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

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT00874796

Collaborator

(none)

307

Enrollment

Locations

Arms

Duration (Months)

4.2

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

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 or Disease	Intervention/Treatment	Phase
HCV Infection	Drug: GS-9450 Drug: Placebo	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

307 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, 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)

Study Start Date :

May 1, 2009

Actual Primary Completion Date :

Apr 1, 2010

Actual Study Completion Date :

Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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

Arm

Intervention/Treatment

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

Outcome Measures

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 . [Week 24 on-treatment]

Secondary Outcome Measures

Change (absolute, percent) from baseline in the Knodell necroinflammatory score [Baseline to Week 24]
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels [Baseline to Week 24]
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities [Up to 24 weeks plus 30 days following the last dose of study drug]
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels [Baseline to Week 24]
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens [Baseline to Week 24]
Change from baseline in the percent of apoptotic cells [Baseline to Week 24]
Change from baseline in the percent of apoptotic cells (transferase deoxyuridine triphosphate [dUTP] nick end labeling [TUNEL] positive) as measured by TUNEL staining of liver biopsy specimens
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes [Baseline to Week 24]
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
Change From Baseline in HCV RNA [Baseline to to Week 24]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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 > the upper limit of the normal range (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

Locations

	City	State	Country
1	Phoenix	Arizona	United States
2	Tucson	Arizona	United States
3	Anaheim	California	United States
4	Beverly Hills	California	United States
5	Cypress	California	United States
6	La Jolla	California	United States
7	Mission Hills	California	United States
8	Palm Springs	California	United States
9	Pasadena	California	United States
10	San Clemente	California	United States
11	San Diego	California	United States
12	Washington	District of Columbia	United States
13	Hialeah	Florida	United States
14	Miami	Florida	United States
15	North Miami Beach	Florida	United States
16	Orlando	Florida	United States
17	Sarasota	Florida	United States
18	Tampa	Florida	United States
19	Decatur	Georgia	United States
20	Chicago	Illinois	United States
21	Indianapolis	Indiana	United States
22	Louisville	Kentucky	United States
23	Baton Rouge	Louisiana	United States
24	New Orleans	Louisiana	United States
25	Annapolis	Maryland	United States
26	Baltimore	Maryland	United States
27	Boston	Massachusetts	United States
28	Novi	Michigan	United States
29	St. Louis	Michigan	United States
30	Plymouth	Minnesota	United States
31	Omaha	Nebraska	United States
32	Las Vegas	Nevada	United States
33	Hillsborough	New Jersey	United States
34	Morristown	New Jersey	United States
35	Santa Fe	New Mexico	United States
36	Johnson City	New York	United States
37	New York	New York	United States
38	Plainview	New York	United States
39	Cincinnati	Ohio	United States
40	Cleveland	Ohio	United States
41	Philadelphia	Pennsylvania	United States
42	Providence	Rhode Island	United States
43	Chattanooga	Tennessee	United States
44	Germantown	Tennessee	United States
45	Dallas	Texas	United States
46	San Antonio	Texas	United States
47	Fairfax	Virginia	United States
48	Falls Church	Virginia	United States
49	Norfolk	Virginia	United States
50	Seattle	Washington	United States
51	Madison	Wisconsin	United States
52	Vancouver	British Columbia	Canada
53	Winnipeg	Manitoba	Canada
54	London	Ontario	Canada
55	Berlin		Germany
56	Bonn		Germany
57	Essen		Germany
58	Frankfurt am Main		Germany
59	Hamburg		Germany
60	Hannover		Germany
61	Köln		Germany
62	Mainz		Germany
63	Bialystok		Poland
64	Bydgoszcz		Poland
65	Chorzów		Poland
66	Kielce		Poland
67	Wroclaw		Poland
68	San Juan		Puerto Rico
69	Santurce		Puerto Rico
70	Brighton		United Kingdom
71	London		United Kingdom
72	Nottingham		United Kingdom
73	Sheffield		United Kingdom