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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01384383
• Other study ID #: GS-US-248-0121
• Status: Terminated
• Phase: Phase 2
• First received: June 22, 2011
• Last updated: January 2, 2014
• Start date: August 2011
• Est. completion date: June 2013

Study information

• Verified date: January 2014
• Source: Gilead Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 248
• Est. completion date: June 2013
• Est. primary completion date: June 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Virus Diseases

Intervention

Drug:
• GS-5885
GS-5885 30 mg tablet administered orally once daily
• GS-9451
GS-9451 200 mg tablet administered orally once daily
• 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)
• PEG
Pegylated interferon alfa-2a (PEG) 180 µg administered once weekly by subcutaneous injection

Locations

Country	Name	City	State
Australia	Flinders Medical Centre	Bedford Park	South Australia
Australia	Royal Prince Alfred Hospital	Camperdown	New South Wales
Australia	Concord Repatriation General Hospital	Concord	New South Wales
Australia	Saint Vincents Hospital	Darlinghurst	New South Wales
Australia	St. Vincent's Hospital, Sydney Ltd.	Fitzroy	Victoria
Australia	Western Hospital	Footscray	Victoria
Australia	Fremantle Hospital	Fremantle	Western Australia
Australia	Austin Health, Department of Hepatology	Heidelberg	Victoria
Australia	Royal Brisbane Hospital Research Foundation	Herston	Queensland
Australia	Nepean Hospital	Kingswood	New South Wales
Australia	St. George Hospital	Kogarah	New South Wales
Australia	Alfred Hospital	Melbourne	Victoria
Australia	Box Hill Hospital	Melbourne	Victoria
Australia	Monash Medical Centre	Melbourne	Victoria
Australia	Sir Charles Gairdner Hospital	Nedlands	Western Australia
Australia	Royal Melbourne Hospital	Parkville	Victoria
Australia	Liverpool Hospital	Sydney	New South Wales
Australia	Westmead Hospital	Westmead	New South Wales
Australia	Greenslopes Private Hospital	Woolloongabba	Queensland
Australia	Princess Alexandra Hospital	Woolloongabba	Queensland
Canada	University of Calgary	Calgary	Alberta
Canada	University of Alberta	Edmonton	Alberta
Canada	London Health Sciences	London	Ontario
Canada	Toronto Liver Centre	Toronto	Ontario
Canada	GIRI GI Research Institute	Vancouver	British Columbia
Canada	LAIR Centre	Vancouver	British Columbia
Canada	University of Manitoba, John Buhler Research Centre	Winnipeg	Manitoba
New Zealand	Auckland Hospital	Aukland
New Zealand	Waikato Hospital	Hamilton
United States	The North Texas Research Institute	Arlington	Texas
United States	Asheville Gastroenterology Associates, P.A.	Asheville	North Carolina
United States	Commonwealth Clinical Studies, LLC	Brockton	Massachusetts
United States	The University of North Carolina at Chapel Hill	Chapel Hill	North Carolina
United States	Duke University	Durham	North Carolina
United States	South Denver Gastroenterology	Englewood	Colorado
United States	Metropolitan Liver Diseases Center	Fairfax	Virginia
United States	North Shore University Hospital	Great Neck	New York
United States	Research Specialists of Texas	Houston	Texas
United States	Indianapolis Gastroenterology Research Foundation	Indianapolis	Indiana
United States	Impact Clinical Trials	Las Vegas	Nevada
United States	Axis Clinical Trials	Los Angeles	California
United States	Axis Clinical Trials	Los Angeles	California
United States	UCLA Medical Center	Los Angeles	California
United States	V.A. Greater Los Angeles Healthcare System	Los Angeles	California
United States	Weill Cornell College of Medicine	New York	New York
United States	Liver Institute of Virginia, Bon Secours Health System	Newport News	Virginia
United States	Digestive and Liver Disease Specialists	Norfolk	Virginia
United States	Oregon Health & Science University	Portland	Oregon
United States	UC Davis Medical Center	Sacramento	California
United States	University of Utah Pediatric Pulmonology	Salt Lake City	Utah
United States	Research and Education, Inc.	San Diego	California
United States	San Jose Gastroenterology	San Jose	California
United States	Harborview Medical Center	Seattle	Washington
United States	Stanford University	Stanford	California
United States	Westchester Medical Center	Yonkers	New York

Sponsors (1)

Lead Sponsor	Collaborator
Gilead Sciences

Countries where clinical trial is conducted

United States,  Australia,  Canada,  New Zealand, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sustained virologic response (SVR)	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.	30 , 36 or 48 weeks	No
Secondary	Safety and tolerability of therapy	Safety and tolerability of the therapy is measured by frequency of laboratory abnormalities , reported adverse events and discontinuations due to adverse events.	Up to 48 weeks	No
Secondary	Virologic response	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	Weeks 2, 4, 6, 8, 10, and 12	No
Secondary	Compare SVR	Compare SVR following treatment with GS-5885 + GS-9451 + PEG/RBV for 6 weeks versus 12 weeks.	Weeks 30 and 36	No
Secondary	Viral resistance	Characterize viral resistance to GS-5885 and GS-9451 when administered in combination with PEG/RBV	Up to 96 Weeks	No