Thrombocytopenic subjects with hepatitis C viral infection MedDRA version: 9.1 Level: LLT Classification code 10019744 Term: Hepatitis C
Conditions
Interventions
Product Name: Eltrombopag
Product Code: SB-497115
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Eltrombopag
CAS Number: C
Sponsors
GlaxoSmithKline Research & Development Ltd
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male and female subjects, =18 years of age. 2. Evidence of chronic HCV infection (quantifiable HCV RNA). 3. Subjects who, in the opinion of the investigator, are appropriate candidates for peginterferon alfa-2b and ribavirin combination antiviral therapy. 4. A baseline platelet count 11.0g/dL for men or at least 10.0g/dL for women 6. Absolute neutrophil count (ANC) at least 750/mm3 and no history of infections associated with neutropenia 7. Creatinine clearance at least 50mL/minute. 8. All fertile males must use two forms of effective contraception during treatment and during the 24 weeks after treatment end. 9. A female is eligible to enter and participate in the study if she is of: • Non-childbearing 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 post-menopausal (demonstrate total cessation of menses for greater than one year) • Childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of eltrombopag, and completely abstains from intercourse for two weeks before exposure to the study drug, throughout the clinical trial, and for 24 weeks after completion or premature discontinuation from the study. • Childbearing potential, has a negative urine or serum pregnancy test at screening and within the 24-hour period prior to the first dose of eltrombopag, and uses two of the following acceptable methods of contraception: • Any intrauterine device (IUD) with a documented failure rate of =65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Non-responders to previous treatment with peginterferon and ribavirin who failed to achieve a SVR for reasons other than thrombocytopenia, despite an optimal course (dose and duration) of combination therapy with peginterferon and ribavirin. 2. Decompensated liver disease, e.g. Child-Turcotte-Pugh score >6 (See Appendix 3) or history of ascites or hepatic encephalopathy or current evidence of ascites. 3. Known hypersensitivity, intolerance or allergy to IFN, ribavirin, eltrombopag or any of their ingredients. 4. Serious cardiac, cerebrovascular, or pulmonary disease that, in the opinion of the investigator, would preclude treatment with Peginterferon alfa-2a and ribavirin. 5. Subjects with a history of any one of the following: • Suicide attempt or hospitalisation 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: a. Subjects who have had a severe or poorly controlled psychiatric disorder more than 6 months ago but less than 5 years ago. 6. Seizure disorder that has not been well controlled. 7. Documented history of clinically significant bleeding from oesophageal or gastric varices. 8. Subjects with haemoglobinopathies, e.g. sickle cell anaemia, thalassemia major. 9. Any prior history of arterial or venous thrombosis AND ? two of the following risk factors: hereditary thrombophilic disorders (e.g. Factor V Leiden, ATIII deficiency, etc), hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer. 10. Pre-existing cardiac disease (congestive heart failure New York Heart Association (NYHA) Grade III/IV), (See Appendix 4), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation), or subjects with a QTc >450 msec. 11. Evidence of hepatocellular carcinoma by ultrasound, CT or MR scan. 12. Laboratory evidence of infection with Human Immunodeficiency Virus (HIV) or active Hepatitis B Virus (HBV) infection (i.e., is positive for Hepatitis B Surface Antigen (HBsAg)). 13. Any disease condition associated with active bleeding or requiring anticoagulation with heparin or warfarin. 14. Therapy with any anti-neoplastic or immuno-modulatory treatment ?6 months prior to the first dose of eltrombopag. Exception: Physiologic doses of steroids or short courses of steroids (e.g., steroid taper for exacerbation of asthma) are not excluded. 15. Subjects who have had a malignancy diagnosed and/or treated within the past 5 years, except for subjects with localised basal or squamous cell carcinoma treated by local excision or subjects with malignancies who have been adequately treated and, in the opinion of the oncologist, have an excellent chance of cancer-free survival. 16. Pregnant or nursing women. 17. Males with a female partner who is pregnant. 18. History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a contro
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of eltrombopag treatment on Sustained Virological Response (SVR) in thrombocytopenic subjects (platelets <75,000/microL) with hepatitis C virus (HCV) infection; Secondary Objective: 1. To evaluate ability of eltrombopag to enable initiation of antiviral therapy in thrombocytopenic subjects with HCV infection 2. To evaluate ability of eltrombopag to maintain antiviral therapy in thrombocytopenic subjects with HCV infection 3. To evaluate safety/tolerability of eltrombopag when administered once daily in thrombocytopenic subjects with HCV infection 4. To evaluate effect of eltrombopag on platelet counts in thrombocytopenic subjects with HCV infection 5. To describe PK of eltrombopag and explore its relationship with relevant safety & efficacy endpoints 6. To evaluate effects of eltrombopag treatment on antiviral treatment outcome measures (RVR, EVR and ETR in thrombocytopenic subjects with HCV infection 7. To evaluate impact of eltrombopag on subject reported symptoms and HRQoL ;Primary end point(s): Sustained virological response (SVR) rate defined as percentage of subjects with non-detectable HCV-RNA at 24 weeks post-completion of the planned treatment period (i.e., Week 48 for genotype 2/3 or Week 72 for non-genotype 2/3). | — |
Countries
Belgium, Czech Republic, France, Germany, Greece, Italy, Netherlands, Slovakia, Spain
Outcome results
None listed