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

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ClinicalTrials.gov Identifier: NCT00874796
Recruitment Status : Terminated (Reports of significant laboratory abnormalities and adverse events in a number of clinical study participants.)
First Posted : April 3, 2009
Last Update Posted : February 4, 2014
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

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 or disease Intervention/treatment Phase
HCV Infection Drug: GS-9450 Drug: Placebo Phase 2

Study Design

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 307 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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)
Study Start Date : May 2009
Primary Completion Date : April 2010
Study Completion Date : July 2010

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arms and Interventions

Arm Intervention/treatment
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


Outcome Measures

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Change (absolute, percent) from baseline in the Knodell necroinflammatory score [ Time Frame: Baseline to Week 24 ]
  2. Change (absolute, percent) from pretreatment in alanine aminotransferase (ALT) levels [ Time Frame: Baseline to Week 24 ]
  3. 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 ]
  4. Change (absolute, percent) from baseline in cytokeratin-18 caspase cleavage fragment levels [ Time Frame: Baseline to Week 24 ]
  5. Change from baseline in hepatic collagen staining area as measured by morphometry of liver biopsy specimens [ Time Frame: Baseline to Week 24 ]
  6. Change from baseline in the percent of apoptotic cells [ Time Frame: Baseline to Week 24 ]
    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

  7. Change from baseline in percent of anti-M30 monoclonal antibody-positive hepatocytes [ Time Frame: Baseline to Week 24 ]
    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

  8. Change From Baseline in HCV RNA [ Time Frame: Baseline to to Week 24 ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00874796


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

Responsible Party: Gilead Sciences
ClinicalTrials.gov Identifier: NCT00874796     History of Changes
Other Study ID Numbers: GS-US-227-0106
First Posted: April 3, 2009    Key Record Dates
Last Update Posted: February 4, 2014
Last Verified: January 2014

Keywords provided by Gilead Sciences:
apoptosis
liver inflammation
hepatitis C

Additional relevant MeSH terms:
Infection
Communicable Diseases
Hepatitis
Hepatitis C
Hepatitis, Chronic
Hepatitis C, Chronic
Virus Diseases
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Flaviviridae Infections
RNA Virus Infections