GS 5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) in Chronic Genotype 1 Hepatitis C Virus (HCV) Infection

A Phase 2 Randomized, Open-Label Study of GS-5885 Administered Concomitantly With GS-9451, Tegobuvir and Ribavirin (RBV) to Treatment-Naive Subjects With Chronic Genotype 1 HCV Infection

The purpose of this phase 2 study is to determine whether 30 mg or 90 mg of GS-5885 when given with GS-9451, Tegobuvir and Ribavirin (RBV) for 12 or 24 weeks is effective, safe and tolerable in the treatment of Chronic Genotype 1 HCV Infection.

Study Overview

• Status: Completed
• Conditions: Hepatitis C, Chronic
• Intervention / Treatment: Drug: GS-5885; Drug: GS-9451; Drug: Tegobuvir; Drug: ribavirin tablet; Drug: GS-5885

• Study Type: Interventional
• Enrollment (Actual): 141
• Phase: Phase 2

Contacts and Locations

Study Locations

• Puerto Rico
  • San Juan, Puerto Rico, 00927
    • Fundacion de Investigacion de Diego
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35209
      • Birmingham Gastroenterology Associates, P.C.
    • Dothan, Alabama, United States, 36305
      • Digestive Health Specialists of the Southeast
  • California
    • Anaheim, California, United States, 92801
      • Advanced Clinical Research Institute
    • Coronado, California, United States, 92118
      • Southern California Liver Centers
    • Fresno, California, United States, 93721
      • UCSF Fresno Medical Education Program (MEP)
    • Palo Alto, California, United States, 94304
      • Stanford University School of Medicine
    • San Diego, California, United States, 92103
      • University of California San Diego
    • San Diego, California, United States, 92154
      • Kaiser Permanente
    • San Francisco, California, United States, 94143
      • UCSF
  • District of Columbia
    • Washington, District of Columbia, United States, 20307
      • Walter Reed Army Medical Center
  • Florida
    • Bradenton, Florida, United States, 34209
      • Bach and Godofsky Infectious Diseases
    • Gainesville, Florida, United States, 32610
      • University of Florida - Gainesville
    • Jacksonville, Florida, United States, 32256
      • Borland-Groover Clinic
    • Miami, Florida, United States, 33136
      • University of Miami School of Medicine
    • Orlando, Florida, United States, 32809
      • Orlando Clinical Research Center
    • Orlando, Florida, United States, 32803
      • Orlando Immunology Center
  • Georgia
    • Marietta, Georgia, United States, 30060
      • Gastrointestinal Specialists of Georgia PC
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Louisiana
    • Opelousas, Louisiana, United States, 70570
      • Private Practice
  • Maryland
    • Lutherville, Maryland, United States, 21093
      • Johns Hopkins University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
    • Boston, Massachusetts, United States, 02115
      • Beth Israel Deaconess Medical Center
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Gastrointestinal Associates, PA
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
      • University of New Mexico
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai Medical Center
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599-7584
      • University of North Carolina At Chapel Hill
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic
  • Oklahoma
    • Tulsa, Oklahoma, United States, 74104
      • Options Health Research, LLC
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania Hospital
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • Gastro One
    • Germantown, Tennessee, United States, 38138
      • Memphis Gastroenterology Group
    • Nashville, Tennessee, United States, 37211
      • Nashville Gastrointestinal Specialists, Inc
    • Nashville, Tennessee, United States, 37203
      • Columbia Medical Group, The Frist Clinic
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center
    • Houston, Texas, United States, 77030
      • Research Specialists of Texas
    • San Antonio, Texas, United States, 78215
      • Alamo Medical Research
  • Utah
    • Salt Lake City, Utah, United States, 84106
      • Lifetree Clinical Research, LC
  • Virginia
    • Falls Church, Virginia, United States, 22042
      • Inova Fairfax Hospital - Center for Liver Diseases
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia, Bon Secours Health System

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adult subjects 18 to 70 years of age
• Chronic HCV infection for at least 6 months prior to Baseline (Day 1)
• Liver biopsy results (performed no more than 2 years prior to Screening) indicating the absence of cirrhosis
• Monoinfection with HCV genotype 1a or 1b
• HCV treatment-naïve
• Body mass index (BMI) between 18 and 36 kg/m2
• Creatinine clearance ≥ 50 mL/min
• Subject agrees to use highly effective contraception methods if female of childbearing potential or sexually active male.
• Screening laboratory values within defined thresholds

