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

This study has been terminated.
(Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.)
Sponsor:
Information provided by (Responsible Party):
Gilead Sciences
ClinicalTrials.gov Identifier:
NCT00874796
First received: April 2, 2009
Last updated: January 3, 2014
Last verified: January 2014
  Purpose

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.


Condition Intervention Phase
HCV Infection
Drug: GS-9450
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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)

Resource links provided by NLM:


Further study details as provided by Gilead Sciences:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Change (absolute, percent) from baseline in the Knodell necroinflammatory score [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: Yes ]
  • Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
  • Change from baseline in the percent of apoptotic cells [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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

  • Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes [ Time Frame: Baseline to Week 24 ] [ Designated as safety issue: No ]
    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

  • Change From Baseline in HCV RNA [ Time Frame: Baseline to to Week 24 ] [ Designated as safety issue: No ]

Enrollment: 307
Study Start Date: May 2009
Study Completion Date: July 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GS-9450 10 mg/day
GS-9450 taken as one 10 mg capsule by mouth once daily
Drug: GS-9450
Taken as one capsule by mouth once daily
Experimental: GS-9450 40 mg/day
GS-9450 taken as one 40 mg capsule by mouth once daily
Drug: GS-9450
Taken as one capsule by mouth once daily
Placebo Comparator: Placebo
Placebo taken as one placebo capsule by mouth once daily
Drug: Placebo
Taken as one placebo capsule (matching in appearance to GS-9450 capsules) by mouth once daily

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

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

Exclusion Criteria:

  • 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
  • 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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00874796

  Show 73 Study Locations
Sponsors and Collaborators
Gilead Sciences
Investigators
Study Director: Ken Hirsch, MD Gilead Sciences
  More Information

No publications provided

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00874796     History of Changes
Other Study ID Numbers: GS-US-227-0106
Study First Received: April 2, 2009
Last Updated: January 3, 2014
Health Authority: United States: Food and Drug Administration
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Gilead Sciences:
apoptosis
liver inflammation
hepatitis C

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Chronic
Hepatitis C
Virus Diseases
Hepatitis C, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Flaviviridae Infections

ClinicalTrials.gov processed this record on April 15, 2014