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Trial record 4 of 11 for:    GS-9451 OR Vedroprevir

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

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ClinicalTrials.gov Identifier: NCT01371578
Recruitment Status : Completed
First Posted : June 13, 2011
Last Update Posted : February 11, 2014
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Hepatitis C, Chronic Drug: GS-5885 tablet Drug: GS-9451 tablet Biological: peginterferon alfa-2a Drug: ribavirin tablet Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 163 participants
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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 Infection (Protocol GS US 256 0124)
Study Start Date : July 2011
Actual Primary Completion Date : March 2013
Actual Study Completion Date : March 2013

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Arm 2

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.

Drug: GS-5885 tablet
30 mg active tablet

Drug: GS-9451 tablet
two active 100 mg tablets

Biological: peginterferon alfa-2a
peginterferon alfa-2a (solution for injection) 180 µg/week

Drug: ribavirin tablet
ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); tablet




Primary Outcome Measures :
  1. Sustained Virologic Response (SVR) [ Time Frame: 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 :
  1. Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks [ Time Frame: 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.

  2. Safety and Tolerability [ Time Frame: 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.

  3. Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV [ Time Frame: Through Week 2 of therapy ]
    HCV RNA levels, pharmacokinetics, and viral sequencing

  4. Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV [ Time Frame: 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).

  5. Emergence of Viral Resistance [ Time Frame: 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.



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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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
  • Creatinine clearance ≥ 50 mL/min.
  • 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

Exclusion Criteria:

  • 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01371578


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Locations
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United States, Alabama
Digestive Health Specialists of the Southeast
Dothan, Alabama, United States, 36305
Alabama Liver and Digestive Specialists
Montgomery, Alabama, United States, 36116
United States, California
California Liver Institute
Beverly Hills, California, United States, 90211
Scripps Clinic
La Jolla, California, United States, 92037
University of California Davis Medical Center
Sacramento, California, United States, 95817
RESEARCH and EDUCATION, INC
San Diego, California, United States, 92015
Medical Associates Research Group
San Diego, California, United States, 92123
Kaiser Permanente
San Diego, California, United States, 92154
United States, Colorado
University of Colorado Denver
Aurora, Colorado, United States, 80045
South Denver Gastroenterology
Englewood, Colorado, United States, 80110
United States, Florida
Bach and Godofsky Infectious Diseases
Bradenton, Florida, United States, 34209
University of Florida
Gainesville, Florida, United States, 32610
University of Miami
Miami, Florida, United States, 33136
Orlando Immunology Center
Orlando, Florida, United States, 32803
South Florida Center of Gastroenterology, LLC
Wellington, Florida, United States, 33414
United States, Georgia
Emory University, Infectious Disease Clinic
Atlanta, Georgia, United States, 30308
Digestive Healthcare of Georgia
Atlanta, Georgia, United States, 30309
Dekalb Gastroenterology
Decatur, Georgia, United States, 30033
Gastrointestinal Specialists of Georgia PC
Marietta, Georgia, United States, 30060
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
Indianapolis Gastroenterology Research Foundation
Indianapolis, Indiana, United States, 46237
United States, Kentucky
Graves Gilbert Clinic
Bowling Green, Kentucky, United States, 42101
United States, Louisiana
Gastroenterology Associates, LLC
Baton Rouge, Louisiana, United States, 70809
United States, Maryland
Digestive Disease Associates, PA
Baltimore, Maryland, United States, 21229
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02115
Partners in Internal Medicine, P.C.
Worcester, Massachusetts, United States, 01608
United States, Michigan
Henry Ford Health System
Detroit, Michigan, United States, 48202
United States, Mississippi
Gastrointestinal Associates, PA
Jackson, Mississippi, United States, 39202
Digestive Health Specialists, PA
Tupelo, Mississippi, United States, 38801
United States, New Jersey
ID Care 105
Hillsborough, New Jersey, United States, 08844
Atlantic Research Affiliates, LLC
Morristown, New Jersey, United States, 07960
United States, New Mexico
Southwest CARE Center
Santa Fe, New Mexico, United States, 87505
United States, New York
Binghamton Gastroenterology
Binghamton, New York, United States, 13903
North Shore University Hospital
Manhasset, New York, United States, 11030
Concorde Medical Group
New York, New York, United States, 10016
Cornell University Gastroenterology & Hepatology
New York, New York, United States, 10021
United States, North Carolina
Asheville Gastroenterology Associates, P.A.
Asheville, North Carolina, United States, 28801
Duke University Medical Center
Durham, North Carolina, United States, 27710
Cumberland Research Associates, LLC
Fayetteville, North Carolina, United States, 28304
United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45267
United States, Oklahoma
Options Health Research, LLC
Tulsa, Oklahoma, United States, 74104
United States, Rhode Island
University Gastroenterology
Providence, Rhode Island, United States, 02905
United States, Tennessee
Memphis Gastroenterology Group
Germantown, Tennessee, United States, 38138
Columbia Medical Group, The Frist Clinic
Nashville, Tennessee, United States, 37203
Nashville Medical Research Institute
Nashville, Tennessee, United States, 37205
Nashville Gastrointestinal Specialists, Inc
Nashville, Tennessee, United States, 37211
United States, Texas
The North Texas Research Institute
Arlington, Texas, United States, 76012
Baylor University Medical Center
Dallas, Texas, United States, 75246
Kelsey Research Foundation
Houston, Texas, United States, 77005
Research Specialists of Texas
Houston, Texas, United States, 77030
United States, Virginia
Metropolitan Research
Fairfax, Virginia, United States, 22031
Digestive and Liver Disease Specialists
Norfolk, Virginia, United States, 23502
Liver Institute of Virginia
Richmond, Virginia, United States, 23249
United States, Washington
Virginia Mason Medical Center, Digestive Disease Institute
Seattle, Washington, United States, 98101
Puerto Rico
Fundacion de Investigacion de Diego
San Juan, Puerto Rico, 00927
Sponsors and Collaborators
Gilead Sciences
Investigators
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Study Chair: Bittoo Kanwar, MD Gilead Sciences

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Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT01371578     History of Changes
Other Study ID Numbers: GS-US-256-0124
First Posted: June 13, 2011    Key Record Dates
Last Update Posted: February 11, 2014
Last Verified: January 2014

Keywords provided by Gilead Sciences:
GS-9451
Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-5885
GS-9190
Tegobuvir

Additional relevant MeSH terms:
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Hepatitis A
Hepatitis C
Hepatitis C, Chronic
Hepatitis
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections
Hepatitis, Chronic
Ribavirin
Antiviral Agents
Peginterferon alfa-2a
Interferon-alpha
Ledipasvir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs