A Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Antiviral Effect of GSK2336805 With Pegylated Interferon and Ribavirin in Patients with Chronic Hepatitis C Infection.
- Conditions
- Hepatitis C virusMedDRA version: 16.0Level: LLTClassification code 10019752Term: Hepatitis C virus (HCV)System Organ Class: 100000004848Therapeutic area: Diseases [C] - Virus Diseases [C02]
- Registration Number
- EUCTR2012-000523-40-BG
- Lead Sponsor
- GlaxoSmithKline Research and Devlopment Ltd
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 115
1. Is capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
2. Is male or female aged 18 to 70 years, inclusive, at Screening.
3. Has chronic genotype 1 or genotype 4 (as assessed by VERSANT HCV Genotype assay 2.0 (LiPA); Siemens Healthcare Diagnostics, Deerfield, Illinois) HCV infection documented by at least 1 measurement of serum HCV RNA =100,000 IU/mL measured during Screening by the COBAS High Pure/COBAS
TaqMan HCV Test v2.0 (Roche Molecular Diagnostics, Pleasanton, California) and at least one of the following:
• A positive anti-HCV antibody, HCV RNA, or HCV genotype test at least 6 months prior to Baseline (Day 1) together with positive HCV RNA and anti-HCV antibody tests at the time of Screening; or
• A positive HCV RNA test and anti-HCV antibody test at the time of Screening together with either a liver biopsy consistent with chronic HCV infection (or a liver biopsy performed before enrollment with evidence of CHC disease, such as the presence of fibrosis).
4. Is naïve to all HCV antiviral treatment(s), including, but not limited to, immunomodulatory and nucleoside/nucleotide treatments for chronic HCV infection.
5. Agrees to IL28B genotyping.
6. Is a subject, who, in the opinion of the investigator, is an appropriate candidate for PEG/RIBA/protease inhibitor combination therapy for genotype 1 subjects and PEG/RIBA combination therapy for genotype 4 subjects.
7. Has a body mass index >18 kg/m2 but not exceeding 36 kg/m2.
8. Has a liver biopsy obtained within 3 years (36 calendar months) prior to the Day 1 visit, with a fibrosis classification of noncirrhotic as judged by a local pathologist (defined as Knodell =3, Metavir =2, Ishak =4, or Batts and Ludwig =2). Both incomplete and transition to cirrhosis (e.g., Metavir score 3) are considered as
cirrhosis. If no recent (<36 months) liver biopsy is available, a study-qualifying biopsy must be performed prior to Baseline (Day 1).
9. For all fertile males and females, must use 2 forms of effective contraception (as defined in inclusion criterion #10) between them during treatment and during the 24 weeks after treatment ends.
10. For females, is eligible to enter and participate in the study if she is of
• Nonchildbearing potential (i.e., physiologically incapable of becoming pregnant) including any female who
• Has had a hysterectomy
• Has had a bilateral oophorectomy (ovariectomy)
• Has had a bilateral tubal ligation
• Is postmenopausal (demonstrate total cessation of menses for greater than 1 year)
• Childbearing potential and has a negative urine or serum pregnancy test at Screening and within the 24-hour period prior to the first dose of study medication and completely abstains from intercourse for 2 weeks before exposure to the study medication, throughout the clinical study, and for
24 weeks after completion or premature discontinuation from this study or uses 2 of the following acceptable methods of contraception throughout the clinical study and for 24 weeks after completion or premature discontinuation from this study:*
• Any intrauterine device with a documented failure rate of <1% per year
• Double-barrier contraception (condom, diaphragm, or cervical cap used with spermicidal jelly)
• Male partner who is sterile prior to the female subject’s study entry and is the sole sexual partner for that female
• Any other contraceptive method with a documented failure rate of <1% per year
11. Is o
1. Has positive test at Screening for hepatitis B surface antigen (HBsAg) or antihuman immunodeficiency virus antibody.
2. Has a history of any other clinically significant chronic liver disease (e.g., hemochromatosis, autoimmune hepatitis, Wilson's disease, 1-antitrypsin deficiency, alcoholic liver disease, >Grade 1 nonalcoholic steatohepatitis, and toxin exposures) (Note: Subjects with Gilbert’s syndrome who otherwise meet all inclusion/exclusion criteria are eligible.)
3. Has a history of ascites, variceal hemorrhage, hepatic encephalopathy, or conditions consistent with decompensated liver disease.
4. Has positive results on urine screen for drugs of abuse test at Screening (unless used as medical treatment, e.g., with a prescription).
5. Has a history of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation program).
6. Has screening ECG corrected QT (QTc) interval value >450 ms and/or clinically significant ECG findings.
7. Has personal or family history of torsade de pointes findings.
8. Is pregnant or nursing.
9. Is male with a female partner who is pregnant.
10. Has abnormal hematological and biochemical parameters, including:
• Neutrophil count <1500 cells/mm3 (or <1250 cells/mm3 for African
American/Black subjects)
• Hemoglobin <11 g/dL in females or <12 g/dL in males
• Creatinine =1.5 × the upper limit of normal (ULN)
• Estimated creatinine clearance =50 mL/min (as calculated using the Cockcroft-Gault formula)
• ALT, AST, or alkaline phosphatase =5 × ULN
• Total bilirubin =2.0 × ULN (except subjects with Gilbert's syndrome)
• Albumin =3.0 g/dL
• Platelet count =90,000/mm3
11. Has history of major organ transplantation with an existing functional graft.
12. Has thyroid dysfunction not adequately controlled.
13. Has a history of any one of the following:
• Suicide attempt or hospitalization for depression in the past 5 years
• Any current (within 6 months) severe or poorly controlled psychiatric disorder
• The following subjects are eligible for study participation but must be assessed
and followed (if recommended) by a mental health professional:
• Subjects who have had a severe or poorly controlled psychiatric disorder more than 6 months ago but less than 5 years ago
14. Has a history or current evidence of immunologic disorder; cardiac or pulmonary disease; seizure disorder; or cancer or history of malignancy that in the opinion of the investigator makes the subject unsuitable for the study.
15. Has been treated with herbal or natural remedies with antiviral activity within 30 days of the baseline visit or has a history of having received any systemic antineoplastic or immunomodulatory treatment (including mycophenolate mofetil, thymosin alpha, supraphysiologic doses of steroids >10 mg/day and radiation) within 6 months of the baseline visit or expects that such treatment will be needed at any time during the study.
16. Has participated in a clinical study with an investigational drug, biologic, or device within 3 months prior to the first dose administration.
17. Has a history of a known allergy to antiviral medications, including telaprevir, PEG, or RIBA, or any excipient in the investigational product or history of drug or other allergy that, in the opinion of the investigator, contradicts participation.
18. Requires prohibited medications.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method