AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food. PM Dosing: RBV with food. PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences. Arm 2 GS-9451 tablet AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food. PM Dosing: RBV with food. PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences. Arm 2 peginterferon alfa-2a AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food. PM Dosing: RBV with food. PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences. Arm 2 ribavirin tablet AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food. PM Dosing: RBV with food. PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences.
- Primary Outcome Measures
Name Time Method Sustained Virologic Response (SVR) through 24 weeks of off-treatment follow-up To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.
- Secondary Outcome Measures
Name Time Method Emergence of Viral Resistance through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.
Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.
Safety and Tolerability through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG \& RBV administered for 24 or 48 weeks. Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.
Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV Through Week 2 of therapy HCV RNA levels, pharmacokinetics, and viral sequencing
Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV Through Week 2 of therapy Plasma concentrations of the study drug over time will be summarized using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).
Trial Locations
- Locations (55)
Digestive Healthcare of Georgia
🇺🇸Atlanta, Georgia, United States
University of Miami
🇺🇸Miami, Florida, United States
Virginia Mason Medical Center, Digestive Disease Institute
🇺🇸Seattle, Washington, United States
Indiana University
🇺🇸Indianapolis, Indiana, United States
Beth Israel Deaconess Medical Center
🇺🇸Boston, Massachusetts, United States
Kelsey Research Foundation
🇺🇸Houston, Texas, United States
Research Specialists of Texas
🇺🇸Houston, Texas, United States
Digestive Health Specialists of the Southeast
🇺🇸Dothan, Alabama, United States
Emory University, Infectious Disease Clinic
🇺🇸Atlanta, Georgia, United States
Dekalb Gastroenterology
🇺🇸Decatur, Georgia, United States
California Liver Institute
🇺🇸Beverly Hills, California, United States
Digestive Disease Associates, PA
🇺🇸Baltimore, Maryland, United States
Bach and Godofsky Infectious Diseases
🇺🇸Bradenton, Florida, United States
Digestive Health Specialists, PA
🇺🇸Tupelo, Mississippi, United States
South Florida Center of Gastroenterology, LLC
🇺🇸Wellington, Florida, United States
Asheville Gastroenterology Associates, P.A.
🇺🇸Asheville, North Carolina, United States
Southwest CARE Center
🇺🇸Santa Fe, New Mexico, United States
Cornell University Gastroenterology & Hepatology
🇺🇸New York, New York, United States
Metropolitan Research
🇺🇸Fairfax, Virginia, United States
Concorde Medical Group
🇺🇸New York, New York, United States
RESEARCH and EDUCATION, INC
🇺🇸San Diego, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
University of Cincinnati
🇺🇸Cincinnati, Ohio, United States
Columbia Medical Group, The Frist Clinic
🇺🇸Nashville, Tennessee, United States
Nashville Medical Research Institute
🇺🇸Nashville, Tennessee, United States
Kaiser Permanente
🇺🇸San Diego, California, United States
Duke University Medical Center
🇺🇸Durham, North Carolina, United States
Nashville Gastrointestinal Specialists, Inc
🇺🇸Nashville, Tennessee, United States
Medical Associates Research Group
🇺🇸San Diego, California, United States
South Denver Gastroenterology
🇺🇸Englewood, Colorado, United States
Gastrointestinal Specialists of Georgia PC
🇺🇸Marietta, Georgia, United States
Indianapolis Gastroenterology Research Foundation
🇺🇸Indianapolis, Indiana, United States
Gastrointestinal Associates, PA
🇺🇸Jackson, Mississippi, United States
North Shore University Hospital
🇺🇸Manhasset, New York, United States
Options Health Research, LLC
🇺🇸Tulsa, Oklahoma, United States
University Gastroenterology
🇺🇸Providence, Rhode Island, United States
Memphis Gastroenterology Group
🇺🇸Germantown, Tennessee, United States
Baylor University Medical Center
🇺🇸Dallas, Texas, United States
Liver Institute of Virginia
🇺🇸Richmond, Virginia, United States
Digestive and Liver Disease Specialists
🇺🇸Norfolk, Virginia, United States
Gastroenterology Associates, LLC
🇺🇸Baton Rouge, Louisiana, United States
Scripps Clinic
🇺🇸La Jolla, California, United States
Graves Gilbert Clinic
🇺🇸Bowling Green, Kentucky, United States
Partners in Internal Medicine, P.C.
🇺🇸Worcester, Massachusetts, United States
Cumberland Research Associates, LLC
🇺🇸Fayetteville, North Carolina, United States
ID Care 105
🇺🇸Hillsborough, New Jersey, United States
Atlantic Research Affiliates, LLC
🇺🇸Morristown, New Jersey, United States
Binghamton Gastroenterology
🇺🇸Binghamton, New York, United States
The North Texas Research Institute
🇺🇸Arlington, Texas, United States
University of Florida
🇺🇸Gainesville, Florida, United States
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico
University of Colorado Denver
🇺🇸Aurora, Colorado, United States
Orlando Immunology Center
🇺🇸Orlando, Florida, United States
University of California Davis Medical Center
🇺🇸Sacramento, California, United States
Alabama Liver and Digestive Specialists
🇺🇸Montgomery, Alabama, United States