HCV InfectionPhase 2NCT00725803
Evaluation of the Safety, Tolerability, Pharmacokinetics, and Activity of GS-9450 in Subjects With Chronic HCV
A Phase 2 study testing GS-9450 in people with HCV Infection, run by Gilead Sciences at 11 sites in 3 countries.
Trial summary
The purpose of this study is to examine the safety, tolerability, pharmacokinetics (studies how the body processes a drug), and initial activity of GS-9450 in preventing liver damage due to scarring, or fibrosis, caused by Hepatitis C Virus (HCV) infection. Read more about this study
- 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
- 33 participants
- Where
- 11 sitesin 3 countries
- Study dates
- Apr 2008to Mar 2009
- 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
- Male or female, aged from 18 to 65 years old, inclusive.
- Willing and able to provide written, informed consent
- Have a body mass index between 19 and 32 kg/m2, inclusive, at screening.
- Have chronic hepatitis C infection of any genotype (and subtype).
- Subjects must be previously treated with pegylated interferon (PEG) or interferon (INF) with or without ribavirin (RBV) and either did not achieve a sustained viral response (undetectable HCV RNA) six months after cessation of anti-viral therapy, or did not tolerate PEG or INF with or without RBV therapy. Subjects who have contraindications to receiving PEG or INF with or without RBV may also be eligible.
- ALT >/= 1.5 X but < 10 X the upper limit of the normal range (ULN); aspartate aminotransferase (AST) < 10 X ULN; platelets >/= 75,000/mm3; total bilirubin </= 1.5 X ULN; prothrombin time </= 1.5 X ULN; albumin >/= 3.0 g/dL; absolute neutrophil count >/= 1,000 cells/mm3; and hemoglobin >/= 10 g/dL
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- Creatinine clearance >/= 70 mL/min
- A female of non-childbearing potential who is documented as either surgically sterile or post-menopausal for >/= 2 years.
- Females < 2 years post-menopausal are required to have follicle-stimulating hormone (FSH) level of >/= 40 mIU/mL. If of child-bearing potential or FSH < 40 mIU/mL, must:
- have negative serum pregnancy test and a negative urine pregnancy test, and
- agree to use an acceptable method of contraception during heterosexual intercourse during the study and for >/= 30 days or one menstrual cycle (whichever is the longer) after last dose of study drug.
- If male, agree to use an acceptable method of contraception during heterosexual intercourse during the study and for at least 3 months after the last dose of study drug.
- Subjects should be in reasonably good health as determined by the Investigator.
Who cannot join
- Pregnant or breast feeding women or women who may wish to become pregnant during the study or within 30 days of study drug administration.
- Males who have partners planning to become pregnant within 30 days of study drug administration.
- Males and females of reproductive potential who are unwilling to use effective method(s) of birth control for a minimum of 30 days after ingestion of study medication
- Coinfection with hepatitis B virus (HBV) or HIV
- Known liver disease of a non-HCV etiology
- Pancreatitis
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- Autoimmune disease
- History of malignancy
- Ongoing alcohol abuse.
- Recent significant infection or symptoms of infection
- Evidence of hepatocellular carcinoma (e.g., a-fetoprotein > 50 ng/mL or as indicated by recent ultrasound)
- Decompensated liver disease OR history of clinical hepatic decompensation
- Hb < 10 g/dL
- Absolute neutrophil count (ANC) < 1,000 cells/mm3
- Therapy with potentially hepatotoxic/cholestatic drugs.
- Therapy with agents having potential hepatic anti-inflammatory or anti-fibrotic properties.
- Therapy with proton pump inhibitors or histamine-2 receptor antagonists.
- Have received therapy with systemic steroids, immunosuppressant therapies or chemotherapeutic agents within 90 days prior to Day 1 or are expected to receive such therapy during the study.
- With or a history of clinically significant illness or medical disorder that may interfere with treatment, assessment or compliance.
- Have a history of a primary gastrointestinal disorder that could interfere with the absorption of the study drug or that could interfere with normal gastrointestinal anatomy or motility.
- Received study medication while participating in another research study within 60 days prior to Day 1.
- A positive urine drug screen
- Known hypersensitivity to the study drugs, the metabolites or formulation excipients.
- Known aspirin allergy.
Trial locations and contacts
11 sites in 3 countries.
