GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) in Interferon Ineligible or Intolerant Subjects With Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection

Sponsor

Gilead Sciences (Industry)

Overall Status

Completed

CT.gov ID

NCT01434498

Collaborator

(none)

163

Enrollment

Locations

Arms

Duration (Months)

3.3

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects with Chronic Genotype 1a or 1b HCV Infection.

Condition or Disease	Intervention/Treatment	Phase
Chronic Genotype 1a or 1b HCV Infection	Drug: GS-5885 tablet Drug: GS-9451 tablet Drug: tegobuvir capsule Drug: ribavirin tablet Drug: placebo matching ribavirin tablet Device: placebo matching tegobuvir capsule	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

163 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin; GS-5885, GS-9451 and Tegobuvir; GS-5885, GS-9451 and Ribavirin in Interferon Ineligible or Intolerant Subjects With Chronic Genotype 1a or 1b HCV Infection (Protocol No. GS US 248 0132)

Study Start Date :

Sep 1, 2011

Actual Primary Completion Date :

Jan 1, 2013

Actual Study Completion Date :

Jan 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm 1 GS-5885, GS-9451, tegobuvir (GS-9190), and Copegus® for 24 weeks	Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: tegobuvir capsule tegobuvir capsule, 30 mg BID Drug: ribavirin tablet ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)
Active Comparator: Arm 2 GS-5885, GS-9451, tegobuvir (GS-9190), and a placebo matching ribavirin for 24 weeks	Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: tegobuvir capsule tegobuvir capsule, 30 mg BID Drug: placebo matching ribavirin tablet placebo matching ribavirin tablet, BID
Active Comparator: Arm 3 GS-5885, GS-9451, a placebo matching tegobuvir, and Copegus® for 24 weeks	Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD Drug: ribavirin tablet ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID) Device: placebo matching tegobuvir capsule placebo matching tegobuvir capsule, BID

Arm

Intervention/Treatment

Active Comparator: Arm 1

GS-5885, GS-9451, tegobuvir (GS-9190), and Copegus® for 24 weeks

Drug: GS-5885 tablet

GS-5885 tablet, 90 mg, QD

Drug: GS-9451 tablet

GS-9451 tablet, 200 mg QD

Drug: tegobuvir capsule

tegobuvir capsule, 30 mg BID

Drug: ribavirin tablet

ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)

Active Comparator: Arm 2

GS-5885, GS-9451, tegobuvir (GS-9190), and a placebo matching ribavirin for 24 weeks

Drug: GS-5885 tablet

GS-5885 tablet, 90 mg, QD

Drug: GS-9451 tablet

GS-9451 tablet, 200 mg QD

Drug: tegobuvir capsule

tegobuvir capsule, 30 mg BID

Drug: placebo matching ribavirin tablet

placebo matching ribavirin tablet, BID

Active Comparator: Arm 3

GS-5885, GS-9451, a placebo matching tegobuvir, and Copegus® for 24 weeks

Drug: GS-5885 tablet

GS-5885 tablet, 90 mg, QD

Drug: GS-9451 tablet

GS-9451 tablet, 200 mg QD

Drug: ribavirin tablet

ribavirin tablet (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID)

Device: placebo matching tegobuvir capsule

placebo matching tegobuvir capsule, BID

Outcome Measures

Primary Outcome Measures

Safety and Tolerability [Through 24 weeks of off-treatment follow-up]
To evaluate safety and tolerability of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs and 12-lead ECGs at various time points during the study.
Antiviral Activity [Through 24 weeks of off-treatment follow-up]
To evaluate antiviral efficacy as measured by sustained virologic response (defined as HCV RNA < lower limit of quantitation 24-weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and ribavirin or GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and ribavirin.

Secondary Outcome Measures

Viral Dynamics [Through 10 days of therapy]
To characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 10 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-5885, GS-9451 and tegobuvir.
Composite (or Profile) of Pharmacokinetics [predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose]
To characterize the steady state pharmacokinetics of GS-5885, GS-9451, tegobuvir and ribavirin (if appropriate). Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau and T ½

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult subjects 18 and older with chronic HCV infection
Liver biopsy results (performed no more than 3 years prior to Screening) indicating the absence of cirrhosis
Monoinfection with HCV genotype 1a or 1b
Interferon ineligible or intolerant
Body mass index (BMI) between 18 and 40 kg/m2
Use of highly effective contraception methods if female of childbearing potential or sexually active male
Screening laboratory values within defined thresholds
Has not been exposed to any investigational drug or device within 30 days of the Screening visit
Able to comply with the dosing instructions for study drug administration and able to complete the study schedule of assessments

