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-IE
- Lead Sponsor
- Gilead Sciences Incorporated
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 200
• Male or female aged 18 to 65 years
• Chronic HCV infection (i.e., anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator),
• HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
• Mono-infection with HCV genotype 1a or 1b
• BMI between 19 and 36 kg/m2 as calculated per protocol
• Subjects must have the following laboratory parameters: hemoglobin = 11 g/dL, platelets > 100,000/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)
• FibroTest analysis and eligibility will be determined by the results of these procedures and the liver function requirements below:
Eligibility based on FibroTest results: FibroTest values indicating Stage 0 liver disease - Corresponding liver function necessary for eligibility: AST and ALT > ULN, and < 10 × ULN
Eligibility based on FibroTest results: FibroTest values indicating Stage 1, 2, or 3 liver disease - Corresponding liver function necessary for eligibility: AST and ALT < 10 × ULN
• 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
• 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 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.
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 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 Gilead Medical Monitor and improved glucose control is anticipated
• 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)
• Evidence of cirrhosis (Stage 4 fibrosis based on FibroTest [unless liver biopsy performed within the prior year indicates absence of Stage 4 disease])
• 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). 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 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
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