GS-5885, GS-9451 With Peginterferon Alfa 2a (PEG) and Ribavirin in Treatment-Naïve Subjects With Chronic Genotype 1 Hep C Virus Infection and IL28B CC Genotype

Sponsor

Gilead Sciences (Industry)

Overall Status

Terminated

CT.gov ID

NCT01384383

Collaborator

(none)

248

Enrollment

Locations

Arms

Duration (Months)

4.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2, randomized, open-label exploratory study that will examine the antiviral efficacy, safety, and tolerability of Response guided treatment (RGT) with GS-5885 + GS-9451

PEG/RBV (6 or 12 weeks), or Peginterferon Alfa 2a (PEG)/Ribavirin (RBV)alone (24 weeks) in treatment naïve subjects with chronic Hep C (HCV) infection with genotype (GT) 1 and IL28B CC genotype.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C	Drug: GS-5885 Drug: GS-9451 Drug: RBV Drug: PEG	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

248 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Randomized, Open-Label, Exploratory Trial of GS-5885, GS-9451 With Peginterferon Alfa 2a and Ribavirin (RBV) in Treatment-Naïve Subjects With Chronic Genotype 1 Hepatitis C Virus Infection and IL28B CC Genotype

Study Start Date :

Aug 1, 2011

Actual Primary Completion Date :

Jun 1, 2013

Actual Study Completion Date :

Jun 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.	Drug: GS-5885 GS-5885 30 mg tablet administered orally once daily Drug: GS-9451 GS-9451 200 mg tablet administered orally once daily Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
Experimental: Arm 2 Response-Guided Therapy with PEG and RBV for 24 weeks.	Drug: RBV Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg) Drug: PEG Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection

Arm

Intervention/Treatment

Experimental: Arm 1

Response-Guided Therapy with GS-5885 30 mg plus GS-9451 200 mg, plus PEG and RBV for 6 or 12 weeks.

Drug: GS-5885

GS-5885 30 mg tablet administered orally once daily

Drug: GS-9451

GS-9451 200 mg tablet administered orally once daily

Drug: RBV

Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)

Drug: PEG

Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection

Experimental: Arm 2

Response-Guided Therapy with PEG and RBV for 24 weeks.

Drug: RBV

Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)

Drug: PEG

Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection

Outcome Measures

Primary Outcome Measures

Sustained virologic response (SVR) [30 , 36 or 48 weeks]
Sustained virologic response (SVR, defined as plasma HCV RNA < lower limit of quantification [LLoQ] at 24 weeks after treatment cessation) following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 or 12 weeks, or PEG/RBV for 24 weeks in IL28B CC subjects.

Secondary Outcome Measures

Safety and tolerability of therapy [Up to 48 weeks]
Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events.
Virologic response [Weeks 2, 4, 6, 8, 10, and 12]
Virologic response at Weeks 2, 4, 6, 8, 10, and 12 (depending on treatment arm) as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse
Compare SVR [Weeks 30 and 36]
Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks.
Viral resistance [Up to 96 Weeks]
Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Males and females 18-70 years of age
Chronic HCV infection
Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis. Alternatively a non-invasive alternative to liver biopsy (such as FibroTest, FibroScan, or Acoustic Radiation Force Impulse imaging) within 6 months of Screening in countries where allowed
Monoinfection with HCV genotype 1a or 1b
HCV RNA > 10^4 IU/mL at Screening
IL28B CC genotype
HCV treatment naïve
Candidate for PEG/RBV therapy
Body mass index (BMI) between 18 and 36 kg/m2
Creatinine clearance >= 50 mL/min
Agree to use two forms of highly effective contraception methods for the duration of the study and for 7 months after the last dose study medication. Females of childbearing potential must have negative pregnancy test at Screening and Baseline

Exclusion Criteria:

Exceed defined thresholds for key laboratory parameters at Screening
Diagnosis of autoimmune disease, decompensated liver disease, poorly controlled diabetes mellitus, significant psychiatric illness, severe chronic obstructive pulmonary disease (COPD), HIV, hepatitis B virus (HBV), hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed
Subjects with current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone maintenance treatment for at least 6 months prior to Screening may be included into the study
Use of prohibited concomitant medications two weeks prior to baseline through the end of treatment

