Hepatitis CPhase 1NCT01431898
Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
A Phase 1 study testing GS-9669 tablets in people with Hepatitis C, run by Gilead Sciences at 11 sites in 2 countries.
Trial summary
This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatitis C
- What is being tested?
- GS-9669 tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 82 participants
- Where
- 11 sitesin 2 countries
- Study dates
- Sep 2011to May 2012
- Phase
- Phase 1
- 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 18-65 years of old, inclusive
- Documented chronic HCV infection to be of at least 6 months duration and plasma HCV RNA ≥ 5 log10 IU/mL at screening.
- HCV treatment naïve or PEG-IFN, IFN, and/or RBV experienced (treatment must have ceased at least 3 months prior to screening). Treatment experienced subjects should not exceed 40% of the subjects enrolled in each cohort
- Mono-infection with HCV genotype 1a for Cohorts 1, 2, 3, 4, and 5 and mono-infection with HCV genotype 1b for Cohort 6 and 7.
- Estimated creatinine clearance ≥ 70 mL/min,
- QTcF interval ≤ 450 msec for males and ≤ 470 msec for females, QRS duration < 120 msec, PR interval < 220 msec,
- Body mass index (BMI) of 19.0 to 34.0 kg/m^2, inclusive.
Who cannot join
- Urine drug screen positive for illicit/illegal drugs
- ALT and AST levels > 5 times the upper limit of the normal range (ULN)
- Direct bilirubin > ULN, clinical or other laboratory evidence of hepatic decompensation (i.e., platelets < 90,000/mm^3, prothrombin time ≥ 1.5 × ULN and albumin < 3.5 g/dL) are not eligible for study participation.
- Subjects with an absolute neutrophil count (ANC) < 1,000 cells/mm^3 (< 750 cells/mm^3 for black or African-American subjects), hemoglobin (Hb) < 11 g/dL,
- Coinfected with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or another HCV genotype other than genotype 1a/b are not eligible for study participation.
- Evidence of hepatocellular carcinoma (e.g., a-fetoprotein > 50 ng/mL or as indicated by recent ultrasound or other standard of care measure)
Show all 9Show fewer
- History of significant cardiac disease. The following ECG abnormalities at screening are exclusionary: QTcF (QT corrected using Fridericia's formula=QT/RR^0.333) > 450 msec for males and > 470 for females; QRS > 120 msec (left or right hemiblock is not exclusionary); PR interval > 220 msec; bradycardia (< 45 beats per minute); second or third degree heart block.
- History of clinically-significant illness or any other major medical disorder that may interfere with subject treatment, assessment or compliance with the protocol
- 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
Trial locations and contacts
11 sites in 2 countries.
11 sites in 2 countries
United States10 sites
Avail Clinical Research, LLC
DeLand, Florida, 32720
Impact Clinical Trials
Las Vegas, Nevada, 89106
Impact Clinical Trials
Los Angeles, California, 90036
Orlando Clinical Research Center
Orlando, Florida, 32809
CRI Worldwide
Philadelphia, Pennsylvania, 19139
Lifetree Clinical Research, LC
Salt Lake City, Utah, 84106
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
Alamo Medical Research
San Antonio, Texas, 78215
Charles River Clinical Services Northwest
Tacoma, Washington, 98418
CRI Worldwide
Willingboro, New Jersey, 08046
About this study
Official title: A Phase 1b, Randomized, Single-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.
- Conditions
- Hepatitis C
- Being tested
- GS-9669 tablets, Placebo to Match GS-9669 tablet
- Keywords
- HCV RNA, Polymerase inhibitor, Treatment naïve and Treatment experienced, GS-9669, Hepatitis C, HCV
- Medical subject headings
- Hepatitis C
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-9669 tabletsDrug
Also called Cohort 1 (N = 10, genotype 1a): 100 mg GS-9669 or placebo BID with, food [total daily dose (TDD) = 200 mg] for 3 days;, Cohort 2 (N = 10, genotype 1a): 400 mg GS-9669 or placebo BID with, food (TDD = 800 mg) for 3 days;
Placebo to Match GS-9669 tabletDrug
| Study group | Role | What they receive |
|---|---|---|
| Multiple-dose, dose-escalation study of GS-9669 | Experimental | Multiple-dose, dose-escalation study of GS-9669, a nonnucleotide NS5B inhibitor of hepatitis C virus (HCV), in subjects with chronic HCV infection. Dosing is planned in up to 7 unique dosing cohorts. Each cohort will be comprised of 10 genotype 1a (Cohorts 1, 2, 3, 4, and 5) or genotype 1b (Cohort 6 and 7), with eight subjects randomized to receive active drug and two subjects randomized to receive placebo per cohort. Receives: Drug: GS-9669 tablets; Drug: Placebo to Match GS-9669 tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety and Tolerability
To evaluate safety and tolerability of escalating multiple oral doses of GS 9669.
Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs, and 12-lead ECGs at various time points during the study.
Measured: through 24 weeks of off-treatment follow-up
Antiviral Activity
To evaluate antiviral activity of GS-9669 against HCV in genotype-1a and 1b (GT1a/b) subjects. This will be evaluated using change from baseline in plasma HCV RNA. Reduction in HCV RNA will be summarized as categorical (as < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL) reduction from baseline.
Measured: through 24 weeks of off-treatment follow-up
Secondary outcomes (3)
Viral Dynamics and Pharmacodynamics
To characterize the viral dynamics of GS-9669. The median change from baseline in HCV RNA and time-weighted average change from baseline through Day 3 will be assessed based on plasma HCV RNA sampling times to characterize the viral dynamics of GS-9669.
Measured: Through 17 days of therapy
composite of Pharmacokinetics
To characterize the plasma PK parameters of GS-9669. The secondary PK endpoints will be evaluated using standard non-compartmental methods. Relevant PK parameters will be determined using standard non-compartmental methods with the linear-logarithmic trapezoidal rule utilizing a PK data analysis program (e.g., WinNonlin®) for GS-9669 as appropriate: Cmax, Tmax, Clast, Tlast, Ctau, λz, AUC0-last, AUCtau, , CL/F, and T½.
Measured: Through 17 days of therapy
Genotypic Changes
To characterize genotypic changes from baseline in the NS5B coding region of HCV following multiple dose administration of GS-9669 and for up to 24 weeks thereafter
Measured: through 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.
- First posted12 Sep 2011 (estimated)
- Study startSep 2011
- Primary completionDec 2011
- Study completionMay 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Hepatitis CStudies 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 1
- Primary purpose
- Treatment
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 82 participants (actual)
Sponsor and investigators
- Lead sponsor
- Gilead Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Stephen Rossi, PharmD, Study director, Gilead Sciences
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01431898
- Sponsor's protocol ID
- GS-US-257-0102
- Status last verified
- Mar 2012
- First submitted
- 1 Sep 2011
- Last updated
- 25 Jul 2012
- Results posted
- No
Publications
Dvory-Sobol H, Voitenleitner C, Mabery E, Skurnac T, Lawitz EJ, McHutchison J, Svarovskaia ES, Delaney W, Miller MD, Mo H. Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2014 Nov;58(11):6599-606. doi: 10.1128/AAC.02815-14. Epub 2014 Aug 25.
PubMed 25155588Fenaux M, Eng S, Leavitt SA, Lee YJ, Mabery EM, Tian Y, Byun D, Canales E, Clarke MO, Doerffler E, Lazerwith SE, Lew W, Liu Q, Mertzman M, Morganelli P, Xu L, Ye H, Zhang J, Matles M, Murray BP, Mwangi J, Zhang J, Hashash A, Krawczyk SH, Bidgood AM, Appleby TC, Watkins WJ. Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2013 Feb;57(2):804-10. doi: 10.1128/AAC.02052-12. Epub 2012 Nov 26.
PubMed 23183437
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1b, Randomized, Single-Blind, Multiple-Dose Ranging Study Evaluating the Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
- ClinicalTrials.gov ID
- NCT01431898
- Acronym / sponsor ID
- GS-US-257-0102
- Conditions
- Hepatitis C
- Keywords
- HCV RNA, Polymerase inhibitor, Treatment naïve and Treatment experienced, GS-9669, Hepatitis C, HCV
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 82 participants (actual)
- Lead sponsor
- Gilead SciencesIndustry (pharma, biotech, devices)
- Study start
- Sep 2011
- Primary completion
- Dec 2011 (actual)
- Study completion
- May 2012 (actual)
- First posted
- 12 Sep 2011 (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.
This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.
Study design
- Primary purpose
- Treatment
- Masking
- Single blind (participant)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Multiple-dose, dose-escalation study of GS-9669 | Experimental | Drug: GS-9669 tablets, Drug: Placebo to Match GS-9669 tabletMultiple-dose, dose-escalation study of GS-9669, a nonnucleotide NS5B inhibitor of hepatitis C virus (HCV), in subjects with chronic HCV infection. Dosing is planned in up to 7 unique dosing cohorts. Each cohort will be comprised of 10 genotype 1a (Cohorts 1, 2, 3, 4, and 5) or genotype 1b (Cohort 6 and 7), with eight subjects randomized to receive active drug and two subjects randomized to receive placebo per cohort. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Adult subjects 18-65 years of old, inclusive
- Documented chronic HCV infection to be of at least 6 months duration and plasma HCV RNA ≥ 5 log10 IU/mL at screening.
