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

• Status: Completed
• Trial end date: 2013-09-01
• Target enrollment: 0
• Participant gender: All

Summary

The purpose of this study is to compare the safety, tolerability and effectiveness of the experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and ribavirin for the treatment of genotype-1 chronic hepatitis C infection.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Gilead Sciences
• Treatments: Interferon-alpha; Peginterferon alfa-2a; Ribavirin

Criteria

Inclusion Criteria:

• Adult subjects (18 - 70 years of age)

• 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:

• 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 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