Efficacy and Safety Study of GS-9450 Treatment for 6 Months in Patients With Chronic Hepatitis C Virus Infection - Full Text View

Purpose

This is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, multicenter study investigating the safety, tolerability and efficacy of two oral doses of GS-9450 in adults with chronic Hepatitis C Virus (HCV). Approximately 240 subjects 18-65 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of three treatment groups (80 subjects per treatment group) as follows:GS-9450 10 mg once daily,GS-9450 40 mg once daily, or matching placebo once daily.

Following randomization, subjects will return within seven business days for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 26 week treatment phase. During the treatment phase, subjects will receive study drug once daily for 24 weeks and then taper off of study drug over the following 2 weeks by receiving study drug once every other day for one week and then every 3 days for one week. Following completion of the treatment phase, subjects will enter a 4-week off-treatment follow-up phase.

Condition	Intervention	Phase
HCV Infection	Drug: GS-9450 Drug: Placebo	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Treatment
Official Title:	A Phase 2b, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GS 9450 in Adults With Chronic Hepatitis C Virus Infection (GS-US-227-0106)

Resource links provided by NLM:

MedlinePlus related topics: Hepatitis Hepatitis A Hepatitis C

Drug Information available for: Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Gilead Sciences:

Primary Outcome Measures:

Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 . [ Time Frame: Week 24 on-treatment ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Change (absolute, percent) from baseline in the Knodell necroinflammatory score [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change (absolute, percent) from pretreatment in ALT levels [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Reporting of AEs, physical examination and clinical laboratory test findings, vital signs, and HCV RNA levels [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change from baseline in the percent of apoptotic cells (TUNEL positive) as measured by TUNEL staining of liver biopsy specimens [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
Change from baseline in percent of anti-M30 monoclonal antibody positive hepatocytes (for cytokeratin-18 neoantigen expression) as measured by immunohistochemical staining of liver biopsy specimens [ Time Frame: Week 24 ] [ Designated as safety issue: No ]

Enrollment:	307
Study Start Date:	May 2009
Estimated Study Completion Date:	June 2010
Primary Completion Date:	April 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: GS-9450 10 mg/day GS-9450 taken as one 10 mg capsule by mouth once daily	Drug: GS-9450 Taken as one capsule by mouth once daily
Experimental: GS-9450 40 mg/day GS-9450 taken as one 40 mg capsule by mouth once daily	Drug: GS-9450 Taken as one capsule by mouth once daily
Placebo Comparator: Placebo Placebo taken as one placebo capsule by mouth once daily	Drug: Placebo Taken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Adult subjects, ages 18-65
Chronic HCV infection, defined as having documented HCV infection (antibody or RNA positivity) at least 6 months prior to Baseline (Day 1) with HCV viremia at screening
Screening Knodell necroinflammatory score >= 3 based on liver biopsy evaluation (as determined by local pathologist) conducted anytime during the 45-day screening period
ALT > ULN but < 10 X ULN at the screening visit
Previously failed pegylated interferon-based HCV therapy in combination with ribavirin therapy, or is unable to tolerate or has contraindications to receiving interferon or ribavirin therapy
BMI between 19 and 36 kg/m2 (inclusive)
Creatinine clearance >= 70 mL/min
absolute neutrophil count >= 1000/mm3
Hemoglobin > 10 g/dL
Have no clinical or laboratory evidence of hepatic decompensation

Exclusion Criteria:

Decompensated liver disease
Child-Pugh grade B or C cirrhosis
Evidence of hepatocellular carcinoma
Positive urine drug screen for cocaine or amphetamines
Infection with HCV genotype 3
Co-infection with hepatitis B virus or human immunodeficiency virus
Pancreatitis
Recent significant infection or symptoms of infection
Autoimmune disorders
Any history of seizure
Is a public transportation operator (pilot of airplane or ship; air traffic controller; bus, train or subway driver) or operates heavy construction machinery
Transplantation
History of malignancy
Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males
History of or current binge drinking

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874796

Show 73 Study Locations

Sponsors and Collaborators

Gilead Sciences

Investigators

Study Director:

Ken Hirsch, MD

Gilead Sciences

More Information

No publications provided

Responsible Party:	Ken Hirsch, Gilead Sciences, Inc.
ClinicalTrials.gov Identifier:	NCT00874796 History of Changes
Other Study ID Numbers:	GS-US-227-0106
Study First Received:	April 2, 2009
Last Updated:	April 27, 2010
Health Authority:	United States: Food and Drug Administration Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Gilead Sciences:

apoptosis
liver inflammation
hepatitis C

Additional relevant MeSH terms:

Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases

Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on May 23, 2013