| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| thrombocytopenia in subjects with hepatitis C virus (HCV) infection |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 12.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10019744 |
| E.1.2 | Term | Hepatitis C |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the safety and tolerability of open-label eltrombopag when administered once daily |
|
| E.2.2 | Secondary objectives of the trial |
| 1.to evaluate platelet counts before and during antiviral therapy 2.to evaluate maintenence of antiviral therapy 3. to evaluate achievement of antiviral treatment milestones |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
| 1. Male and female subjects, &#8805;18 years of age. 2. Evidence of chronic HCV infection (quantifiable HCV RNA, lower limit of detection of 50 IU/ml). 3. Subjects must be previous participants of TPL103922 (ENABLE 1) or TPL108390 (ENABLE 2) and successfully initiated antiviral treatment in those studies. 4. Subjects must have permanently discontinued all investigational products for ENABLE 1 or 2 within 12 weeks from randomisation in ENABLE 1 or 2 due to reasons of thrombocytopenia. Subjects who continued antiviral therapy beyond 6 weeks must have had some degree of thrombocytopenia during this time, defined as having at least a 50% dose reduction of pegylated IFN (for reasons of thrombocytopenia) for a minimum period of 4 weeks. 5. All subjects must have completed the final 6 month (24 week) SVR and ocular follow-up assessments in ENABLE 1 or ENABLE 2. 6. Subjects who, in the opinion of the investigator, are appropriate candidates for retreatment with peginterferon alfa and ribavirin combination antiviral therapy. 7. A platelet count of <75,000/&#61549;L. 8. All fertile males and females must use two forms of effective contraception between them 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 <1% per year. Double-barrier contraception (condom with spermicidal jelly, or diaphragm with spermicide). Male partner who is sterile prior to the female subjects study entry and is the sole sexual partner for that female. Oral contraceptive (either combined or progesterone only). Any other contraceptive method with a documented failure rate of <1% per year. 10. Subject is able to understand and comply with protocol requirements and instructions and is likely to complete the study as planned. 11. Ability to provide written informed consent. 12. In France, a subject will be eligible for inclusion in this study only if either affiliated to or a beneficiary of a social security category |
|
| E.4 | Principal exclusion criteria |
| 1. Decompensated liver disease. 2. Known hypersensitivity, intolerance or allergy to interferon, ribavirin, eltrombopag or any of their ingredients. 3. Documented history of clinically significant bleeding from oesophageal or gastric varices. 4. Any prior history of arterial or venous thrombosis AND &#61619; 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 5. Pre-existing cardiac disease (congestive heart failure Grade III/IV), (See Appendix 2: New York Heart Association (NYHA) Functional Classification), or arrhythmias known to involve the risk of thromboembolic events (e.g. atrial fibrillation). 6. Evidence of hepatocellular carcinoma by ultrasound, CT or MR scan. 7. Subjects with Human Immunodeficiency Virus (HIV) or active Hepatitis B Virus (HBV) infection (i.e., is positive for Hepatitis B Surface Antigen (HBsAg)). 8. Therapy with any anti-neoplastic or immuno-modulatory treatment &#61603;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. 9. 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 of the skin 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. 10. Pregnant or nursing women. 11. Males with a female partner who is pregnant. 12. History of alcohol/drug abuse or dependence within 6 months of the study start (unless participating in a controlled rehabilitation programme). 13. Treatment with an investigational drug or IFN within 30 days or 5 half-lives (whichever is longer) of the screening visit. 14. History of platelet clumping that prevents reliable measurement of platelet counts. 15. Evidence of portal vein thrombosis on abdominal imaging within 3 months of the baseline visit. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Assessment of safety and tolerability of eltrombopag (AEs, clinical labs, ocular examinations, 12-lead ECGs, Doppler and clinical monitoring/observation) |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | No |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | No |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | No |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
| E.8.2.2 | Placebo | Information not present in EudraCT |
| E.8.2.3 | Other | Information not present in EudraCT |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 10 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 5 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
| |
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 2 |
| E.8.9.1 | In the Member State concerned months | 10 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 3 |
| E.8.9.2 | In all countries concerned by the trial months | 4 |
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