HCV InfectionPhase 2NCT00874796

Efficacy and Safety Study of GS-9450 Treatment for 6 Months in Patients With Chronic Hepatitis C Virus Infection

A Phase 2 study testing GS-9450 in people with HCV Infection, run by Gilead Sciences at 73 sites in 6 countries.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: HCV Infection
What is being tested?: GS-9450
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 307 participants
Where: 73 sitesin 6 countries
Study dates: May 2009to Jul 2010
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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Adult subjects, ages 18-65
Chronic HCV infection, defined as having documented HCV infection (antibody or RNA positivity) at least 6 months prior to Baseline (Day 1) with HCV viremia at screening
Screening Knodell necroinflammatory score >= 3 based on liver biopsy evaluation (as determined by local pathologist) conducted anytime during the 45-day screening period
ALT > the upper limit of the normal range (ULN) but < 10 X ULN at the screening visit
Previously failed pegylated interferon-based HCV therapy in combination with ribavirin therapy, or is unable to tolerate or has contraindications to receiving interferon or ribavirin therapy
BMI between 19 and 36 kg/m2 (inclusive)

Show all 10Show fewer

Creatinine clearance >= 70 mL/min
absolute neutrophil count >= 1000/mm3
Hemoglobin > 10 g/dL
Have no clinical or laboratory evidence of hepatic decompensation

Who cannot join

Decompensated liver disease
Child-Pugh grade B or C cirrhosis
Evidence of hepatocellular carcinoma
Positive urine drug screen for cocaine or amphetamines
Infection with HCV genotype 3
Co-infection with hepatitis B virus or human immunodeficiency virus

Show all 15Show fewer

Pancreatitis
Recent significant infection or symptoms of infection
Autoimmune disorders
Any history of seizure
Is a public transportation operator (pilot of airplane or ship; air traffic controller; bus, train or subway driver) or operates heavy construction machinery
Transplantation
History of malignancy
Current excessive alcohol ingestion, averaging > 3 drinks/day for females and > 4 drinks/day for males
History of or current binge drinking

Trial locations and contacts

73 sites in 6 countries.

Country

City, postcode or hospital

73 sites in 6 countries

United States51 sites

Study site
Anaheim, California
Study site
Annapolis, Maryland
Study site
Baltimore, Maryland
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Baton Rouge, Louisiana
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Beverly Hills, California
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Boston, Massachusetts
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Chattanooga, Tennessee
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Chicago, Illinois
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Cincinnati, Ohio
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Cleveland, Ohio
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Cypress, California
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Dallas, Texas
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Decatur, Georgia
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Fairfax, Virginia
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Falls Church, Virginia
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Germantown, Tennessee
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Hialeah, Florida
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Hillsborough, New Jersey
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Indianapolis, Indiana
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Johnson City, New York
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La Jolla, California
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Las Vegas, Nevada
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Louisville, Kentucky
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Madison, Wisconsin
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Miami, Florida
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Mission Hills, California
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Morristown, New Jersey
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New Orleans, Louisiana
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New York, New York
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Norfolk, Virginia
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North Miami Beach, Florida
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Novi, Michigan
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Omaha, Nebraska
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Orlando, Florida
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Palm Springs, California
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Pasadena, California
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Philadelphia, Pennsylvania
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Phoenix, Arizona
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Plainview, New York
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Plymouth, Minnesota
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Providence, Rhode Island
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Saint Louis, Michigan
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San Antonio, Texas
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San Clemente, California
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San Diego, California
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Santa Fe, New Mexico
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Sarasota, Florida
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Seattle, Washington
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Tampa, Florida
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Tucson, Arizona
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Washington D.C., District of Columbia

Other trials in United States

Germany8 sites

Study site
Berlin
Study site
Bonn
Study site
Cologne
Study site
Essen
Study site
Frankfurt am Main
Study site
Hamburg
Study site
Hanover
Study site
Mainz

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Poland5 sites

Study site
Bialystok
Study site
Bydgoszcz
Study site
Chorzów
Study site
Kielce
Study site
Wroclaw

