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 - Full Text View

Purpose

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.

Condition	Intervention	Phase
Chronic Hepatitis C Infection	Drug: GS-9190 Drug: GS-9256 Biological: Pegasys® Drug: Copegus® Drug: GS-9190 placebo Drug: GS-9256 placebo	Phase 2

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

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Ribavirin Peginterferon Alfa-2a Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Sustained virologic response (SVR) defined as undetectable HCV RNA 24 weeks after treatment cessation [ Time Frame: 24 weeks of off-treatment follow-up ] [ Designated as safety issue: No ]

Secondary Outcome 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 ] [ Designated as 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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Long-term assessment of plasma HCV RNA in subjects who achieve SVR [ Time Frame: 36 months following Week 72 ] [ Designated as safety issue: No ]
Plasma HCV RNA will be measured at approximately 6, 12, 24, and 36 months after Week 72.

Estimated Enrollment:	320
Study Start Date:	October 2010
Estimated Study Completion Date:	January 2017
Primary Completion Date:	January 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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	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 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
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	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 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), up to 48 weeks
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	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 kg; 1200 mg/day >/= 75 kg) divided twice daily (BID), 48 weeks

Eligibility

Ages Eligible for Study:	18 Years to 70 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01225380

Show 114 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Bittoo Kanwar

Gilead Sciences

More Information

No publications provided

Responsible Party:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01225380 History of Changes
Other Study ID Numbers:	GS-US-196-0123
Study First Received:	October 18, 2010
Last Updated:	March 1, 2013
Health Authority:	United States: Food and Drug Administration

Keywords provided by Gilead Sciences:

Hepatitis C
HCV
Rapid Virologic Response
Sustained Virologic Response
Direct Acting Antiviral
Combination Therapy

HCV RNA
Polymerase inhibitor
Protease inhibitor
Treatment naïve
GS-9190
GS-9256

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections

RNA Virus Infections
Flaviviridae Infections
Ribavirin
Peginterferon alfa-2a
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 21, 2013