Efficacy and Safety Study of GS-9256 and GS-9190 Alone and in Combination With Ribavirin for 28 Days in Patients With Chronic Hepatitis C Virus Infection

• Status: Completed
• Trial end date: 2012-01-01
• Target enrollment: 0
• Participant gender: All

Summary

This a phase 2, randomized, open-label trial of GS-9256 plus GS-9190, two oral anti HCV drugs, for 28 days with and without ribavirin (RIBA) and with pegylated interferon (PEG)/RIBA in adults with chronic Hepatitis C virus (HCV). In Part A, approximately thirty (30) subjects 18-70 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of the two treatment groups (GS-9256 plus GS-9190 or GS-9256 plus GS-9190 plus RIBA). In Part B, an additional fifteen (15) subjects will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).

Following randomization, subjects will return for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 28 day treatment phase. During the treatment phase, subjects will receive oral study drugs twice daily for 28 days and PEG once weekly for Part B. Subjects then receive PEG/RIBA as local SOC starting on Day 28 (not provided as part of the study). Following completion of the 28-day treatment phase, subjects will be followed for approximately 72 weeks.

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

Details

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

Criteria

Inclusion Criteria:

• Adult subjects, ages 18-70

• Willing able to provide informed consent

• BMI between 18 and 36 kg/m2 (inclusive)

• Chronic HCV infection, genotype 1

• HCV RNA >/= 3 log, but < 7.2 log10 IU/ml at screen

• Liver biopsy, FibroTest, or FibroScan indicating absence of cirrhosis

• HCV treatment naïve with imminent plans to start treatment with PEG/RIBA

• QTcF
• ALT, AST, GGT < 5 X ULN at the screening visit

• Creatinine clearance >= 50 mL/min

• Absolute neutrophil count >= 1500/mm3

• Hemoglobin >/= 12 g/dL (female), >/= 13 g/dL (male)

• Males agree to use of effective contraception and refrain from sperm donation

• Able to comply with dosing instructions and study visits

• Of generally good health

Exclusion Criteria:

• Females of child-bearing potential or males with female partners who are pregnant or planning to become pregnant

• Infection with other HCV genotype or multiple HCV genotypes

• Poorly controlled diabetes

• Hemoglobinopathy or known retinal disease

• History of sarcoidosis or invasive malignancy

• Untreated or significant psychiatric illness

• Co-infection with hepatitis B virus or human immunodeficiency virus

• Chronic use of systemic immunosuppressive agents

• Autoimmune disorders

• Severe COPD

• History of significant cardiac disease

• Known cirrhosis

• Non-HCV chronic liver disease

• Transplantation

• Suspicion of hepatocellular carcinoma

• Bilirubin above the normal range or Gilbert's syndrome

• Decompensated liver disease

• Clinically significant illness

• GI disease that could interfere with absorption

• Acute porphyria

• Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males or current binge drinking

• Positive urine drug screen

• History of difficult blood collection

• Significant recent blood loss

• Prohibited medications, including H2 antagonists, investigational agents

• Restricted fruits, fruit juices

• Hypersensitivity