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Hepatitis C, ChronicPhase 2NCT01371578

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

A Phase 2 study testing GS-5885 tablet, GS-9451 tablet and peginterferon alfa-2a in people with Hepatitis C, Chronic, run by Gilead Sciences at 55 sites in 2 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 80 years
Conditions the study is for
Hepatitis C, Chronic
What is being tested?
GS-5885 tablet, GS-9451 tablet and peginterferon alfa-2a
Could I receive a placebo?
No, everyone receives an active treatment
How many people
163 participants
Where
55 sitesin 2 countries
Study dates
Jul 2011to Mar 2013
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 80 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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.

Trial locations and contacts

55 sites in 2 countries.

55 sites in 2 countries

United States54 sites

  • The North Texas Research Institute

    Arlington, Texas, 76012

  • Asheville Gastroenterology Associates, P.A.

    Asheville, North Carolina, 28801

  • Emory University, Infectious Disease Clinic

    Atlanta, Georgia, 30308

  • Digestive Healthcare of Georgia

    Atlanta, Georgia, 30309

  • University of Colorado Denver

    Aurora, Colorado, 80045

  • Digestive Disease Associates, PA

    Baltimore, Maryland, 21229

  • Gastroenterology Associates, LLC

    Baton Rouge, Louisiana, 70809

  • California Liver Institute

    Beverly Hills, California, 90211

  • Binghamton Gastroenterology

    Binghamton, New York, 13903

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02115

  • Graves Gilbert Clinic

    Bowling Green, Kentucky, 42101

  • Bach and Godofsky Infectious Diseases

    Bradenton, Florida, 34209

  • University of Cincinnati

    Cincinnati, Ohio, 45267

  • Baylor University Medical Center

    Dallas, Texas, 75246

  • Dekalb Gastroenterology

    Decatur, Georgia, 30033

  • Henry Ford Health System

    Detroit, Michigan, 48202

  • Digestive Health Specialists of the Southeast

    Dothan, Alabama, 36305

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • South Denver Gastroenterology

