- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01431898
Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
July 23, 2012 updated by: Gilead Sciences
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
82
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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San Juan, Puerto Rico, 00927
- Fundacion de Investigacion de Diego
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California
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Los Angeles, California, United States, 90036
- Impact Clinical Trials
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Florida
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Deland, Florida, United States, 32720
- Avail Clinical Research, LLC
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Orlando, Florida, United States, 32809
- Orlando Clinical Research Center
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Nevada
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Las Vegas, Nevada, United States, 89106
- Impact Clinical Trials
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New Jersey
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Willingboro, New Jersey, United States, 08046
- CRI Worldwide
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19139
- CRI Worldwide
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Texas
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San Antonio, Texas, United States, 78215
- Alamo Medical Research
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Utah
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Salt Lake City, Utah, United States, 84132
- University of Utah Health Sciences Center
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Salt Lake City, Utah, United States, 84106
- Lifetree Clinical Research, LC
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Washington
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Tacoma, Washington, United States, 98418
- Charles River Clinical Services Northwest
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 65 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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)
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Masking: Single
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Multiple-dose, dose-escalation study of GS-9669
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.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Safety and Tolerability
Time Frame: through 24 weeks of off-treatment follow-up
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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. |
through 24 weeks of off-treatment follow-up
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Antiviral Activity
Time Frame: through 24 weeks of off-treatment follow-up
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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.
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through 24 weeks of off-treatment follow-up
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Viral Dynamics and Pharmacodynamics
Time Frame: Through 17 days of therapy
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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.
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Through 17 days of therapy
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composite of Pharmacokinetics
Time Frame: Through 17 days of therapy
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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.
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Through 17 days of therapy
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Genotypic Changes
Time Frame: through 24 weeks of off-treatment follow-up
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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
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through 24 weeks of off-treatment follow-up
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Study Director: Stephen Rossi, PharmD, Gilead Sciences
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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.
- Fenaux 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2011
Primary Completion (Actual)
December 1, 2011
Study Completion (Actual)
May 1, 2012
Study Registration Dates
First Submitted
September 1, 2011
First Submitted That Met QC Criteria
September 9, 2011
First Posted (Estimate)
September 12, 2011
Study Record Updates
Last Update Posted (Estimate)
July 25, 2012
Last Update Submitted That Met QC Criteria
July 23, 2012
Last Verified
March 1, 2012
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis, Chronic
- Hepatitis
- Hepatitis A
- Hepatitis C
- Virus Diseases
- Hepatitis C, Chronic
Other Study ID Numbers
- GS-US-257-0102
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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