GS-5885 Alone or in Combination With GS-9451 With Peginterferon Alfa 2a and Ribavirin in Treatment Chronic Genotype 1 Hepatitis C Virus

Phase 2

Completed

• Conditions: Hepatitis C, Chronic
• Interventions: Drug: GS-5885; Drug: GS-9451; Biological: peginterferon alfa-2a; Drug: ribavirin tablet; Drug: GS-9451 Placebo

• Registration Number: NCT01356160
• Lead Sponsor: Gilead Sciences

Brief Summary

This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy with GS-5885 Alone or in Combination with GS-9451 with Peginterferon Alfa 2a and Ribavirin in Treatment Naïve Subjects with Chronic Genotype 1 Hepatitis C Virus Infection.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2011-05-02
• Study First Submitted QC: 2011-05-18
• Study First Posted: 2011-05-19
• Study Start: 2011-07
• Primary Completion: 2013-06
• Study Completion: 2013-06
• Disposition First Submitted: 2013-11-26
• Disposition First Submitted QC: 2013-11-26
• Disposition First Posted: 2013-12-20
• Status Verified: 2014-01
• Last Update Submitted: 2014-01-02
• Last Update Posted: 2014-02-03

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 351

Inclusion Criteria

• Males and females 18-70 years of age
• Chronic HCV infection
• Subjects must have liver biopsy results (≤ 2 years prior to Screening) indicating the absence of cirrhosis.
• Monoinfection with HCV genotype 1
• HCV RNA > 10^4 IU/mL at Screening
• HCV treatment naïve
• Candidate for PEG/RBV therapy
• Body mass index (BMI) 18-36 kg/m2, inclusive
• Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline.

Exclusion Criteria

• Pregnant female or male with pregnant female partner
• Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH)
• Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
• Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Patients on stable methadone or buprenorphine maintenance treatment for at least 6 months prior to Screening may be included into the study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1	peginterferon alfa-2a	RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV
Arm 1	ribavirin tablet	RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV
Arm 2	GS-5885	RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV
Arm 2	peginterferon alfa-2a	RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV
Arm 2	ribavirin tablet	RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV
Arm 2	GS-9451 Placebo	RGT with GS-5885 30 mg QD + GS-9451 placebo QD + PEG/RBV
Arm 1	GS-5885	RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV
Arm 1	GS-9451	RGT with GS-5885 30 mg QD + GS-9451 200 mg QD + PEG/RBV

Primary Outcome Measures

Name	Time	Method
To evaluate the antiviral efficacy of response guided therapy.	Through 24 weeks post-treatment	To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as plasma HCV RNA \< Lower Limit of Quantification (LLoQ) at 24 weeks post-treatment) of response guided therapy (RGT) with GS-5885 + GS-9451 + PEG/RBV, or GS-5885 + PEG/RBV.

Secondary Outcome Measures

Name	Time	Method
To evaluate the safety and tolerability of each regimen.	Through 24 weeks post-treatment	The primary safety endpoint is any AE leading to permanent discontinuation of study drugs.
To characterize viral dynamics of GS-5885 and GS-9451 when administered with PEG and RBV.	Through Day 10 on study	HCV RNA levels, pharmacokinetics and viral sequencing
To characterize the viral resistance to GS-5885 and GS-9451 when administered in combination with PEG and RBV.	12 or 24 weeks	Plasma samples will be collected and stored at each visit for possible resistance analysis.
To characterize steady state pharmacokinetics of GS-5885 and GS-9451 when administered with PEG and RBV.	Through 48 weeks of treatment	Plasma concentrations of the study drug over time will be summarized using descriptive statistics.