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

Phase 2

Completed

• Conditions: Chronic Hepatitis C Infection
• Interventions: Drug: GS-9190; Drug: GS-9190 placebo; Drug: GS-9256; Drug: GS-9256 placebo; Biological: Pegasys®; Drug: Copegus®

• Registration Number: NCT01225380
• Lead Sponsor: Gilead Sciences

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10
• Study First Submitted: 2010-10-18
• Study First Submitted QC: 2010-10-19
• Study First Posted: 2010-10-21
• Primary Completion: 2013-01
• Study Completion: 2013-09
• Disposition First Submitted: 2013-10-31
• Disposition First Submitted QC: 2013-10-31
• Disposition First Posted: 2013-11-26
• Status Verified: 2013-12
• Last Update Submitted: 2013-12-20
• Last Update Posted: 2014-01-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 324

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

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 3	Pegasys®	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
Arm 1	GS-9190	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
Arm 1	Pegasys®	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
Arm 1	Copegus®	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
Arm 2	GS-9190 placebo	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
Arm 2	GS-9256	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
Arm 2	Pegasys®	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
Arm 2	Copegus®	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
Arm 3	GS-9190 placebo	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
Arm 3	GS-9256 placebo	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
Arm 3	Copegus®	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
Arm 1	GS-9256	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

Primary Outcome Measures

Name	Time	Method
Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation	24 weeks of off-treatment follow-up

Secondary Outcome Measures

Name	Time	Method
Safety and tolerability of therapy as measured by frequency of laboratory abnormalities, reported adverse events, and discontinuations due to adverse events	Through up to 48 weeks treatment period and 24 weeks of off-treatment follow-up
Emergence of viral resistance following initiation of therapy with GS-9190 and GS-9256	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
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	Through Week 4 of therapy
Long-term assessment of plasma HCV RNA in subjects who achieve SVR	36 months following Week 72	Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.

Trial Locations

Locations (114)

Mayo Clinic; 🇺🇸 Phoenix, Arizona, United States

Advanced Clinical Research Institute; 🇺🇸 Anaheim, California, United States

Scripps Clinic; 🇺🇸 La Jolla, California, United States

Cedars-Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Medical Associates Research Group; 🇺🇸 San Diego, California, United States

Kaiser Permanente; 🇺🇸 San Diego, California, United States

California Pacific Medical Center; 🇺🇸 San Francisco, California, United States

South Denver Gastroenterology; 🇺🇸 Englewood, Colorado, United States

University of Florida; 🇺🇸 Gainesville, Florida, United States

University of Miami Center for Liver Diseases; 🇺🇸 Miami, Florida, United States

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