| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Immune thrombocytopenic purpura (ITP) |
|
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | Yes |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To describe the long-term safety and tolerability of oral eltrombopag treatment of subjects with ITP with or without concomitant ITP medication. |
|
| E.2.2 | Secondary objectives of the trial |
• To describe the clinical efficacy, pharmacodynamics, and durability of efficacy response to eltrombopag when administered to previously treated subjects with ITP as measured by platelet counts.
• To describe the effect of re-treatment on platelet counts in subjects previously treated with eltrombopag.
• To gain information on the optimal dosing of eltrombopag in individual subjects with ITP.
• To describe the effect of eltrombopag on reduction and/or sparing of concomitant ITP therapies, while maintaining a platelet count ≥ 50,000/L.
• To assess the impact of eltrombopag on physical and mental health status, the symptoms of fatigue and bleeding and bruising, and the impact of such symptoms on health-related quality of life.
Exploratory objectives are to assess the effect of administration of eltrombopag on anti-platelet antibody titers and to use proteomic analysis to identify proteins that correlate with safety and tolerability and/or predict response to eltrombopag. |
|
| E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
| E.3 | Principal inclusion criteria |
1. Subject has signed and dated a written informed consent.
2. Adults (at least 18 years) diagnosed with ITP according to the American Society for Hematology/British Committee for Standards in Haematology (ASH/BCSH) guidelines. In addition, the peripheral blood smear should support the diagnosis of ITP with no evidence of other disease causative of thrombocytopenia (e.g., pseudo thrombocytopenia, myelofibrosis). The physical examination should be normal or at least not show signs suggestive of any disease likely to be associated with thrombocytopenia.
3. Prior randomization and completion of treatment and follow up periods in an ITP study of eltrombopag (e.g., TRA100773 or TRA102537/RAISE).
4. Subjects previously enrolled in Study TRA100773 must have completed the prescribed follow-up ophthalmic assessment at 6 months without observation of an ocular event of clinical concern.
5. Subjects previously enrolled in TRA102537/RAISE must have completed the treatment and follow-up periods as defined in that protocol.
6. Subject experienced no eltrombopag-related SAE or other drug intolerance on prior eltrombopag study even if resolved; subjects discontinued from previous study due to toxicity will not be eligible unless they received placebo.
7. Subject has no intercurrent medical event, including evidence of new cataract formation or any thrombosis.
8. Ophthalmic examinations performed during prior studies have not identified ocular events of clinical concern that changed from the screening visit (baseline eye assessment).
9. Subjects must have either initially responded (platelet count > 100,000/µL) to a previous ITP therapy or have had a bone marrow biopsy consistent with ITP within 3 years to rule out myelodysplasia or other causes of thrombocytopenia.
10. Previous therapy for ITP with immunoglobulins (IVIg and anti-D), and cyclophosphamide must have been completed at least 4 weeks prior to Day 1. Treatment with rituximab must have been completed at least 12 weeks prior to Day 1 of study treatment. Subjects who have had a splenectomy must have had the procedure performed at least 4 weeks prior to study Day 1.
11. Subjects treated with corticosteroids must be receiving a dose that has been stable (dose change of +/- 5% is acceptable) for at least 1 month prior to Day 1 of study. Subjects treated with cyclosporin A, mycophenolate mofetil, azathioprine or danazol must be receiving a dose that has been stable (dose change of +/- 5% is acceptable) for at least 3 months prior to Day 1 of study treatment.
12. Normal prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT), no history of hypercoagulable state.
13. A complete blood count (CBC), within the reference range (including differential not indicative of a disorder other than ITP), with the following exceptions:
• Hemoglobin: Subjects with hemoglobin levels between 10.0 g/dL and the lower limit of normal are eligible for inclusion, if anemia is clearly attributable to ITP (i.e., excessive blood loss).
• ANC greater than 1500/microL (1.5 x 109/L) is required for inclusion (elevated WBC/ANC due to steroid treatment is acceptable).
14. The following clinical chemistries must be within the normal reference range: creatinine, ALT, AST, total bilirubin, total albumin and alkaline phosphatase.
15. Subject is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must either be of non-childbearing potential (hysterectomy, bilateral oopherectomy, bilateral tubal ligation or post-menopausal > 1 year), or of childbearing potential and use one of the following acceptable methods of contraception from two weeks prior to administration of study medication, throughout the study, and 28 days after completion or premature discontinuation from the study:
• Complete abstinence from intercourse;
• Intrauterine device (IUD);
• Two forms of barrier contraception (diaphragm plus spermicide, and for males condom plus spermicide);
• Male partner is sterile prior to entry into the study and is the only partner of the female;
• Systemic contraceptives (combined or progesterone only).
16. Subject is able to understand and comply with protocol requirements and instructions. |
|
| E.4 | Principal exclusion criteria |
1. Any clinically relevant abnormality, other than ITP, identified on the screening examination, or any other medical condition or circumstance, which in the opinion of the investigator makes the subject unsuitable for participation in the study or suggests another diagnosis.
2. History of malignancy. NOTE: Patients with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma, are eligible.
3. History of arterial or venous thrombosis (stroke, transient ischemic attack, myocardial infarction, deep vein thrombosis or pulmonary embolism).
4. Any prior history of arterial or venous thrombosis AND at least two of the following risk factors: Factor V Leiden, hormone replacement therapy, systemic contraception (containing estrogen), smoking, diabetes, hypercholesterolemia, medication for hypertension or cancer.
5. Pre-existing cardiac disease (including congestive heart failure, and arrhythmia requiring treatment), or clinically significant findings on resting 12-lead ECG at screening.
6. Female subjects who are nursing or pregnant (positive serum or urine beta-human chorionic gonadotrophin (beta-hCG) pregnancy test) at screening or pre-dose on Day 1.
7. History of alcohol/drug abuse.
8. Treatment with an investigational drug within 30 days or five half-lives (whichever is longer) preceding the first dose of study medication.
9. Subject treated with aspirin, aspirin-containing compounds, salicylates, anti-coagulants, quinine or non-steroidal anti-inflammatories (NSAIDs) for > 3 consecutive days within 2 weeks of the study start and until the end of the study.
10. Consumption of any herbal or dietary supplements, excluding vitamin or mineral supplements, within 1 week of the study start (see Section 9.1.1. for instructions for taking calcium and vitamin supplements). Subjects that have consumed rosuvastatin or pravastatin within 1 week of the first dose of study medication and/or will require these medications during the study period.
11. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
12. All subjects with secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, antiphospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence for active hepatitis at the time of subject screening. If a potential subject has no clinical history that would support HIV infection or hepatitis infection, no further laboratory screening is necessary; however, standard medical practice would suggest further evaluation of patients who have risk factors for these infections.
13. A subject is planning to have cataract surgery.
14. In France, a subject is neither affiliated with nor a beneficiary of a social security category. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
| Safety and tolerability parameters including, clinical laboratory tests, ocular examinations, and frequency of all adverse events |
|
| 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 | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | Information not present in EudraCT |
| E.6.11 | Pharmacogenomic | Yes |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
|
| 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) | No |
| E.7.4 | Therapeutic use (Phase IV) | Yes |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | No |
| E.8.1.2 | Open | Yes |
| 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.8.1.7.1 | Other trial design description |
|
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | No |
| 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.8.5 | The trial involves multiple Member States | Yes |
| 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 | Information not present in EudraCT |
| 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 | 1 |
| 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 | 1 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
Print
