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 - Full Text View

Sponsor:	Gilead Sciences
Information provided by:	Gilead Sciences
ClinicalTrials.gov Identifier:	NCT01072695

Purpose

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.

Condition	Intervention	Phase
HCV Infection	Drug: GS-9256 Drug: GS-9190 Drug: Ribavirin Drug: Peginterferon alfa-2a	Phase II

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Phase 2, Randomized, Open-Label Trial of GS-9256 Plus GS-9190 Alone and in Combination With Ribavirin for 28 Days in Treatment Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection (Protocol No. GS-US-196-0112)

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:

Percentage of subjects achieving rapid virologic response (RVR) [ Time Frame: Day 28 ] [ Designated as safety issue: No ]
AEs, physical examination and clinical laboratory test findings, vital signs, ECGs [ Time Frame: Throughout first six weeks of study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Plasma pharmacokinetics [ Time Frame: Throughout Day 28 ] [ Designated as safety issue: No ]
Viral resistance [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	45
Study Start Date:	February 2010
Estimated Study Completion Date:	February 2012
Primary Completion Date:	October 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Arm 1	Drug: GS-9256 75 mg BID x 28 days Drug: GS-9190 40 mg BID x 28 days
Experimental: Arm 2	Drug: GS-9256 75 mg BID x 28 days Drug: GS-9190 40 mg BID x 28 days Drug: Ribavirin 1000-1200 mg/day given BID Other Name: COPEGUS
Experimental: Arm 3	Drug: GS-9256 75 mg BID x 28 days Drug: GS-9190 40 mg BID x 28 days Drug: Ribavirin 1000-1200 mg/day given BID Other Name: COPEGUS Drug: Peginterferon alfa-2a 180 ug q week Other Name: Pegasys

Detailed Description:

GS-9256 (an HCV NS3 protease inhibitor) plus GS-9190 (non-nucleoside HCV NS5B inhibitor) will be administered for 28 days with and without RIBA (weight-based dosing) and with PEG/RIBA in treatment-naïve subjects with chronic genotype 1 HCV infection. In Part A, thirty (30) subjects with genotype 1 will be randomized to 75 mg GS-9256 BID plus 40 mg GS-9190 BID or 75 mg GS-9256 BID plus 40 mg GS-9190 BID plus RIBA 1000-1200 mg/day for 28 days. In Part B, an additional fifteen (15) subjects with genotype 1 will receive 75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA for 28 days. After the 28-day treatment period, subjects will receive PEG/RIBA as standard of care (SOC).

In Part A, for any subjects meeting pre-defined, individual, virologic criteria, PEG/RIBA standard of care will be started prior to Day 28.

Both PEG and RIBA will be administered at their currently approved dosages for treatment of HCV infection in accordance with appropriate labeling. Subjects will be monitored for safety (including ECG monitoring), antiviral activity, pharmacokinetics, and resistance 2-3 times weekly through Day 28.

Eligibility

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

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 </= 450 msec at screen
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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT01072695

Locations

Belgium

Brussels, Belgium, 1200

Bruxelles, Belgium, 1070
France

Clichy, France, 92110

La Tronche, France, 38700

Paris, France, 75475
Germany

Duesseldorf, Germany, 40237

Frankfurt, Germany, 60590

Hamburg, Germany, 20099

Hannover, Germany, 30625

Wurzburg, Germany, 97080
United Kingdom

London, United Kingdom, E1 2AT

London, United Kingdom, SE5 9RS

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Juan Betular

Gilead Sciences

More Information

No publications provided

Responsible Party:	Steven Knox, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier:	NCT01072695 History of Changes
Other Study ID Numbers:	GS-US-196-0112
Study First Received:	February 19, 2010
Last Updated:	May 10, 2011
Health Authority:	Germany: Federal Institute for Drugs and Medical Devices; France: Afssaps - French Health Products Safety Agency; Belgium: Federal Agency for Medicinal Products and Health Products; United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Gilead Sciences:

Hepatitis C
HCV
GS-9256
GS-9190
Genotype 1

Additional relevant MeSH terms:

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

Hepatitis, Chronic
Ribavirin
Peginterferon alfa-2a
Interferon-alpha
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 09, 2012