Clinical trial NCT01431898: Safety, Tolerability, Pharmacokinetics and Antiviral Activity of GS-9669 in Subjects With Chronic Hepatitis C Virus Infection
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Hepatitis C
Keywords: HCV RNA
Polymerase inhibitor
Treatment naïve and Treatment experienced
GS-9669
Hepatitis C
HCV
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2011-09-12
Enrollment: 82
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: This is a research study to evaluate the safety, tolerability and anti-viral activity of GS-9669 in patients with Hepatitis C infection.


Eligibility criteria: 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

Primary outcomes:
measure: Safety and Tolerability
timeFrame: through 24 weeks of off-treatment follow-up
measure: Antiviral Activity
timeFrame: through 24 weeks of off-treatment follow-up
Secondary outcomes:
measure: Viral Dynamics and Pharmacodynamics
timeFrame: Through 17 days of therapy
measure: composite of Pharmacokinetics
timeFrame: Through 17 days of therapy
measure: Genotypic Changes
timeFrame: through 24 weeks of off-treatment follow-up
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Impact Clinical Trials
state: California
city: Deland
country: United States
facility: Avail Clinical Research, LLC
state: Florida
city: Orlando
country: United States
facility: Orlando Clinical Research Center
state: Florida
city: Las Vegas
country: United States
facility: Impact Clinical Trials
state: Nevada
city: Willingboro
country: United States
facility: CRI Worldwide
state: New Jersey
city: Philadelphia
country: United States
facility: CRI Worldwide
state: Pennsylvania
city: San Antonio
country: United States
facility: Alamo Medical Research
state: Texas
city: Salt Lake City
country: United States
facility: Lifetree Clinical Research, LC
state: Utah
city: Salt Lake City
country: United States
facility: University of Utah Health Sciences Center
state: Utah
city: Tacoma
country: United States
facility: Charles River Clinical Services Northwest
state: Washington
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
affiliation: Gilead Sciences
name: Stephen Rossi, PharmD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.