Safety, Tolerability, and Antiviral Activity of 24 or 48 Weeks of GS-9190 in Combination With Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection
NCT ID: NCT00743795
Last Updated: 2013-11-05
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
252 participants
INTERVENTIONAL
2008-10-31
2013-09-30
Brief Summary
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Detailed Description
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Arm 1: PEG/RIBA + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 62)
Arm 2: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 124)
Arm 3: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 62).
Randomization will be stratified by plasma HCV RNA level (\< or ≥ 400,000 IU/mL) at screening and race (of African descent or other).
In order to ensure adequate representation of subjects with genotypes 1a and 1b in this trial, enrollment for either genotype will be capped at 120 subjects. Once 120 subjects of either genotype (e.g., genotype 1a) have been randomized, subsequent enrollment will only be allowed for subjects with the other genotype (e.g., genotype 1b).
The duration of double-blind treatment is 48 weeks plus 24 weeks of treatment-free follow-up; however subjects in Arm 3 will stop all medication at Week 24 if they have achieved an RVR (defined by undetectable HCV RNA following 4 weeks on therapy) and have maintained that response thereafter. Subjects will only learn that they have been randomized to Arm 3 if, at Week 24, having achieved criteria for stopping therapy, they are instructed to stop. All other subjects will remain blinded to their treatment status throughout the course of the study.
The standard of care treatment stopping criterion used in clinical practice when treating HCV with PEG/RIBA, failure to achieve EVR, will be utilized in this trial. Additionally, subjects with detectable plasma HCV RNA at Week 24 will discontinue all study medications no later than the Week 28 visit and will be followed off-treatment for 24 weeks.
Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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1
Peginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)
placebo
oral BID
Peginterferon Alfa 2a
All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.
Ribavirin
Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.
2
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)
GS-9190
40 mg oral BID
Peginterferon Alfa 2a
All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.
Ribavirin
Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.
3
Peginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).
GS-9190
40 mg oral BID
Peginterferon Alfa 2a
All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.
Ribavirin
Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.
Interventions
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placebo
oral BID
GS-9190
40 mg oral BID
Peginterferon Alfa 2a
All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.
Ribavirin
Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Chronic HCV infection for at least 6 months prior to Baseline (Day 1) (anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator)
* Liver biopsy results within the past 2 years prior to Baseline (Day 1) indicating the absence of cirrhosis
* HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
* Mono-infection with HCV genotype 1a or 1b
* Detectable plasma HCV RNA at Screening
* BMI between 19 and 36 kg/m2
* Willing and able to provide written informed consent and to comply with all study requirements
* Of generally good health as determined by the Investigator
* Subject agrees to use adequate skin protection (e.g., sunblocking agent) when exposed to the sun.
* Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal \< 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum β-human chorionic gonadotropin (hCG) at screening and negative urine pregnancy test prior to the first study drug administration.
* All subjects (male and female) must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for 24 weeks after the last dose of RIBA.
* Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
* Female subjects who are postmenopausal for less than two years are required to have FSH \> 40 mIU/mL. If the FSH is ≤ 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study.
* Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA
Exclusion Criteria
* Males who have partners planning to become pregnant
* Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week 72. One method should include a condom with spermicide for males
* Infection with non-genotype 1 HCV
* Poorly controlled diabetes mellitus (hemoglobin A1c \> 7) unless treatment intervention has been reviewed with the Medical Monitor and improved glucose control is anticipated
* History of sarcoidosis
* History of hemoglobinopathy (e.g., thalassemia)
* History of known retinal disease
* History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen)
* Evidence of hepatocellular carcinoma
* Chronic liver disease of a non-HCV etiology
* Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
* Co-infection with HIV, HBV, or multiple HCV genotypes
* Chronic use of systemic immunosuppressive agents
* Presence of autoimmune disorders. Subjects with treated hypothyroidism with normal TSH may be enrolled.
* Severe chronic obstructive pulmonary disease
* History of clinically significant cardiac disease, including a family history of Long QT Syndrome, and/or evidence of the following ECG abnormalities at screening: QTcF (QT corrected using Fridericia's formula) of \> 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of \> 120 msec; bradycardia (\< 45 beats per minute); pathologic Q-waves (Q wave of \> 40 msec or depth of \> 0.4 to 0.5 V); arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ; ventricular pre excitation; second or third degree heart block
* Positive urine screen for amphetamines or cocaine
* Known, current heroin, morphine, or methadone use
* Ongoing alcohol abuse in the judgment of the investigator (in no case intake of more than 28 units of alcohol per week \[1 unit = ½ pint of beer, 1 glass of wine, 1 shot of spirits\])
* Receiving a known potent CYP 3A4 inhibitor within 2 weeks of study drug dosing or are expected to receive such therapy during the course of study drug dosing
* Known hypersensitivity to the study drugs, their metabolites or formulation excipients
* In the judgment of the Investigator, should not participate in the study due to potential clinical or compliance issues
18 Years
70 Years
ALL
No
Sponsors
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Gilead Sciences
INDUSTRY
Responsible Party
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Principal Investigators
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Steven Knox
Role: STUDY_CHAIR
Gilead Sciences
Locations
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Anaheim, California, United States
Los Angeles, California, United States
Newport Beach, California, United States
San Clemente, California, United States
San Diego, California, United States
San Diego, California, United States
San Francisco, California, United States
Englewood, Colorado, United States
Miami, Florida, United States
North Miami Beach, Florida, United States
Orlando, Florida, United States
Sarasota, Florida, United States
Tampa, Florida, United States
Atlanta, Georgia, United States
Decatur, Georgia, United States
Chicago, Illinois, United States
Bowling Green, Kentucky, United States
Baton Rouge, Louisiana, United States
Baltimore, Maryland, United States
Baltimore, Maryland, United States
Baltimore, Maryland, United States
Boston, Massachusetts, United States
Detroit, Michigan, United States
St Louis, Missouri, United States
Cedar Knolls, New Jersey, United States
Johnson City, New York, United States
New York, New York, United States
New York, New York, United States
New York, New York, United States
New York, New York, United States
Plainview, New York, United States
Syracuse, New York, United States
Asheville, North Carolina, United States
Durham, North Carolina, United States
High Point, North Carolina, United States
Cincinnati, Ohio, United States
Cincinnati, Ohio, United States
Tulsa, Oklahoma, United States
Philadelphia, Pennsylvania, United States
Philadelphia, Pennsylvania, United States
Germantown, Tennessee, United States
Dallas, Texas, United States
Houston, Texas, United States
San Antonio, Texas, United States
Annandale, Virginia, United States
Fairfax, Virginia, United States
Norfolk, Virginia, United States
Richmond, Virginia, United States
Brussels, , Belgium
Brussels, , Belgium
Ghent, , Belgium
Leuven, , Belgium
Liège, , Belgium
Berlin, , Germany
Cologne, , Germany
Frankfurt, , Germany
Hamburg, , Germany
Hanover, , Germany
München, , Germany
Dublin, , Ireland
Dublin, , Ireland
Dublin, , Ireland
Bialystok, , Poland
Bydgoszcz, , Poland
Chorzów, , Poland
Czeladź, , Poland
Krakow, , Poland
Warsaw, , Poland
Santurce, , Puerto Rico
Birmingham, , United Kingdom
London, , United Kingdom
London, , United Kingdom
Countries
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Other Identifiers
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GS-US-196-0103
Identifier Type: -
Identifier Source: org_study_id