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

NCT01384383 | Terminated Phase 2

• 1 other identifier: GS-US-248-0121
• Study Type: interventional
• Target: 248
• Locations: 4 countries
• Sites: 55

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.

Conditions

Chronic Hepatitis C

Keywords

Chronic Hepatitis C; IL28B CC Genotype; Treatment naive; Peginterferon α-2a (PEG); Genotype 1a/b; GS 9451; GS 5885; Ribavirin (RBV); HCV NS5A inhibitor; HCV NS3 protease inhibitor

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Safety and tolerability of therapy

  Up to 48 weeks

• Virologic response

  Weeks 2, 4, 6, 8, 10, and 12

• Compare SVR

  Weeks 30 and 36

• Viral resistance

  Up to 96 Weeks

Study Arms (2)

Arm 1

EXPERIMENTAL

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; Drug: GS-9451; Drug: RBV; Drug: PEG

Arm 2

EXPERIMENTAL

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

Drug: RBV; Drug: PEG

Interventions

GS-5885 DRUG

GS-5885 30 mg tablet administered orally once daily

Arm 1

GS-9451 DRUG

GS-9451 200 mg tablet administered orally once daily

Arm 1

RBV DRUG

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)

Arm 1; Arm 2

PEG DRUG

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

Arm 1; Arm 2

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (55)

Axis Clinical Trials

Los Angeles, California, 90036, United States

Location

Axis Clinical Trials

Los Angeles, California, 90057, United States

Location

UCLA Medical Center

Los Angeles, California, 90057, United States

Location

V.A. Greater Los Angeles Healthcare System

Los Angeles, California, 90073, United States

Location

UC Davis Medical Center

Sacramento, California, 95817, United States

Location

Research and Education, Inc.

San Diego, California, 92105, United States

Location

San Jose Gastroenterology

San Jose, California, 95116, United States

Location

Stanford University

Stanford, California, 94035, United States

Location

South Denver Gastroenterology

Englewood, Colorado, 80113, United States

Location

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, 46237, United States

Location

Commonwealth Clinical Studies, LLC

Brockton, Massachusetts, 02302, United States

Location

Impact Clinical Trials

Las Vegas, Nevada, 89106, United States

Location

North Shore University Hospital

Great Neck, New York, 11021, United States

Location

Weill Cornell College of Medicine

New York, New York, 10021, United States

Location

Westchester Medical Center

Yonkers, New York, 10701, United States

Location

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, 28801, United States

Location

The University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

Duke University

Durham, North Carolina, 27710, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

The North Texas Research Institute

Arlington, Texas, 76012, United States

Location

Research Specialists of Texas

Houston, Texas, 77030, United States

Location

University of Utah Pediatric Pulmonology

Salt Lake City, Utah, 84143, United States

Location

Metropolitan Liver Diseases Center

Fairfax, Virginia, 22031, United States

Location

Liver Institute of Virginia, Bon Secours Health System

Newport News, Virginia, 23602, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Harborview Medical Center

Seattle, Washington, 98104, United States

Location

Royal Prince Alfred Hospital

Camperdown, New South Wales, 2050, Australia

Location

Concord Repatriation General Hospital

Concord, New South Wales, 2137, Australia

Location

Saint Vincents Hospital

Darlinghurst, New South Wales, 2010, Australia

Location

Nepean Hospital

Kingswood, New South Wales, 2747, Australia

Location

St. George Hospital

Kogarah, New South Wales, NSW 2217, Australia

Location

Liverpool Hospital

Sydney, New South Wales, 1871, Australia

Location

Westmead Hospital

Westmead, New South Wales, 2145, Australia

Location

Royal Brisbane Hospital Research Foundation

Herston, Queensland, 4029, Australia

Location

Greenslopes Private Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Princess Alexandra Hospital

Woolloongabba, Queensland, 4102, Australia

Location

Flinders Medical Centre

Bedford Park, South Australia, 5042, Australia

Location

St. Vincent's Hospital, Sydney Ltd.

Fitzroy, Victoria, 3065, Australia

Location

Western Hospital

Footscray, Victoria, VIC 3011, Australia

Location

Austin Health, Department of Hepatology

Heidelberg, Victoria, 3081, Australia

Location

Alfred Hospital

Melbourne, Victoria, 3004, Australia

Location

Monash Medical Centre

Melbourne, Victoria, 3004, Australia

Location

Box Hill Hospital

Melbourne, Victoria, 3128, Australia

Location

Royal Melbourne Hospital

Parkville, Victoria, 3050, Australia

Location

Fremantle Hospital

Fremantle, Western Australia, 6160, Australia

Location

Sir Charles Gairdner Hospital

Nedlands, Western Australia, 6009, Australia

Location

University of Calgary

Calgary, Alberta, T2N4N1, Canada

Location

University of Alberta

Edmonton, Alberta, T6G 2C8, Canada

Location

LAIR Centre

Vancouver, British Columbia, V5Z 1H2, Canada

Location

GIRI GI Research Institute

Vancouver, British Columbia, V6Z 2K5, Canada

Location

University of Manitoba, John Buhler Research Centre

Winnipeg, Manitoba, R3E 3P4, Canada

Location

London Health Sciences

London, Ontario, N6A5A5, Canada

Location

Toronto Liver Centre

Toronto, Ontario, M6H 3M1, Canada

Location

Auckland Hospital

Aukland, New Zealand

Location

Waikato Hospital

Hamilton, 3240, New Zealand

Location

MeSH Terms

Conditions

Hepatitis C, Chronic

Interventions

ledipasvir; GS-9451

Condition Hierarchy (Ancestors)

Hepatitis C; Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2011
• First Posted: June 29, 2011
• Study Start: August 1, 2011
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: February 3, 2014

Record last verified: 2014-01

Locations

AU (20); CA (7); US (26); NZ (2)