A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Comparing 24 or 48 Weeks of GS-9190, in Combination with Peginterferon Alfa 2a and Ribavirin, to 48 Weeks of Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV) Infection.
- Conditions
- Genotype-1 Chronic Hepatitis C Virus (HCV) InfectionMedDRA version: 9.1Level: LLTClassification code 10008912Term: Chronic hepatitis C
- Registration Number
- EUCTR2008-004527-31-DE
- Lead Sponsor
- Gilead Sciences Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 248
• Male or female aged 18 to 70 years
• 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 as calculated per protocol
• Subjects must have the following laboratory parameters: hemoglobin = 11 g/dL, platelets = 90,000/mm3, white blood cell count > 2,500 cells/ µL, neutrophils > 1500/mm3 (unless considered a physiologic variant discussed with and approved by the Gilead Medical Monitor), and TSH within normal limits (can be controlled on medications)
• Creatinine clearance (CLcr) = 50 mL/min, as calculated by the Cockcroft-Gault equation (please refer to the protocol)
• Willing and able to provide written informed consent and to comply with all study requirements
• Of generally good health as determined by the Investigator, based upon physical examination, laboratory parameters, ECG findings, vital signs, and medical history; physical examination must be inclusive of retinal exam (e.g., opthalmoscopic evaluation)
• 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 ß-human chorionic gonadotropin (hCG) at screening and negative urine ß-HCG at Baseline (Day 1) prior to the first study drug administration. Female subjects of childbearing potential and male subjects with a female partner of childbearing potential must agree that they and their partner will use effective contraception (two separate forms of contraception simultaneously, one of which must be an effective barrier method, or be nonheterosexually 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 and, in Europe, for 28 weeks after the last dose of RIBA for male subjects and their female partners of childbearing potential.
- 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 and, in Europe, for 28 weeks after the last dose of RIBA.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range
• Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
• Males who have partners who are pregnant or are planning to become pregnant
• Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
• Males who have partners who are pregnant or are planning to become pregnant
• Males and females of reproductive potential who are unwilling to use two forms of effective birth control throughout the duration of study treatment and for 24 weeks after the last dose of RIBA; in Europe (EU), this period extends to 28 weeks after the last dose of RIBA for male subjects and their female partners of childbearing potential. 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 Gilead Medical Monitor and improved glucose control is anticipated
• History of hemoglobinopathy (e.g., thalassemia)
• History of known retinal disease
• History of sarcoidosis
• 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 hepatocelluar carcinoma (e.g., a-fetoprotein > 50 ng/mL)
• Chronic liver disease of a non-HCV etiology (e.g., hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency, cholangitis)
• Decompensated liver disease defined as conjugated bilirubin > 1.5 × ULN, prothrombin time (PT) > 1.5 × ULN, serum albumin < 3.0 g/dL, or prior history of clinical hepatic decompensation (e.g., ascites, jaundice, encephalopathy, variceal hemorrhage)
• 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 (e.g., systemic lupus erythematosus, rheumatoid arthritis, psoriasis of greater than mild severity). Subjects with treated hypothyroidism with normal TSH may be enrolled.
• Severe chronic obstructive pulmonary disease (e.g., FEV1 < 1.5 L, or a daily requirement for inhaled bronchodilators or corticosteroids)
• 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 Fridericia’s formula: QTcF=QT/RR0.333
• 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 cour
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method