    Englewood, Colorado, 80110

  • Metropolitan Research

    Fairfax, Virginia, 22031

  • Cumberland Research Associates, LLC

    Fayetteville, North Carolina, 28304

  • University of Florida

    Gainesville, Florida, 32610

  • Memphis Gastroenterology Group

    Germantown, Tennessee, 38138

  • ID Care 105

    Hillsborough, New Jersey, 08844

  • Kelsey Research Foundation

    Houston, Texas, 77005

  • Research Specialists of Texas

    Houston, Texas, 77030

  • Indiana University

    Indianapolis, Indiana, 46202

  • Indianapolis Gastroenterology Research Foundation

    Indianapolis, Indiana, 46237

  • Gastrointestinal Associates, PA

    Jackson, Mississippi, 39202

  • Scripps Clinic

    La Jolla, California, 92037

  • North Shore University Hospital

    Manhasset, New York, 11030

  • Gastrointestinal Specialists of Georgia PC

    Marietta, Georgia, 30060

  • University of Miami

    Miami, Florida, 33136

  • Alabama Liver and Digestive Specialists

    Montgomery, Alabama, 36116

  • Atlantic Research Affiliates, LLC

    Morristown, New Jersey, 07960

  • Columbia Medical Group, The Frist Clinic

    Nashville, Tennessee, 37203

  • Nashville Medical Research Institute

    Nashville, Tennessee, 37205

  • Nashville Gastrointestinal Specialists, Inc

    Nashville, Tennessee, 37211

  • Concorde Medical Group

    New York, New York, 10016

  • Cornell University Gastroenterology & Hepatology

    New York, New York, 10021

  • Digestive and Liver Disease Specialists

    Norfolk, Virginia, 23502

  • Orlando Immunology Center

    Orlando, Florida, 32803

  • University Gastroenterology

    Providence, Rhode Island, 02905

  • Liver Institute of Virginia

    Richmond, Virginia, 23249

  • University of California Davis Medical Center

    Sacramento, California, 95817

  • RESEARCH and EDUCATION, INC

    San Diego, California, 92015

  • Medical Associates Research Group

    San Diego, California, 92123

  • Kaiser Permanente

    San Diego, California, 92154

  • Southwest CARE Center

    Santa Fe, New Mexico, 87505

  • Virginia Mason Medical Center, Digestive Disease Institute

    Seattle, Washington, 98101

  • Options Health Research, LLC

    Tulsa, Oklahoma, 74104

  • Digestive Health Specialists, PA

    Tupelo, Mississippi, 38801

  • South Florida Center of Gastroenterology, LLC

    Wellington, Florida, 33414

  • Partners in Internal Medicine, P.C.

    Worcester, Massachusetts, 01608

Other trials in United States

Puerto Rico1 site

  • Fundacion de Investigacion de Diego

    San Juan, 00927

Other trials in Puerto Rico

About this study

Official title: 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 Infection (Protocol GS US 256 0124)

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.

Read the detailed description

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.

Being tested
GS-5885 tablet, GS-9451 tablet, peginterferon alfa-2a, ribavirin tablet
Keywords
Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, Direct Acting Antiviral, Combination Therapy HCV RNA, Polymerase inhibitor, Protease inhibitor, Treatment naïve, GS-5885, GS-9190, Tegobuvir, GS-9451
Medical subject headings
Hepatitis C, Chronic, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GS-5885 tabletDrug

    30 mg active tablet

  • GS-9451 tabletDrug

    two active 100 mg tablets

  • peginterferon alfa-2aBiological

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

  • ribavirin tabletDrug

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

Study groups in NCT01371578
Study groupRoleWhat they receive
Arm 2ExperimentalAM 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.
Receives: Drug: GS-5885 tablet; Drug: GS-9451 tablet; Biological: peginterferon alfa-2a; Drug: ribavirin tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: through 24 weeks of off-treatment follow-up

Secondary outcomes (5)

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

    To evaluate antiviral efficacy as measured by SVR for 24 or 48 weeks of treatment with GS-5885, GS-9451, PEG, RBV.

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

  2. Safety and Tolerability

    To evaluate the safety and tolerability of treatment with GS-5885, GS-9451, PEG \& RBV administered for 24 or 48 weeks. Safety endpoints will be summarized as the number (proportion) of subjects with events or abnormalities for categorical values or as an 8-number summary (n, mean, standard deviation, median, Q1, Q3, minimum, maximum) for continuous data by treatment arm.

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

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

    HCV RNA levels, pharmacokinetics, and viral sequencing

    Measured: Through Week 2 of therapy

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

    Plasma concentrations of the study drug over time will be summarized using descriptive statistics. Pharmacokinetic parameters (Cmax, Tmax, Clast, Tlast, Ctau, λz, AUCtau, and T½) will be listed and summarized for GS-5885 and GS-9451, using descriptive statistics (eg, sample size, arithmetic mean, geometric mean, % coefficient of variation, standard deviation, median, minimum, and maximum).

    Measured: Through Week 2 of therapy

  5. Emergence of Viral Resistance

    To characterize the viral resistance to GS-5885 and GS 9451tegobuvir when administered in combination with PEG and RBV.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Jun 2011 (estimated)
  2. Study startJul 2011
  3. Primary completionMar 2013
  4. Study completionMar 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
163 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01371578
Sponsor's protocol ID
GS-US-256-0124
Status last verified
Jan 2014
First submitted
9 Jun 2011
Last updated
11 Feb 2014
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GS-5885 tablet, GS-9451 tablet and peginterferon alfa-2a in people with Hepatitis C, Chronic, run by Gilead Sciences at 55 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 55 sites in United States, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Sustained Virologic Response (SVR) (time frame: through 24 weeks of off-treatment follow-up). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01371578.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Feb 2014.

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