AzTrials
AzTrials

HCV InfectionPhase 2NCT00743795

Safety, Tolerability, and Antiviral Activity of 24 or 48 Weeks of GS-9190 in Combination With Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection

A Phase 2 study testing GS-9190, Peginterferon Alfa 2a and Ribavirin in people with HCV Infection, run by Gilead Sciences at 72 sites in 7 countries.

Completed

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

Official record
Search all trials

Trial summary

The purpose of this study is to compare the safety, tolerability and effectiveness of the experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and ribavirin for the treatment of genotype-1 chronic hepatitis C infection. Read more about this study

Who is it for?
Ages 18 to 70 years
Conditions the study is for
HCV Infection
What is being tested?
GS-9190, Peginterferon Alfa 2a and Ribavirin
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
252 participants
Where
72 sitesin 7 countries
Study dates
Oct 2008to Sep 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 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adult subjects (18 - 70 years of age)
  • Chronic HCV infection for at least 6 months prior to Baseline (Day 1) (anti-HCV antibody positive; positive for plasma HCV RNA; medical history consistent with chronicity accepted by the investigator)
  • Liver biopsy results within the past 2 years prior to Baseline (Day 1) indicating the absence of cirrhosis
  • HCV treatment-naive, defined as no prior exposure to PEG, RIBA, or experimental HCV therapy
  • Mono-infection with HCV genotype 1a or 1b
  • Detectable plasma HCV RNA at Screening
Show all 15Show fewer
  • BMI between 19 and 36 kg/m2
  • Willing and able to provide written informed consent and to comply with all study requirements
  • Of generally good health as determined by the Investigator
  • Subject agrees to use adequate skin protection (e.g., sunblocking agent) when exposed to the sun.
  • Women of childbearing potential (i.e., a non-menopausal female or a female with menopausal < 2 years, who has not had a hysterectomy, bilateral oophorectomy or medically documented ovarian failure) must have negative serum β-human chorionic gonadotropin (hCG) at screening and negative urine pregnancy test prior to the first study drug administration.
  • All subjects (male and female) must agree to utilize highly effective contraception methods (two separate forms of contraception, one of which must be an effective barrier method, or be non-heterosexually active, practice sexual abstinence or have a vasectomized partner) from screening throughout the duration of study treatment and for 24 weeks after the last dose of RIBA.
  • Female subjects who utilize hormonal contraceptive as one of their birth control methods must have used the same method for at least three months prior to study dosing.
  • Female subjects who are postmenopausal for less than two years are required to have FSH > 40 mIU/mL. If the FSH is ≤ 40 mIU/mL, the subject must agree to use highly effective method of birth control (as described above) to participate in the study.
  • Male subjects who are sexually active must be willing to use effective barrier contraception (e.g., condom with spermicide) during heterosexual intercourse from screening through completion of the study and continue for 24 weeks after the last dose of RIBA

Who cannot join

  • Pregnant or breast feeding women or women who may wish to become pregnant during the course of the study
  • Males who have partners planning to become pregnant
  • Males and females of reproductive potential who are unwilling to use two forms of effective birth control through Study Week 72. One method should include a condom with spermicide for males
  • Infection with non-genotype 1 HCV
  • Poorly controlled diabetes mellitus (hemoglobin A1c > 7) unless treatment intervention has been reviewed with the Medical Monitor and improved glucose control is anticipated
  • History of sarcoidosis
Show all 23Show fewer
  • History of hemoglobinopathy (e.g., thalassemia)
  • History of known retinal disease
  • History of invasive malignancy diagnosed or treated within 5 years (recent localized treatment of squamous or non-invasive basal cell skin cancers is permitted; cervical carcinoma in situ is allowed if appropriately treated prior to screen)
  • Evidence of hepatocellular carcinoma
  • Chronic liver disease of a non-HCV etiology
  • Untreated or significant psychiatric illnesses including severe depression, schizophrenia, psychosis, or a history of a suicide attempt
  • Co-infection with HIV, HBV, or multiple HCV genotypes
  • Chronic use of systemic immunosuppressive agents
  • Presence of autoimmune disorders. Subjects with treated hypothyroidism with normal TSH may be enrolled.
  • Severe chronic obstructive pulmonary disease
  • History of clinically significant cardiac disease, including a family history of Long QT Syndrome, and/or evidence of the following ECG abnormalities at screening: QTcF (QT corrected using Fridericia's formula) of > 450 msec; complete or incomplete left or right bundle branch block; intraventricular conduction delay with QRS duration of > 120 msec; bradycardia (< 45 beats per minute); pathologic Q-waves (Q wave of > 40 msec or depth of > 0.4 to 0.5 V); arrhythmia (an isolated premature ventricular contraction on screening/Day 1 is not exclusionary) ; ventricular pre excitation; second or third degree heart block
  • Positive urine screen for amphetamines or cocaine
  • Known, current heroin, morphine, or methadone use
  • Ongoing alcohol abuse in the judgment of the investigator (in no case intake of more than 28 units of alcohol per week [1 unit = ½ pint of beer, 1 glass of wine, 1 shot of spirits])
  • Receiving a known potent CYP 3A4 inhibitor within 2 weeks of study drug dosing or are expected to receive such therapy during the course of study drug dosing
  • Known hypersensitivity to the study drugs, their metabolites or formulation excipients
  • In the judgment of the Investigator, should not participate in the study due to potential clinical or compliance issues

