GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects/Genotype 1

A Study of Response-Guided Duration of Combination Therapy With GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C .
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Also See GI-5005-02 Phase 2b Trial to Include Additional Treatment Naive IL28B T/T Subjects With Genotype 1

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Recruiting
A Study of Response-Guided Duration of Combination Therapy With GS-9190, GS-9256, Pegasys® and Copegus® in Previously Untreated Subjects With Genotype 1 Chronic Hepatitis C C. ..
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Condition:
Chronic Hepatitis C Infection
Interventions:
Drug: GS-9190; Drug: GS-9256; Biological: Pegasys®; Drug: Copegus®; Drug: GS-9190 placebo; Drug: GS-9256 placebo

This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of response-guided duration of therapy with GS-9190 and GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®). Additionally, the efficacy and safety of 24 weeks of GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) will be evaluated.


Date First Received: October 18, 2010
Last Updated: October 19, 2010
Verified by: Gilead Sciences, October 2010
Clinical Trial Phase: Phase 2 Start Date: October 2010
Overall Status: Recruiting
Estimated Enrollment: 320
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Brief Summary
Official Title: “A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating 16 and 24 Weeks of Response Guided Therapy With GS-9190, GS-9256, Ribavirin (Copegus®) and Peginterferon Alfa 2a (Pegasys®) in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0123)”


This phase 2b study will evaluate the efficacy and safety of 16 and 24 weeks of response-guided duration of therapy with GS-9190 and GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®). Additionally, the efficacy and safety of 24 weeks of GS-9256 in combination with Peginterferon Alfa-2a (Pegasys®) and Ribavirin (Copegus®) will be evaluated.

Study Type: Interventional

Study Design: Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Study Primary Completion Date: September 2012

Intervention(s) in this Clinical Trial
Drug: GS-9190
GS-9190 capsule, 20 mg BID, 16 or 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 16 or 24 weeks
Biological: Pegasys®
peginterferon alfa-2a, (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75>/= 75 kg) divided twice daily (BID), up to 48 weeks
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256
GS-9256 capsule, 150 mg BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, up to 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75>/= 75 kg) divided twice daily (BID), up to 48 weeks
Drug: GS-9190 placebo
placebo matching GS-9190 capsule BID, 24 weeks
Drug: GS-9256 placebo
placebo matching GS-9256 capsule BID, 24 weeks
Biological: Pegasys®
peginterferon alfa-2a (solution for injection) 180 µg/week, 48 weeks
Drug: Copegus®
ribavirin 200 mg tablet (weight based: 1000 mg/day <75>/= 75 kg) divided twice daily (BID), 48 weeks
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Arms, Groups and Cohorts in this Clinical Trial
Experimental: Arm 1
GS-9190 and GS-9256 in combination with Pegasys® and Copegus® for 16 or 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
Experimental: Arm 2
GS-9256 (active) and placebo matching GS-9190 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® may be continued for up to 48 weeks total duration depending on individual response to therapy
Placebo Comparator: Arm 3
Placebo matching GS-9190 and placebo matching GS-9256 in combination with Pegasys® and Copegus® for 24 weeks; Pegasys® and Copegus® will be continued for up to 48 weeks total
duration
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Outcome Measures for this Clinical Trial
Primary Measures
Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation
Time Frame: 24 weeks of off-treatment follow-up
Safety Issue?: No
Secondary Measures
Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events
Time Frame: Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up
Safety Issue?: Yes
Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256
Time Frame: Through up to 48 weeks treatment period, 24 weeks of off-treatment follow-up, and up to 48 weeks of follow-up in the Resistance Registry Substudy
Safety Issue?: No
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Viral dynamics and steady state pharmacokinetics of GS-9190 and GS-9256 when administered in combination with PEG and RBV; measured by HCV RNA levels and plasma concentrations of GS-9190 and GS-9256 over time
Time Frame: Through Week 4 of therapy
Safety Issue?: No
Long-term assessment of plasma HCV RNA in subjects who achieve SVR
Time Frame: 36 months following Week 72
Safety Issue?: No
Criteria for Participation in this Clinical Trial

Inclusion Criteria:

Adult subjects 18 to 70 years of age
Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
Monoinfection with HCV genotype 1a or 1b
HCV treatment-naïve
Body mass index (BMI) between 18 and 36 kg/m2
Creatinine clearance >/= 50 mL/min
Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
Screening laboratory values within defined thresholds for ALT, AST, leukopenia, neutropenia, anemia, thrombocytopenia, thyroid stimulating hormone (TSH), potassium, magnesium
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Exclusion Criteria:

Autoimmune disease
Decompensated liver disease or cirrhosis
Poorly controlled diabetes mellitus
Severe psychiatric illness
Severe chronic obstructive pulmonary disease (COPD)
Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
History of hemoglobinopathy
Known retinal disease
Subjects who are immunosuppressed
Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
Subjects who are on or are expected to be on a potent cytochrome P450 (CYP) 3A4 or Pgp inhibitor, or a QT prolonging medication within 2 weeks of Baseline (Day 1) or during the study
Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening
Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 70 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Clinical Trial Sponsor Information
Lead Sponsor: Gilead Sciences Industry

Overall Clinical Trial Officials and Contacts
David Oldach, MD Study Director Gilead Sciences

Overall Contact: Brage Garofalo (650) 522-4732

Additional Information
Information obtained from ClinicalTrials.gov on October 28, 2010

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT01225380

Study ID Number: GS-US-196-0123

ClinicalTrials.gov Identifier: NCT01225380

Health Authority: United States: Food and Drug Administration

Clinical Trials Authorship and Review
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