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United Kingdom4 sites

Study site
Brighton
Study site
London
Study site
Nottingham
Study site
Sheffield

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Canada3 sites

Study site
London, Ontario
Study site
Vancouver, British Columbia
Study site
Winnipeg, Manitoba

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Puerto Rico2 sites

Study site
San Juan
Study site
Santurce

Other trials in Puerto Rico

About this study

Official title: A Phase 2b, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GS 9450 in Adults With Chronic Hepatitis C Virus Infection (GS-US-227-0106)

This is a Phase 2b, randomized, double-blind, parallel-group, placebo-controlled, multicenter study investigating the safety, tolerability and efficacy of two oral doses of GS-9450 in adults with chronic Hepatitis C Virus (HCV). Approximately 240 subjects 18-65 years of age who meet study entry criteria will be randomized (in other words, selected at random, like flipping a coin) to one of three treatment groups (80 subjects per treatment group) as follows:GS-9450 10 mg once daily,GS-9450 40 mg once daily, or matching placebo once daily.

Following randomization, subjects will return within seven business days for a Baseline (Day 1) visit, at which time study medication will be dispensed and subjects will enter a 26 week treatment phase. During the treatment phase, subjects will receive study drug once daily for 24 weeks and then taper off of study drug over the following 2 weeks by receiving study drug once every other day for one week and then every 3 days for one week. Following completion of the treatment phase, subjects will enter a 4-week off-treatment follow-up phase.

Conditions: HCV Infection
Being tested: GS-9450, Placebo
Keywords: apoptosis, liver inflammation, hepatitis C
Medical subject headings: Hepatitis C, Hepatitis

What participants receive

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

GS-9450Drug
Taken as one capsule by mouth once daily
PlaceboDrug
Taken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily

Study groups in NCT00874796
Study group	Role	What they receive
GS-9450 10 mg/day	Experimental	GS-9450 taken as one 10 mg capsule by mouth once daily Receives: Drug: GS-9450
GS-9450 40 mg/day	Experimental	GS-9450 taken as one 40 mg capsule by mouth once daily Receives: Drug: GS-9450
Placebo	Placebo comparator	Placebo taken as one placebo capsule by mouth once daily Receives: Drug: Placebo

What is being measured

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

Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
Measured: Week 24 on-treatment

Secondary outcomes (8)

Change (absolute, percent) from baseline in the Knodell necroinflammatory score
Measured: Baseline to Week 24
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
Measured: Baseline to Week 24
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Measured: Up to 24 weeks plus 30 days following the last dose of study drug
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
Measured: Baseline to Week 24
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
Measured: Baseline to Week 24
Change from baseline in the percent of apoptotic cells
Change from baseline in the percent of apoptotic cells (transferase deoxyuridine triphosphate [dUTP] nick end labeling [TUNEL] positive) as measured by TUNEL staining of liver biopsy specimens
Measured: Baseline to Week 24
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes (for cytokeratin-18 neoantigen expression) as measured by immunohistochemical staining of liver biopsy specimens
Measured: Baseline to Week 24
Change From Baseline in HCV RNA
Measured: Baseline to to Week 24

Timeline

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

May 2009Jul 2010

First posted3 Apr 2009 (estimated)
Study startMay 2009
Primary completionApr 2010
Study completionJul 2010

Why it stopped: Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HCV InfectionStudies of the same condition, open and under way.
More trials run by Gilead SciencesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

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: Non-randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 307 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00874796
Sponsor's protocol ID: GS-US-227-0106
Status last verified: Jan 2014
First submitted: 2 Apr 2009
Last updated: 4 Feb 2014
Results posted: No
Data monitoring committee: Yes

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 2b, Double-Blind, Randomized, Parallel-Group, Placebo-Controlled Study to Evaluate the Safety, Tolerability, and Efficacy of GS 9450 in Adults With Chronic Hepatitis C Virus Infection (GS-US-227-0106)
ClinicalTrials.gov ID: NCT00874796
Acronym / sponsor ID: GS-US-227-0106
Conditions: HCV Infection
Keywords: apoptosis, liver inflammation, hepatitis C
Phase: Phase 2
Study type: Interventional
Recruitment status: TerminatedReason stopped: Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.
Enrolment: 307 participants (actual)
Lead sponsor: Gilead SciencesIndustry (pharma, biotech, devices)
Study start: May 2009
Primary completion: Apr 2010 (actual)
Study completion: Jul 2010 (actual)
First posted: 3 Apr 2009 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Non-randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 3