Exclusion Criteria:

• Autoimmune disease
• Decompensated liver disease or cirrhosis
• Poorly controlled diabetes mellitus
• Severe psychiatric illness
• Severe chronic obstructive pulmonary disease (COPD)
• Serological evidence of co-infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), or another HCV genotype
• Suspicion of hepatocellular carcinoma or other malignancy (with exception of certain skin cancers)
• History of hemoglobinopathy
• Known retinal disease
• Subjects who are immunosuppressed
• Subjects with known, current use of amphetamines, cocaine, opiates (i.e., morphine, heroin), methadone, or ongoing alcohol abuse
• Subjects must have no history of clinically significant cardiac disease, including a family history of Long QT syndrome, and no relevant electrocardiogram (ECG) abnormalities at screening

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm 1; GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 24 weeks.	Drug: GS-5885; tablet, 30 mg QD; Drug: GS-9451; tablet, 200 mg QD; Drug: Tegobuvir; capsule, 30 mg BID; Drug: ribavirin tablet; (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); Drug: GS-5885; tablet, 90 mg QD
Active Comparator: Arm 2; GS-5885, GS-9451 and Tegobuvir in combination with ribavirin (Copegus®) for 12 or 24 weeks.	Drug: GS-5885; tablet, 30 mg QD; Drug: GS-9451; tablet, 200 mg QD; Drug: Tegobuvir; capsule, 30 mg BID; Drug: ribavirin tablet; (weight based: 1000 mg/day <75 kg; 1200 mg/day ≥ 75 kg) divided twice daily (BID); Drug: GS-5885; tablet, 90 mg QD

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Sustained virologic response (SVR)	24 weeks of off-treatment follow-up

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability	To evaluate the safety and tolerability of 30 mg or 90 mg GS-5885 when given with GS-9451, Tegobuvir and RBV for 12 or 24 weeks. Safety endpoints will be analyzed by the number and percent of subjects with events or abnormalities for categorical values or 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment group.	through 24 weeks of off-treatment follow-up
HCV RNA < Lower Limit Of Quantification	To evaluate the antiviral efficacy at Weeks 1, 2, 4, 12 and 24, as measured by the rates of HCV RNA < LLoQ and viral breakthrough and relapse.	Weeks 1, 2, 4, 12 and 24
Rescue Therapy Substudy SVR	To evaluate the antiviral efficacy (as defined by SVR) of the addition of pegylated interferon (PEG) for 24 weeks to GS-5885, GS-9451, tegobuvir and RBV in subjects who experience viral breakthrough on treatment.	24 Weeks
Emergence of viral resistance	To evaluate the emergence of viral resistance during treatment with GS-9451, Tegobuvir and RBV when given with 30 mg or 90 mg GS-5885 for 12 or 24 weeks.	12 or 24 weeks
Viral dynamics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV	HCV RNA levels, pharmacokinetics and viral sequencing	Through Week 2 of therapy
Pharmacokinetics of GS-5885, GS-9451 and Tegobuvir when administered in combination with RBV	Pharmacokinetics (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885, GS-9451 and Tegobuvir using descriptive statistics (e.g., sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum). Plasma concentrations of the study drug over time will be summarized using descriptive statistics	Through Week 2 of therapy

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Benedetta Massetto, MD, PhD, Gilead Sciences

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Actual): October 1, 2012
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: April 22, 2011
• First Submitted That Met QC Criteria: May 11, 2011
• First Posted (Estimate): May 13, 2011

Study Record Updates

• Last Update Posted (Estimate): December 20, 2013
• Last Update Submitted That Met QC Criteria: November 26, 2013
• Last Verified: November 1, 2013

More Information

Terms related to this study

• Keywords: HCV; Sustained Virologic Response; Hepatitis C; Combination Therapy; Protease inhibitor; Direct Acting Antiviral; GS-5885; Rapid Virologic Response; Tegobuvir; HCV RNA; Polymerase inhibitor; GS-9451; Treatment naïve
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis; Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Ribavirin; Ledipasvir
• Other Study ID Numbers: GS-US-248-0120