| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Thrombocytopenic subjects with hepatitis C viral infection |
|
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 9.1 |
| 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 effect of eltrombopag treatment on SVR in thrombocytopenic subjects (platelets <75,000/microL) with hepatitis C virus (HCV) infection |
|
| E.2.2 | Secondary objectives of the trial |
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 |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal 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-2a and ribavirin combination antiviral therapy.
4. A baseline platelet count <75,000/microL
5. Haemoglobin concentration >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 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 subject’s 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. |
|
| E.4 | Principal 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 controlled rehabilitation programme).
19. Treatment with an investigational drug or IFN within 30 days or 5 half-lives (whichever is longer) of the screening visit.
20. History of platelet clumping that prevents reliable measurement of platelet counts.
21. History of major organ transplantation with an existing functional graft.
22. Thyroid dysfunction not adequately controlled.
23. Subjects planning to have cataract surgery
24. 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) |
| 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). |
|
| 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 | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | Yes |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Yes |
| 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 | Information not present in EudraCT |
| E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
| E.7.1.3 | Other | Information not present in EudraCT |
| 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 | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | Yes |
| 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 | Yes |
| E.8.1.7.1 | Other trial design description |
| Part A is open, Part B randomised |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| 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 | 36 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 86 |
| 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 | 3 |
| E.8.9.1 | In the Member State concerned months | 6 |
| 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 | 6 |
Print
