GS-5885, GS-9451, Tegobuvir and Ribovirin in Treatment-Experienced Subjects With Chronic Genotype 1a Or 1b Hepatitis C Virus (HCV) Infection

NCT01435226 | Completed Phase 2 DMC

• 1 other identifier: GS-US-248-0131
• Study Type: interventional
• Target: 170
• Locations: 2 countries
• Sites: 51

Brief Summary

This is a Phase 2 Randomized, Double-Blind, Placebo-Controlled Study of GS-5885, GS-9451, Tegobuvir and Ribavirin (RBV) Compared with GS-5885, GS-9451 with Tegobuvir or RBV in Treatment-Experienced Subjects with Chronic Genotype 1a or 1b Hepatitis C Virus (HCV) Infection.

Conditions

Hepatitis C, Chronic

Keywords

Hepatitis C; HCV; Rapid Virologic Response; Sustained Virologic Response; Direct Acting Antiviral; Combination Therapy; Tegobuvir; Treatment Experienced; HCV RNA; Polymerase inhibitor; Protease inhibitor; Interferon intolerant; Interferon ineligible; GS-9190; GS-9451; GS-5885; Chronic Genotype 1a or 1b

Outcome Measures

Primary Outcomes (2)

• Safety and Tolerability

  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.

  24 weeks

• Antiviral Activity

  To evaluate the antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< lower limit of quantitation \[LLoQ\] 24 weeks post-treatment) of combination therapy with GS-5885, GS-9451, tegobuvir and RBV compared with GS-5885, GS-9451 and tegobuvir or GS-5885, GS-9451 and RBV in treatment-experienced subjects with chronic genotype 1a or 1b HCV infection

  24 weeks

Secondary Outcomes (3)

• Viral Dynamics

  10 days

• Composite (or Profile) of Pharmacokinetics Composite (or Profile) of Pharmacokinetics

  predose, 1, 2, 3, 4, 6, 8, 10, 12 and 24 hours post-dose

• Antiviral Efficacy

  24-48 weeks

Study Arms (3)

Arm 1

ACTIVE COMPARATOR

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV BID

Drug: GS-5885; Drug: GS-9451; Drug: tegobuvir; Drug: Ribavirin

Arm 2

ACTIVE COMPARATOR

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir 30 mg BID + RBV placebo BID

Drug: GS-5885; Drug: GS-9451; Drug: tegobuvir; Drug: placebo to match RBV

Arm 3

ACTIVE COMPARATOR

GS-5885 90 mg QD + GS-9451 200 mg QD + tegobuvir placebo BID + RBV BID

Drug: GS-5885; Drug: GS-9451; Drug: placebo to match tegobuvir; Drug: Ribavirin

Interventions

GS-5885 DRUG

Drug: GS-5885 tablet GS-5885 tablet, 90 mg, QD

Arm 1; Arm 2; Arm 3

GS-9451 DRUG

Drug: GS-9451 tablet GS-9451 tablet, 200 mg QD

Arm 1; Arm 2; Arm 3

tegobuvir DRUG

tegobuvir 30 mg BID

Arm 1; Arm 2

placebo to match tegobuvir DRUG

tegobuvir placebo BID

Arm 3

placebo to match RBV DRUG

Ribovirin placebo BID

Arm 2

Ribavirin DRUG

Ribavirin (Copegus®) BID (1000 mg for subjects weighing \< 75 kg and 1200 mg for subjects weighing ≥ 75 kg) divided BID

Arm 1; Arm 3

Eligibility Criteria

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

You may qualify if:

• Age ≥18 years with chronic HCV infection
• Liver biopsy results ≤ 3 years prior to screening indicating the absence of cirrhosis. Alternatively, a non-invasive procedure conducted within 6 months of screening is permitted in countries where allowed
• Monoinfection with HCV genotype (GT) 1a or 1b
• HCV RNA ≥ 104 IU/mL at screening
• Prior treatment and adherence with one course of pegylated interferon alfa and RBV
• The subject's medical records must include sufficient detail of prior treatment with pegylated interferon alfa and RBV (start/stop dates and viral response) to allow for categorization of prior response as either null, partial, breakthrough or relapse.
• Body mass index (BMI) 18-40 kg/m2 inclusive
• Screening ECG without clinically significant abnormalities and with QTcF interval (QT corrected using Fridericia's formula)
• ≤ 450 msec for males and ≤ 470 msec for females.
• Agree to use two forms of highly effective contraception for the duration of the study and for 7 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at screening and baseline.

