Oral Antivirals (GS-5885, Tegobuvir, and/or GS-9451) With Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects With Chronic Genotype 1 Hepatitis C Virus Infection

NCT ID: NCT01371578

Last Updated: 2014-02-11

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

163 participants

Study Classification

INTERVENTIONAL

Study Start Date

2011-07-31

Study Completion Date

2013-03-31

Brief Summary

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This is a Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Evaluating Response Guided Therapy using Combinations of Oral Antivirals (GS-5885, tegobuvir, and/or GS-9451) with Peginterferon Alfa 2a and Ribavirin in Treatment Experienced Subjects with Chronic Genotype 1 Hepatitis C Virus (HCV) Infection.

Detailed Description

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In September 2011, the FDA requested that Gilead make several major changes to this study because of side effects experienced by two patients in other Gilead studies.

In 2 HCV-infected people that were given tegobuvir with another experimental medication plus interferon and ribavirin, big reductions in the number of white blood cells, red blood cells and platelets were seen. Because these cases might have been related to tegobuvir when given with interferon, ribavirin and another direct antiviral agent, tegobuvir is no longer being given to people with these other medications in this study.

As a result, the study is now open label which means both you and your study doctor will know the medication you will be receiving and Arms 1 and 3 have been discontinued from the study.

All subjects enrolled in the study as of September 2nd 2011 will receive Response Guided Therapy (RGT) with both GS-5885 and GS-9451 plus PEG and RBV.

Conditions

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Hepatitis C, Chronic

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Arm 2

AM Dosing: One GS-5885 30 mg tablet, two GS-9451 100 mg tablets, orally with RBV and with food.

PM Dosing: RBV with food.

PEG, 180 µg, will be administered weekly by subcutaneous injection for the specified period of time (see Study Design). Pegasys® prefilled syringes (Hoffman-La Roche) will be supplied by Gilead Sciences.

Group Type EXPERIMENTAL

GS-5885 tablet

Intervention Type DRUG

30 mg active tablet

GS-9451 tablet

Intervention Type DRUG

two active 100 mg tablets

peginterferon alfa-2a

Intervention Type BIOLOGICAL

peginterferon alfa-2a (solution for injection) 180 µg/week

ribavirin tablet

Intervention Type DRUG

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

Interventions

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GS-5885 tablet

30 mg active tablet

Intervention Type DRUG

GS-9451 tablet

two active 100 mg tablets

Intervention Type DRUG

peginterferon alfa-2a

peginterferon alfa-2a (solution for injection) 180 µg/week

Intervention Type BIOLOGICAL

ribavirin tablet

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* Male or female, aged from 18 to 70 years old, inclusive
* Chronic HCV infection for at least 6 months prior to Baseline
* Subjects must have liver biopsy results (≤ 3 years prior to screening) indicating the absence of cirrhosis.
* Monoinfection with HCV genotype 1
* HCV RNA \> 10\^4 IU/mL at Screening
* Prior treatment and adherence (as defined by receiving at least 80% of the prescribed treatment) with one course of a pegylated interferon-alfa (Pegasys or Peg-Intron) 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

* Non-Responder: Subject did not achieve undetectable HCV RNA levels during or at the end of a treatment period of at least 12 weeks duration. Within Nonresponders, subjects will be further defined as Null or Partial Responders if they had \< 2 log10 or ≥ 2 log10 reduction, respectively, in HCV RNA during the first 12 weeks of treatment
* Responder: Subject achieved undetectable HCV RNA during treatment. Within Responders, subjects will be further defined as Relapsers if they had undetectable HCV RNA at the end of at least 42 weeks of treatment but detectable HCV RNA levels observed within 1 year of the end of treatment and Breakthrough subjects if they achieved undetectable HCV RNA levels during the treatment period but detectable HCV RNA at the end of treatment.
* No prior treatment with an oral HCV antiviral (exclusive of RBV).
* Body mass index (BMI) 18-36 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
* Creatinine clearance ≥ 50 mL/min.
* Agree to use two forms of highly effective contraception for the duration of the study and for 6 months after the last dose of study medication. Females of childbearing potential must have a negative pregnancy test at Screening and Baseline