Trial locations and contacts

72 sites in 7 countries.

72 sites in 7 countries

United States48 sites

  • Study site

    Anaheim, California, 92801

  • Study site

    Annandale, Virginia, 22003-6800

  • Study site

    Asheville, North Carolina, 28801

  • Study site

    Atlanta, Georgia, 30308

  • Study site

    Baltimore, Maryland, 21201

  • Study site

    Baltimore, Maryland, 21229

  • Study site

    Baltimore, Maryland, 21287

  • Study site

    Baton Rouge, Louisiana, 70809

  • Study site

    Boston, Massachusetts, 02114

  • Study site

    Bowling Green, Kentucky, 42101

  • Study site

    Cedar Knolls, New Jersey, 07927

  • Study site

    Chicago, Illinois, 60611

  • Study site

    Cincinnati, Ohio, 45219

  • Study site

    Cincinnati, Ohio, 45267

  • Study site

    Dallas, Texas, 75208

  • Study site

    Decatur, Georgia, 30033

  • Study site

    Detroit, Michigan, 48202

  • Study site

    Durham, North Carolina, 27710

  • Study site

    Englewood, Colorado, 80110

  • Study site

    Fairfax, Virginia, 22031

  • Study site

    Germantown, Tennessee, 38138

  • Study site

    High Point, North Carolina, 27262

  • Study site

    Houston, Texas, 77090

  • Study site

    Johnson City, New York, 13790

  • Study site

    Los Angeles, California, 90048

  • Study site

    Miami, Florida, 33136

  • Study site

    New York, New York, 10016

  • Study site

    New York, New York, 10021

  • Study site

    New York, New York, 10029-6574

  • Study site

    New York, New York, 10032

  • Study site

    Newport Beach, California, 92663

  • Study site

    Norfolk, Virginia, 23502-3927

  • Study site

    North Miami Beach, Florida, 33162

  • Study site

    Orlando, Florida, 32803

  • Study site

    Philadelphia, Pennsylvania, 19104

  • Study site

    Philadelphia, Pennsylvania, 19140

  • Study site

    Plainview, New York, 11803

  • Study site

    Richmond, Virginia, 23298

  • Study site

    San Antonio, Texas, 78215

  • Study site

    San Clemente, California, 92673

  • Study site

    San Diego, California, 92115

  • Study site

    San Diego, California, 92123

  • Study site

    San Francisco, California, 94115

  • Study site

    Sarasota, Florida, 34243

  • Study site

    St Louis, Missouri, 63104

  • Study site

    Syracuse, New York, 13210

  • Study site

    Tampa, Florida, 33613

  • Study site

    Tulsa, Oklahoma, 74104

Other trials in United States

Germany6 sites

  • Study site

    Berlin, 10969

  • Study site

    Cologne, 50921

  • Study site

    Frankfurt, 60590

  • Study site

    Hamburg, 20099

  • Study site

    Hanover, 30625

  • Study site

    München, 80336

Other trials in Germany

Poland6 sites

  • Study site

    Bialystok, 15-540

  • Study site

    Bydgoszcz, 85-030

  • Study site

    Chorzów

  • Study site

    Czeladź, 41-250

  • Study site

    Krakow, 31-501

  • Study site

    Warsaw, 01-201

Other trials in Poland

Belgium5 sites

  • Study site

    Brussels, B-1070

  • Study site

    Brussels, B-1200

  • Study site

    Ghent, B-9000

  • Study site

    Leuven

  • Study site

    Liège

Other trials in Belgium

Ireland3 sites

  • Study site

    Dublin, 8

  • Study site

    Dublin, 9

  • Study site

    Dublin

Other trials in Ireland

United Kingdom3 sites

  • Study site

    Birmingham, B15 2TH

  • Study site

    London, E1 1BB

  • Study site

    London

Other trials in United Kingdom

Puerto Rico1 site

  • Study site

    Santurce, 00909

Other trials in Puerto Rico

About this study

Official title: A Phase 2b, Randomized, Double-Blind, Placebo-Controlled Trial Comparing 24 or 48 Weeks of GS 9190, in Combination With Peginterferon Alfa 2a and Ribavirin, to 48 Weeks of Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic Hepatitis C Virus (HCV) Infection (GS-US-196-0103)

The purpose of this study is to compare the safety, tolerability and effectiveness of the experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and ribavirin for the treatment of genotype-1 chronic hepatitis C infection.