Arm	Type	Receives
GS-9450 10 mg/day	Experimental	Drug: GS-9450GS-9450 taken as one 10 mg capsule by mouth once daily
GS-9450 40 mg/day	Experimental	Drug: GS-9450GS-9450 taken as one 40 mg capsule by mouth once daily
Placebo	Placebo comparator	Drug: PlaceboPlacebo taken as one placebo capsule by mouth once daily

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (10 listed)

Adult subjects, ages 18-65
Chronic HCV infection, defined as having documented HCV infection (antibody or RNA positivity) at least 6 months prior to Baseline (Day 1) with HCV viremia at screening
Screening Knodell necroinflammatory score >= 3 based on liver biopsy evaluation (as determined by local pathologist) conducted anytime during the 45-day screening period
ALT > the upper limit of the normal range (ULN) but < 10 X ULN at the screening visit
Previously failed pegylated interferon-based HCV therapy in combination with ribavirin therapy, or is unable to tolerate or has contraindications to receiving interferon or ribavirin therapy

Key exclusion criteria (15 listed)

Decompensated liver disease
Child-Pugh grade B or C cirrhosis
Evidence of hepatocellular carcinoma
Positive urine drug screen for cocaine or amphetamines
Infection with HCV genotype 3

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
GS-9450Taken as one capsule by mouth once daily	Drug	GS-9450 10 mg/day, GS-9450 40 mg/day
PlaceboTaken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily	Drug	Placebo

Primary outcome

Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 .
Time frame: Week 24 on-treatment

8 secondary outcomes

Change (absolute, percent) from baseline in the Knodell necroinflammatory score
Time frame: Baseline to Week 24
Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels
Time frame: Baseline to Week 24
Percentage of Participants Who Experienced Adverse Events (AEs) and Graded Laboratory Abnormalities
Time frame: Up to 24 weeks plus 30 days following the last dose of study drug
Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels
Time frame: Baseline to Week 24
Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens
Time frame: Baseline to Week 24
Change from baseline in the percent of apoptotic cells
Time frame: Baseline to Week 24
Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes
Time frame: Baseline to Week 24
Change From Baseline in HCV RNA
Time frame: Baseline to to Week 24

Results and safety

The study was stopped early (reason given: Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2014.

Related trials for HCV Infection

RecruitingObservational study
Evaluation of Patients With Liver Disease
Hepatitis D, Hepatitis C
Not yet recruiting
HIV/STI/HCV Testing and Overdose Prevention Among Survivors of Sex Trafficking
HIV Testing, STI
Not yet recruiting
Clinical Study to Evaluate the Performance of the INSTI® HCV Antibody Test for CLIA-Waived Use
HCV Infection
Not yet recruiting
Study to Evaluate the Performance of the INSTI® HCV Antibody Test for Point-of-Care Use in Individuals at Risk for HCV Infection or Presenting With Signs or Symptoms of HCV Infection
HCV Infection
Recruiting
HIV/HBV/HCV Triple Screening in Primary Care
HIV, HBV (Hepatitis B Virus)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Ken Hirsch, MD study director

Gilead Sciences

73 sites in 6 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing GS-9450 in people with HCV Infection, run by Gilead Sciences at 73 sites in 6 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 10 inclusion and 15 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: stopped early, as of the sponsor's last update on 4 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 73 sites in United States, Germany, Poland, United Kingdom, Canada and 1 more country. 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?

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?

Histologic response, defined as a >= 2-point decrease in Knodell necroinflammatory score with no concurrent worsening in the Knodell fibrosis score, at Week 24 . (time frame: Week 24 on-treatment). 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 NCT00874796.

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 4 Feb 2014.