You may not qualify if:

• Discontinuation of prior treatment with pegylated interferon alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up
• History of significant cardiac disease
• Exceed criteria delineated in Section 4.2 for laboratory measure thresholds related to leukopenia, neutropenia, anemia, thrombocytopenia, and thyroid stimulating hormone (TSH).
• 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 resolved skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
• Current abuse of amphetamines, cocaine, opiates, or alcohol. Methadone use is not allowed, however stable buprenorphine maintenance treatment for ≥ 6 months is permitted.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (51)

University of Arizona

Tucson, Arizona, 85724, United States

Location

Advanced Clinical Research Institute, LLC

Anaheim, California, 92801, United States

Location

California Liver Institute

Beverly Hills, California, 90211, United States

Location

SCTI Research Foundation Liver Center

Coronado, California, 92118, United States

Location

University of California, San Diego

La Jolla, California, 92161, United States

Location

Lightsource Medical

Los Angeles, California, 90036, United States

Location

Medical Associates Research Group, Inc.

San Diego, California, 92123, United States

Location

Kaiser Permanente

San Diego, California, 92154, United States

Location

California Pacific Medical Center

San Francisco, California, 94115, United States

Location

San Jose Gastroenterology

San Jose, California, 95128, United States

Location

Whitman Walker Clinic

Washington D.C., District of Columbia, 20037, United States

Location

Avail Clinical Research, LLC

DeLand, Florida, 32720, United States

Location

University of Miami, Center for Liver Diseases

Miami, Florida, 33136, United States

Location

Infectious Disease Specialists of Atlanta

Decatur, Georgia, 30033, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Mercy Medical Center

Baltimore, Maryland, 21202, United States

Location

Johns Hopkins University

Lutherville, Maryland, 21093, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Novi, Michigan, 48377, United States

Location

Weill Medical College of Cornell Univeristy

New York, New York, 10021, United States

Location

Mount Sinai School of Medicine

New York, New York, 10029, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

University Gastroenterology

Providence, Rhode Island, 02905, United States

Location

Gastro One

Germantown, Tennessee, 38138, United States

Location

Southwest Infectious Disease Clinical Research, Inc

Dallas, Texas, 75204, United States

Location

University of Texas Medical Branch

Galveston, Texas, 77555, United States

Location

Therapeutic Concepts, PA

Houston, Texas, 77004, United States

Location

The University of Texas Health Sciences Center at Houston

Houston, Texas, 77030, United States

Location

Alamo Medical Research, Ltd.

San Antonio, Texas, 78215, United States

Location

University of Utah

Salt Lake City, Utah, 84132, United States

Location

Bon Secours St. Mary's Hospital of Richmond, Inc.

Newport News, Virginia, 23602, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Virginia Mason Medical Center

Seattle, Washington, 98101, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

Leber- and Studienzentrum am Checkpoint

Berlin, 10969, Germany

Location

Charite - Universitatsmedizin Berlin Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

Universitätsklinikum Bonn

Bonn, 53105, Germany

Location

Center for HIV and Hepatogastroenterology

Düsseldorf, 40237, Germany

Location

Klinikum der Johann Wolfgang Goethe Universitaet

Frankfurt, 60590, Germany

Location

Medizinische Universitatsklinik

Freiburg im Breisgau, 79106, Germany

Location

Universitatsklinikum Hamburg-Eppendorf

Hamburg, 22589, Germany

Location

Medizinische Hochschule Hannover

Hanover, 30625, Germany

Location

Klinikum der Universität Heidelberg

Heidelberg, 69120, Germany

Location

Gastroenterologisch-Hepatologisches Zentrum Kiel

Kiel, 24146, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Johannes Gutenberg University Hospital

Mainz, 55131, Germany

Location

Klinikum Innenstadt der LMU Munchen

München, 81377, Germany

Location

Universitätsklinikum Würzburg - Med Klinik und Poliklinik

Würzburg, 97080, Germany

Location

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C

Interventions

ledipasvir; GS-9451; tegobuvir; Ribavirin

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Ribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• John McNally, PhD

  Gilead Sciences

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2011
• First Posted: September 16, 2011
• Study Start: September 1, 2011
• Primary Completion: January 1, 2013
• Study Completion: July 1, 2013
• Last Updated: December 17, 2013

Record last verified: 2013-11

Locations

DE (14); US (37)