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Axis Clinical Trials	Los Angeles	California	United States	90036
2	Axis Clinical Trials	Los Angeles	California	United States	90057
3	UCLA Medical Center	Los Angeles	California	United States	90057
4	V.A. Greater Los Angeles Healthcare System	Los Angeles	California	United States	90073
5	UC Davis Medical Center	Sacramento	California	United States	95817
6	Research and Education, Inc.	San Diego	California	United States	92105
7	San Jose Gastroenterology	San Jose	California	United States	95116
8	Stanford University	Stanford	California	United States	94035
9	South Denver Gastroenterology	Englewood	Colorado	United States	80113
10	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana	United States	46237
11	Commonwealth Clinical Studies, LLC	Brockton	Massachusetts	United States	02302
12	Impact Clinical Trials	Las Vegas	Nevada	United States	89106
13	North Shore University Hospital	Great Neck	New York	United States	11021
14	Weill Cornell College of Medicine	New York	New York	United States	10021
15	Westchester Medical Center	Yonkers	New York	United States	10701
16	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina	United States	28801
17	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
18	Duke University	Durham	North Carolina	United States	27710
19	Oregon Health & Science University	Portland	Oregon	United States	97239
20	The North Texas Research Institute	Arlington	Texas	United States	76012
21	Research Specialists of Texas	Houston	Texas	United States	77030
22	University of Utah Pediatric Pulmonology	Salt Lake City	Utah	United States	84143
23	Metropolitan Liver Diseases Center	Fairfax	Virginia	United States	22031
24	Liver Institute of Virginia, Bon Secours Health System	Newport News	Virginia	United States	23602
25	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
26	Harborview Medical Center	Seattle	Washington	United States	98104
27	Royal Prince Alfred Hospital	Camperdown	New South Wales	Australia	2050
28	Concord Repatriation General Hospital	Concord	New South Wales	Australia	2137
29	Saint Vincents Hospital	Darlinghurst	New South Wales	Australia	2010
30	Nepean Hospital	Kingswood	New South Wales	Australia	2747
31	St. George Hospital	Kogarah	New South Wales	Australia	NSW 2217
32	Liverpool Hospital	Sydney	New South Wales	Australia	1871
33	Westmead Hospital	Westmead	New South Wales	Australia	2145
34	Royal Brisbane Hospital Research Foundation	Herston	Queensland	Australia	4029
35	Greenslopes Private Hospital	Woolloongabba	Queensland	Australia	4102
36	Princess Alexandra Hospital	Woolloongabba	Queensland	Australia	4102
37	Flinders Medical Centre	Bedford Park	South Australia	Australia	5042
38	St. Vincent's Hospital, Sydney Ltd.	Fitzroy	Victoria	Australia	3065
39	Western Hospital	Footscray	Victoria	Australia	VIC 3011
40	Austin Health, Department of Hepatology	Heidelberg	Victoria	Australia	3081
41	Alfred Hospital	Melbourne	Victoria	Australia	3004
42	Monash Medical Centre	Melbourne	Victoria	Australia	3004
43	Box Hill Hospital	Melbourne	Victoria	Australia	3128
44	Royal Melbourne Hospital	Parkville	Victoria	Australia	3050
45	Fremantle Hospital	Fremantle	Western Australia	Australia	6160
46	Sir Charles Gairdner Hospital	Nedlands	Western Australia	Australia	6009
47	University of Calgary	Calgary	Alberta	Canada	T2N4N1
48	University of Alberta	Edmonton	Alberta	Canada	T6G 2C8
49	LAIR Centre	Vancouver	British Columbia	Canada	V5Z 1H2
50	GIRI GI Research Institute	Vancouver	British Columbia	Canada	V6Z 2K5
51	University of Manitoba, John Buhler Research Centre	Winnipeg	Manitoba	Canada	R3E 3P4
52	London Health Sciences	London	Ontario	Canada	N6A5A5
53	Toronto Liver Centre	Toronto	Ontario	Canada	M6H 3M1
54	Auckland Hospital	Aukland		New Zealand
55	Waikato Hospital	Hamilton		New Zealand	3240