Read the detailed description

The safety, tolerability and antiviral efficacy GS-9190, administered orally twice daily at 40 mg, will be compared to placebo when used in combination with peginterferon alfa 2a (PEG) and ribavirin (RIBA) in treatment-naïve subjects chronically infected with HCV genotype 1 infection. Two-hundred forty-eight (248) subjects will be randomized (ratio: 1:2:1) to one of three treatment arms:

Arm 1: PEG/RIBA + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 62)

Arm 2: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 124)

Arm 3: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 62).

Randomization will be stratified by plasma HCV RNA level (< or ≥ 400,000 IU/mL) at screening and race (of African descent or other).

In order to ensure adequate representation of subjects with genotypes 1a and 1b in this trial, enrollment for either genotype will be capped at 120 subjects. Once 120 subjects of either genotype (e.g., genotype 1a) have been randomized, subsequent enrollment will only be allowed for subjects with the other genotype (e.g., genotype 1b).

The duration of double-blind treatment is 48 weeks plus 24 weeks of treatment-free follow-up; however subjects in Arm 3 will stop all medication at Week 24 if they have achieved an RVR (defined by undetectable HCV RNA following 4 weeks on therapy) and have maintained that response thereafter. Subjects will only learn that they have been randomized to Arm 3 if, at Week 24, having achieved criteria for stopping therapy, they are instructed to stop. All other subjects will remain blinded to their treatment status throughout the course of the study.

The standard of care treatment stopping criterion used in clinical practice when treating HCV with PEG/RIBA, failure to achieve EVR, will be utilized in this trial. Additionally, subjects with detectable plasma HCV RNA at Week 24 will discontinue all study medications no later than the Week 28 visit and will be followed off-treatment for 24 weeks.

Conditions
HCV Infection
Being tested
placebo, GS-9190, Peginterferon Alfa 2a, Ribavirin
Keywords
Hepatitis C, HCV, Rapid Virologic Response, Sustained Virologic Response, HCV RNA, Polymerase inhibitor, GS-9190
Medical subject headings
Hepatitis C

What participants receive

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

  • placeboDrug

    oral BID

  • GS-9190Drug

    40 mg oral BID

  • Peginterferon Alfa 2aDrug

    Also called PEG

    All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.

  • RibavirinDrug

    Also called RBV

    Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.

Study groups in NCT00743795
Study groupRoleWhat they receive
1Placebo comparatorPeginterferon and ribavirin + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 50)
Receives: Drug: placebo; Drug: Peginterferon Alfa 2a; Drug: Ribavirin
2ExperimentalPeginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n = 100)
Receives: Drug: GS-9190; Drug: Peginterferon Alfa 2a; Drug: Ribavirin
3ExperimentalPeginterferon and ribavirin + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up. However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48 weeks (n = 50).
Receives: Drug: GS-9190; Drug: Peginterferon Alfa 2a; Drug: Ribavirin

What is being measured

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

  1. Undetectable HCV RNA level

    Measured: At Week 12 for Early Virologic Response (EVR)

Secondary outcomes (4)

  1. Safety and tolerability

    Measured: Throughout 72 week study period

  2. Undetectable HCV RNA level

    Measured: Week 4, Week 24 and Week 48

  3. GS-9190 plasma concentrations

    Measured: Through Week 48

  4. Undetectable HCV RNA

    Measured: At Week 72 for sustained virologic response (SVR)

Timeline

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

  1. First posted29 Aug 2008 (estimated)
  2. Study startOct 2008
  3. Primary completionJul 2009
  4. Study completionSep 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
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
252 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00743795
Sponsor's protocol ID
GS-US-196-0103
Status last verified
Oct 2013
First submitted
27 Aug 2008
Last updated
5 Nov 2013
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GS-9190, Peginterferon Alfa 2a and Ribavirin in people with HCV Infection, run by Gilead Sciences at 72 sites in 7 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 15 inclusion and 23 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 5 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 72 sites in United States, Germany, Poland, Belgium, Ireland and 2 more countries. 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. Some participants in this study may receive a placebo. 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?

Undetectable HCV RNA level (time frame: At Week 12 for Early Virologic Response (EVR)). 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 NCT00743795.

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 5 Nov 2013.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in