Exclusion Criteria:

Prior treatment of HCV with any direct-acting antiviral (whether approved or experimental)
Decompensated liver disease or cirrhosis
Co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
History of difficulty with blood collection and/or poor venous access
Pregnant or nursing female or male with pregnant female partner
Chronic liver disease of a non-HCV etiology
Suspicion of hepatocellular carcinoma
Clinically-relevant drug abuse

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	California Liver Institute	Beverly Hills	California	United States	90211
2	SCTI Research Foundation Liver Center	Coronado	California	United States	92118
3	Scripps Clinic	La Jolla	California	United States	92037
4	University of California, San Diego	La Jolla	California	United States	92161
5	Kaiser Permanente Medical Center	Los Angeles	California	United States	90027
6	Lightsource Medical	Los Angeles	California	United States	90036
7	Medical Associates Research Group, Inc.	San Diego	California	United States	92123
8	Kaiser Permanente	San Diego	California	United States	92154
9	California Pacific Medical Center	San Francisco	California	United States	94115
10	University of Colorado	Aurora	Colorado	United States	80045
11	University of Miami, Center for Liver Diseases	Miami	Florida	United States	33136
12	Orlando Immunology Center (ACH)	Orlando	Florida	United States	32803-1851
13	Gastrointestinal Specialists of Georgia, PC	Marietta	Georgia	United States	30060
14	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana	United States	46237
15	University of Kansas Medical Center	Kansas City	Kansas	United States	66160
16	Johns Hopkins University	Lutherville	Maryland	United States	21093
17	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
18	Beth Israel Deconess Medical Center	Boston	Massachusetts	United States	02215
19	The Research Institute	Springfield	Massachusetts	United States	01105
20	Henry Ford Health System	Novi	Michigan	United States	48377
21	Saint Michael's Medical Center	Newark	New Jersey	United States	07102
22	Weill Cornell Medical College	New York	New York	United States	10021
23	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina	United States	28801
24	University of North Carolina at Chapel Hill	Chapel Hill	North Carolina	United States	27599
25	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
26	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania	United States	19107
27	University Gastroenterology	Providence	Rhode Island	United States	02905
28	Gastro One	Germantown	Tennessee	United States	38138
29	The North Texas Research Institute	Arlington	Texas	United States	76012
30	The University of Texas Medical Branch	Galveston	Texas	United States	77555
31	The University of Texas Health Sciences Center at Houston	Houston	Texas	United States	77030
32	Alamo Medical Research	San Antonio	Texas	United States	78215
33	Inova Fairfax Hospital Center for Liver Diseases	Falls Church	Virginia	United States	22042
34	Bon Secours St. Mary's Hospital of Richmond, Inc.	Newport News	Virginia	United States	23602
35	Digestive and Liver Disease Specialists	Norfolk	Virginia	United States	23502
36	Virginia Mason Medical Center	Seattle	Washington	United States	98101
37	University of Calgary	Calgary	Alberta	Canada	T2N 4Z6
38	University Of Alberta Hospital	Edmonton	Alberta	Canada	T6G 2C8
39	University of Alberta	Edmonton	Alberta	Canada	T6G 2X8
40	Gordon & Leslie Diamond Health Care Centre	Vancouver	British Columbia	Canada	V5Z 1M9
41	University of British Columbia	Vancouver	British Columbia	Canada	V6Z 2C9
42	GIRI GI Research Institute	Vancouver	British Columbia	Canada	V6Z 2K5
43	University of Manitoba	Winnipeg	Manitoba	Canada	R3E 3P4
44	London Health Sciences Centre	London	Ontario	Canada	N6A 5A5
45	The Ottawa Hospital	Ottawa	Ontario	Canada	K1H 8L6
46	Toronto General Hospital, University Health Network	Toronto	Ontario	Canada	M5G 2C4
47	Toronto General Hospital, University Health Network	Toronto	Ontario	Canada	M5G 2N2
48	Toronto Western Hospital	Toronto	Ontario	Canada	M5T2S8
49	Hospital Saint-Luc DU CHUM	Montreal	Quebec	Canada	H2X3J4
50	Clinical Research Puerto Rico Inc	San Juan		Puerto Rico	00909-1711