NCT01371578

Brief Summary

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
163

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jul 2011

Geographic Reach
2 countries

55 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 9, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

June 13, 2011

Completed
18 days until next milestone

Study Start

First participant enrolled

July 1, 2011

Completed
1.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2013

Completed
Last Updated

February 11, 2014

Status Verified

January 1, 2014

Enrollment Period

1.7 years

First QC Date

June 9, 2011

Last Update Submit

January 14, 2014

Conditions

Keywords

Hepatitis CHCVRapid Virologic ResponseSustained Virologic ResponseDirect Acting AntiviralCombination Therapy HCV RNAPolymerase inhibitorProtease inhibitorTreatment naĂ¯veGS-5885GS-9190TegobuvirGS-9451

Outcome Measures

Primary Outcomes (1)

  • Sustained Virologic Response (SVR)

    To evaluate antiviral efficacy as measured by sustained virologic response (SVR, defined as HCV RNA \< Lower Limit of Quantification (LLoQ) 24 weeks post-treatment) of response guided therapy (RGT) with GS-9451 + GS-5885, with peginterferon alfa-2a (PEG) and ribavirin (RBV) in treatment-experienced subjects.

    through 24 weeks of off-treatment follow-up

Secondary Outcomes (5)

  • Sustained Virologic Response(SVR) of each regimen administered for 24 to 48 weeks

    Weeks 1, 2, 4, 8, 12, 16, 20, 24, 36, 48 and at 4 and 12 weeks off-treatment

  • Safety and Tolerability

    through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up

  • Characterize the viral dynamics of GS-5885, GS-9451 when administered in combination with PEG and RBV

    Through Week 2 of therapy

  • Characterize the pharmacokinetics of GS-5885 and GS-9451 when administered in combination with PEG and RBV

    Through Week 2 of therapy

  • Emergence of Viral Resistance

    through 24 to 48 week treatment period and up to 24 weeks of off-treatment follow-up

Study Arms (1)

Arm 2

EXPERIMENTAL

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.

Drug: GS-5885 tabletDrug: GS-9451 tabletBiological: peginterferon alfa-2aDrug: ribavirin tablet

Interventions

30 mg active tablet

Arm 2

two active 100 mg tablets

Arm 2

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

Arm 2

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

Arm 2

Eligibility Criteria

Age18 Years - 80 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.
  • Receiving any of the prohibited concomitant medications.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (55)

Digestive Health Specialists of the Southeast

Dothan, Alabama, 36305, United States

Location

Alabama Liver and Digestive Specialists

Montgomery, Alabama, 36116, United States

Location

California Liver Institute

Beverly Hills, California, 90211, United States

Location

Scripps Clinic

La Jolla, California, 92037, United States

Location

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

RESEARCH and EDUCATION, INC

San Diego, California, 92015, United States

Location

Medical Associates Research Group

San Diego, California, 92123, United States

Location

Kaiser Permanente

San Diego, California, 92154, United States

Location

University of Colorado Denver

Aurora, Colorado, 80045, United States

Location

South Denver Gastroenterology

Englewood, Colorado, 80110, United States

Location

Bach and Godofsky Infectious Diseases

Bradenton, Florida, 34209, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

University of Miami

Miami, Florida, 33136, United States

Location

Orlando Immunology Center

Orlando, Florida, 32803, United States

Location

South Florida Center of Gastroenterology, LLC

Wellington, Florida, 33414, United States

Location

Emory University, Infectious Disease Clinic

Atlanta, Georgia, 30308, United States

Location

Digestive Healthcare of Georgia

Atlanta, Georgia, 30309, United States

Location

Dekalb Gastroenterology

Decatur, Georgia, 30033, United States

Location

Gastrointestinal Specialists of Georgia PC

Marietta, Georgia, 30060, United States

Location

Indiana University

Indianapolis, Indiana, 46202, United States

Location

Indianapolis Gastroenterology Research Foundation

Indianapolis, Indiana, 46237, United States

Location

Graves Gilbert Clinic

Bowling Green, Kentucky, 42101, United States

Location

Gastroenterology Associates, LLC

Baton Rouge, Louisiana, 70809, United States

Location

Digestive Disease Associates, PA

Baltimore, Maryland, 21229, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Partners in Internal Medicine, P.C.

Worcester, Massachusetts, 01608, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Gastrointestinal Associates, PA

Jackson, Mississippi, 39202, United States

Location

Digestive Health Specialists, PA

Tupelo, Mississippi, 38801, United States

Location

ID Care 105

Hillsborough, New Jersey, 08844, United States

Location

Atlantic Research Affiliates, LLC

Morristown, New Jersey, 07960, United States

Location

Southwest CARE Center

Santa Fe, New Mexico, 87505, United States

Location

Binghamton Gastroenterology

Binghamton, New York, 13903, United States

Location

North Shore University Hospital

Manhasset, New York, 11030, United States

Location

Concorde Medical Group

New York, New York, 10016, United States

Location

Cornell University Gastroenterology & Hepatology

New York, New York, 10021, United States

Location

Asheville Gastroenterology Associates, P.A.

Asheville, North Carolina, 28801, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cumberland Research Associates, LLC

Fayetteville, North Carolina, 28304, United States

Location

University of Cincinnati

Cincinnati, Ohio, 45267, United States

Location

Options Health Research, LLC

Tulsa, Oklahoma, 74104, United States

Location

University Gastroenterology

Providence, Rhode Island, 02905, United States

Location

Memphis Gastroenterology Group

Germantown, Tennessee, 38138, United States

Location

Columbia Medical Group, The Frist Clinic

Nashville, Tennessee, 37203, United States

Location

Nashville Medical Research Institute

Nashville, Tennessee, 37205, United States

Location

Nashville Gastrointestinal Specialists, Inc

Nashville, Tennessee, 37211, United States

Location

The North Texas Research Institute

Arlington, Texas, 76012, United States

Location

Baylor University Medical Center

Dallas, Texas, 75246, United States

Location

Kelsey Research Foundation

Houston, Texas, 77005, United States

Location

Research Specialists of Texas

Houston, Texas, 77030, United States

Location

Metropolitan Research

Fairfax, Virginia, 22031, United States

Location

Digestive and Liver Disease Specialists

Norfolk, Virginia, 23502, United States

Location

Liver Institute of Virginia

Richmond, Virginia, 23249, United States

Location

Virginia Mason Medical Center, Digestive Disease Institute

Seattle, Washington, 98101, United States

Location

Fundacion de Investigacion de Diego

San Juan, 00927, Puerto Rico

Location

MeSH Terms

Conditions

Hepatitis C, ChronicHepatitis C

Interventions

ledipasvirGS-9451peginterferon alfa-2aRibavirin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepatitis, Viral, HumanVirus DiseasesFlaviviridae InfectionsRNA Virus InfectionsHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • Bittoo Kanwar, MD

    Gilead Sciences

    STUDY CHAIR

Study Design

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

Study Record Dates

First Submitted

June 9, 2011

First Posted

June 13, 2011

Study Start

July 1, 2011

Primary Completion

March 1, 2013

Study Completion

March 1, 2013

Last Updated

February 11, 2014

Record last verified: 2014-01

Locations