11 sites in 3 countries
United States5 sites
Study site
Anaheim, California
Study site
Dallas, Texas
Study site
Orlando, Florida
Study site
San Antonio, Texas
Study site
Washington D.C., District of Columbia
Germany5 sites
Study site
Frankfurt
Study site
Hamburg
Study site
Hanover
Study site
Mainz
Study site
Würzburg
About this study
Official title: A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Activity of GS-9450, a Caspase Inhibitor, in Subjects With Chronic Hepatitis C (GS-US-227-0102)
The purpose of this study is to examine the safety, tolerability, pharmacokinetics (studies how the body processes a drug), and initial activity of GS-9450 in preventing liver damage due to scarring, or fibrosis, caused by Hepatitis C Virus (HCV) infection.
Read the detailed description
Approximately 32 subjects will receive GS 9450 or placebo for 14 consecutive days. Eight subjects will receive treatment within each of four dosing cohorts; 6 randomized to receive GS 9450 and two randomized to placebo:
Cohort 1: GS 9450 10 mg or placebo given daily x 14 days Cohort 2: GS 9450 40 mg or placebo given daily x 14 days Cohort 3: GS 9450 80 mg or placebo given daily x 14 days
If further characterization of the activity profile is deemed necessary, an additional cohort at a lower dose (5 mg) may be enrolled:
Cohort 4: GS 9450 5 mg or placebo given daily x 14 days
Each cohort will be conducted sequentially. Advancement to higher dose cohorts is dependent upon satisfactory safety and tolerability profiles of the preceding cohort as determined by Sponsor review (conducted in consultation with the Lead Investigator[s]). Progression to Cohort 4 (5 mg dose strength) will not require a safety review of Cohort 3 (80 mg dose strength); screening and randomization for Cohort 4 may begin immediately after fully enrolling Cohort 3. Alternatively, if a dose-response relationship is apparent in review of the blinded activity data from the first three cohorts, the final 5 mg cohort may be omitted.
- Conditions
- HCV Infection
- Being tested
- GS-9450, GS-9450 Placebo
- Keywords
- Hepatitis C, HCV, Fibrosis, Apoptosis, GS-9450
- Medical subject headings
- Hepatitis C, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-9450Drug
GS-9450 capsules administered orally once daily
GS-9450 PlaceboDrug
Placebo to match GS-9450 administered orally once daily
| Study group | Role | What they receive |
|---|---|---|
| Cohort 1 | Experimental | Subjects randomized 3:1 (active:placebo) to receive GS-9450 10 mg/day or placebo. Receives: Drug: GS-9450; Drug: GS-9450 Placebo |
| Cohort 2 | Experimental | Subjects randomized 3:1 (active:placebo) to receive GS-9450 40 mg/day or placebo. Receives: Drug: GS-9450; Drug: GS-9450 Placebo |
| Cohort 3 | Experimental | Subjects randomized 3:1 (active:placebo) to receive GS-9450 80 mg/day or placebo. Receives: Drug: GS-9450; Drug: GS-9450 Placebo |
| Cohort 4 | Experimental | Subjects randomized 3:1 (active:placebo) to receive GS-9450 5 mg/day or placebo. Cohort may or may not be conducted pending blinded review of previous cohorts. Receives: Drug: GS-9450; Drug: GS-9450 Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
Measured: Throughout 7 weeks (2 weeks on treatment and 5 weeks post-treatment)
Secondary outcomes (3)
Plasma pharmacokinetic parameters of GS-9450 and metabolites
Measured: 17 days (through 72 hours after last dose)
Change from baseline in alanine aminotransferase (ALT) levels at Day 14
Measured: Day 14
Change from baseline in noninvasive markers (including cytokeratin 18 fragments) indicative of hepatic apoptosis
Measured: Through Week 5 (2 weeks on treatment and 3 weeks post-treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2008 (estimated)
- Study startApr 2008
- Primary completionOct 2008
- Study completionMar 2009
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
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 33 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- David Oldach, MD, Study chair, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00725803
- Sponsor's protocol ID
- GS-US-227-0102
- Status last verified
- Jun 2014
- First submitted
- 29 Jul 2008
- Last updated
- 19 Jun 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 19 Jun 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2a, Double-Blind, Randomized, Placebo-Controlled, Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Activity of GS-9450, a Caspase Inhibitor, in Subjects With Chronic Hepatitis C (GS-US-227-0102)
- ClinicalTrials.gov ID
- NCT00725803
- Acronym / sponsor ID
- GS-US-227-0102
- Conditions
- HCV Infection
- Keywords
- Hepatitis C, HCV, Fibrosis, Apoptosis, GS-9450
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 33 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Apr 2008
- Primary completion
- Oct 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 31 Jul 2008 (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.