- HCV treatment naïve or PEG-IFN, IFN, and/or RBV experienced (treatment must have ceased at least 3 months prior to screening). Treatment experienced subjects should not exceed 40% of the subjects enrolled in each cohort
- Mono-infection with HCV genotype 1a for Cohorts 1, 2, 3, 4, and 5 and mono-infection with HCV genotype 1b for Cohort 6 and 7.
- Estimated creatinine clearance ≥ 70 mL/min,
Key exclusion criteria (9 listed)
- Urine drug screen positive for illicit/illegal drugs
- ALT and AST levels > 5 times the upper limit of the normal range (ULN)
- Direct bilirubin > ULN, clinical or other laboratory evidence of hepatic decompensation (i.e., platelets < 90,000/mm^3, prothrombin time ≥ 1.5 × ULN and albumin < 3.5 g/dL) are not eligible for study participation.
- Subjects with an absolute neutrophil count (ANC) < 1,000 cells/mm^3 (< 750 cells/mm^3 for black or African-American subjects), hemoglobin (Hb) < 11 g/dL,
- Coinfected with hepatitis B virus (HBV), human immunodeficiency virus (HIV), or another HCV genotype other than genotype 1a/b are not eligible for study participation.
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-9669 tabletsAlso: Cohort 1 (N = 10, genotype 1a): 100 mg GS-9669 or placebo BID with, food [total daily dose (TDD) = 200 mg] for 3 days;, Cohort 2 (N = 10, genotype 1a): 400 mg GS-9669 or placebo BID with, food (TDD = 800 mg) for 3 days; | Drug | Multiple-dose, dose-escalation study of GS-9669 |
| Placebo to Match GS-9669 tablet | Drug | Multiple-dose, dose-escalation study of GS-9669 |
Primary outcome
Safety and Tolerability
Time frame: through 24 weeks of off-treatment follow-up
To evaluate safety and tolerability of escalating multiple oral doses of GS 9669. Safety will be assessed during the study through the reporting of adverse events, clinical laboratory tests, physical examinations, vital signs, and 12-lead ECGs at various time points during the study.
Antiviral Activity
Time frame: through 24 weeks of off-treatment follow-up
To evaluate antiviral activity of GS-9669 against HCV in genotype-1a and 1b (GT1a/b) subjects. This will be evaluated using change from baseline in plasma HCV RNA. Reduction in HCV RNA will be summarized as categorical (as < 1, ≥ 1 to <2, ≥ 2 to <3, or ≥ 3 log10 IU/mL) reduction from baseline.
3 secondary outcomes
Viral Dynamics and Pharmacodynamics
Time frame: Through 17 days of therapy
composite of Pharmacokinetics
Time frame: Through 17 days of therapy
Genotypic Changes
Time frame: through 24 weeks of off-treatment follow-up
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 25 Jul 2012.
- Derived from this study: PubMed 25155588Dvory-Sobol H, Voitenleitner C, Mabery E, Skurnac T, Lawitz EJ, McHutchison J, Svarovskaia ES, Delaney W, Miller MD, Mo H. Clinical and in vitro resistance to GS-9669, a thumb site II nonnucleoside inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2014 Nov;58(11):6599-606. doi: 10.1128/AAC.02815-14. Epub 2014 Aug 25.
- Derived from this study: PubMed 23183437Fenaux M, Eng S, Leavitt SA, Lee YJ, Mabery EM, Tian Y, Byun D, Canales E, Clarke MO, Doerffler E, Lazerwith SE, Lew W, Liu Q, Mertzman M, Morganelli P, Xu L, Ye H, Zhang J, Matles M, Murray BP, Mwangi J, Zhang J, Hashash A, Krawczyk SH, Bidgood AM, Appleby TC, Watkins WJ. Preclinical characterization of GS-9669, a thumb site II inhibitor of the hepatitis C virus NS5B polymerase. Antimicrob Agents Chemother. 2013 Feb;57(2):804-10. doi: 10.1128/AAC.02052-12. Epub 2012 Nov 26.
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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.
Stephen Rossi, PharmD study director
Gilead Sciences
11 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GS-9669 tablets in people with Hepatitis C, run by Gilead Sciences at 11 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 7 inclusion and 9 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 25 Jul 2012. 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, 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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: through 24 weeks of off-treatment follow-up). The study lists 2 primary outcomes in all. 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 NCT01431898, which also lists 2 linked publications.
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 25 Jul 2012.