Exclusion Criteria

* Discontinued prior treatment with pegylated interferon-alfa and RBV due to an adverse event, toxicity reasons or were lost to follow-up.
* Exceed defined thresholds for leukopenia, neutropenia, anemia, thrombocytopenia, 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), or another HCV genotype, hepatocellular carcinoma or other malignancy (with exception of certain skin cancers), hemoglobinopathy, retinal disease, or are immunosuppressed.
* Current use of amphetamines, cocaine, opiates (e.g., morphine, heroin), or ongoing alcohol abuse are excluded. Subjects on stable methadone are excluded, however stable buprenorphine maintenance treatment for at least 6 months is not exclusionary
* Receiving any of the prohibited concomitant medications.
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Gilead Sciences

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Bittoo Kanwar, MD

Role: STUDY_CHAIR

Gilead Sciences

Locations

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Digestive Health Specialists of the Southeast

Dothan, Alabama, United States

Site Status

Alabama Liver and Digestive Specialists

Montgomery, Alabama, United States

Site Status

California Liver Institute

Beverly Hills, California, United States

Site Status

Scripps Clinic

La Jolla, California, United States

Site Status

University of California Davis Medical Center

Sacramento, California, United States

Site Status

RESEARCH and EDUCATION, INC

San Diego, California, United States

Site Status

Medical Associates Research Group

San Diego, California, United States

Site Status

Kaiser Permanente

San Diego, California, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

South Denver Gastroenterology

Englewood, Colorado, United States

Site Status

Bach and Godofsky Infectious Diseases

Bradenton, Florida, United States

Site Status

University of Florida

Gainesville, Florida, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Orlando Immunology Center

Orlando, Florida, United States

Site Status

South Florida Center of Gastroenterology, LLC

Wellington, Florida, United States

Site Status

Emory University, Infectious Disease Clinic

Atlanta, Georgia, United States

Site Status

Digestive Healthcare of Georgia

Atlanta, Georgia, United States

Site Status

Dekalb Gastroenterology

Decatur, Georgia, United States

Site Status

Gastrointestinal Specialists of Georgia PC

Marietta, Georgia, United States

Site Status

Indiana University

Indianapolis, Indiana, United States

Site Status

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, United States

Site Status

Graves Gilbert Clinic

Bowling Green, Kentucky, United States

Site Status

Gastroenterology Associates, LLC

Baton Rouge, Louisiana, United States

Site Status

Digestive Disease Associates, PA

Baltimore, Maryland, United States

Site Status

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Site Status

Partners in Internal Medicine, P.C.

Worcester, Massachusetts, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Gastrointestinal Associates, PA

Jackson, Mississippi, United States

Site Status

Digestive Health Specialists, PA

Tupelo, Mississippi, United States

Site Status

ID Care 105

Hillsborough, New Jersey, United States

Site Status

Atlantic Research Affiliates, LLC

Morristown, New Jersey, United States

Site Status

Southwest CARE Center

Santa Fe, New Mexico, United States

Site Status

Binghamton Gastroenterology

Binghamton, New York, United States

Site Status

North Shore University Hospital

Manhasset, New York, United States

Site Status

Concorde Medical Group

New York, New York, United States

Site Status

Cornell University Gastroenterology & Hepatology

New York, New York, United States

Site Status

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, United States

Site Status

Duke University Medical Center

Durham, North Carolina, United States

Site Status

Cumberland Research Associates, LLC

Fayetteville, North Carolina, United States

Site Status

University of Cincinnati

Cincinnati, Ohio, United States

Site Status

Options Health Research, LLC

Tulsa, Oklahoma, United States

Site Status

University Gastroenterology

Providence, Rhode Island, United States

Site Status

Memphis Gastroenterology Group

Germantown, Tennessee, United States

Site Status

Columbia Medical Group, The Frist Clinic

Nashville, Tennessee, United States

Site Status

Nashville Medical Research Institute

Nashville, Tennessee, United States

Site Status

Nashville Gastrointestinal Specialists, Inc

Nashville, Tennessee, United States

Site Status

The North Texas Research Institute

Arlington, Texas, United States

Site Status

Baylor University Medical Center

Dallas, Texas, United States

Site Status

Kelsey Research Foundation

Houston, Texas, United States

Site Status

Research Specialists of Texas

Houston, Texas, United States

Site Status

Metropolitan Research

Fairfax, Virginia, United States

Site Status

Digestive and Liver Disease Specialists

Norfolk, Virginia, United States

Site Status

Liver Institute of Virginia

Richmond, Virginia, United States

Site Status

Virginia Mason Medical Center, Digestive Disease Institute

Seattle, Washington, United States

Site Status

Fundacion de Investigacion de Diego

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

Other Identifiers

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GS-US-256-0124

Identifier Type: -

Identifier Source: org_study_id

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