The purpose of this study is to examine the safety, tolerability, pharmacokinetics (studies how the body processes a drug), and initial activity of GS-9450 in preventing liver damage due to scarring, or fibrosis, caused by Hepatitis C Virus (HCV) infection.
Detailed description
Approximately 32 subjects will receive GS 9450 or placebo for 14 consecutive days. Eight subjects will receive treatment within each of four dosing cohorts; 6 randomized to receive GS 9450 and two randomized to placebo:
Cohort 1: GS 9450 10 mg or placebo given daily x 14 days Cohort 2: GS 9450 40 mg or placebo given daily x 14 days Cohort 3: GS 9450 80 mg or placebo given daily x 14 days
If further characterization of the activity profile is deemed necessary, an additional cohort at a lower dose (5 mg) may be enrolled:
Cohort 4: GS 9450 5 mg or placebo given daily x 14 days
Each cohort will be conducted sequentially. Advancement to higher dose cohorts is dependent upon satisfactory safety and tolerability profiles of the preceding cohort as determined by Sponsor review (conducted in consultation with the Lead Investigator[s]). Progression to Cohort 4 (5 mg dose strength) will not require a safety review of Cohort 3 (80 mg dose strength); screening and randomization for Cohort 4 may begin immediately after fully enrolling Cohort 3. Alternatively, if a dose-response relationship is apparent in review of the blinded activity data from the first three cohorts, the final 5 mg cohort may be omitted.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Cohort 1 | Experimental | Drug: GS-9450, Drug: GS-9450 PlaceboSubjects randomized 3:1 (active:placebo) to receive GS-9450 10 mg/day or placebo. |
| Cohort 2 | Experimental | Drug: GS-9450, Drug: GS-9450 PlaceboSubjects randomized 3:1 (active:placebo) to receive GS-9450 40 mg/day or placebo. |
| Cohort 3 | Experimental | Drug: GS-9450, Drug: GS-9450 PlaceboSubjects randomized 3:1 (active:placebo) to receive GS-9450 80 mg/day or placebo. |
| Cohort 4 | Experimental | Drug: GS-9450, Drug: GS-9450 PlaceboSubjects randomized 3:1 (active:placebo) to receive GS-9450 5 mg/day or placebo. Cohort may or may not be conducted pending blinded review of previous cohorts. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- Male or female, aged from 18 to 65 years old, inclusive.
- Willing and able to provide written, informed consent
- Have a body mass index between 19 and 32 kg/m2, inclusive, at screening.
- Have chronic hepatitis C infection of any genotype (and subtype).
- Subjects must be previously treated with pegylated interferon (PEG) or interferon (INF) with or without ribavirin (RBV) and either did not achieve a sustained viral response (undetectable HCV RNA) six months after cessation of anti-viral therapy, or did not tolerate PEG or INF with or without RBV therapy. Subjects who have contraindications to receiving PEG or INF with or without RBV may also be eligible.
Key exclusion criteria (24 listed)
- Pregnant or breast feeding women or women who may wish to become pregnant during the study or within 30 days of study drug administration.
- Males who have partners planning to become pregnant within 30 days of study drug administration.
- Males and females of reproductive potential who are unwilling to use effective method(s) of birth control for a minimum of 30 days after ingestion of study medication
- Coinfection with hepatitis B virus (HBV) or HIV
- Known liver disease of a non-HCV etiology
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-9450GS-9450 capsules administered orally once daily | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
| GS-9450 PlaceboPlacebo to match GS-9450 administered orally once daily | Drug | Cohort 1, Cohort 2, Cohort 3, Cohort 4 |
Primary outcome
Safety and Tolerability
Time frame: Throughout 7 weeks (2 weeks on treatment and 5 weeks post-treatment)
3 secondary outcomes
Plasma pharmacokinetic parameters of GS-9450 and metabolites
Time frame: 17 days (through 72 hours after last dose)
Change from baseline in alanine aminotransferase (ALT) levels at Day 14
Time frame: Day 14
Change from baseline in noninvasive markers (including cytokeratin 18 fragments) indicative of hepatic apoptosis
Time frame: Through Week 5 (2 weeks on treatment and 3 weeks post-treatment)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2014.
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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.
David Oldach, MD study chair
Gilead Sciences
11 sites in 3 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 11 sites in 3 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 13 inclusion and 24 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 19 Jun 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in United States, Germany, Netherlands. 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?
Safety and Tolerability (time frame: Throughout 7 weeks (2 weeks on treatment and 5 weeks post-treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 19 Jun 2014.