| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
Chronic Idiopathic Thrombocytopenic Purpura
Púrpura Trombocitopénica Idiopática Crónica |
|
| 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 | 10021245 |
| E.1.2 | Term | Idiopathic thrombocytopenic purpura |
|
| 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 assess the efficacy of eltrombopag, relative to placebo, in achieving a platelet count ?50Gi/L at any time during a 6 week treatment period when administered to previously treated pediatric subjects with chronic ITP. |
|
| E.2.2 | Secondary objectives of the trial |
?To describe the safety and tolerability of eltrombopag when administered for 24 weeks
?To characterize the PK profile of eltrombopag in pediatric subjects
?To describe the efficacy of eltrombopag in achieving platelet counts ? 50Gi/L when administered for 24 weeks
?To describe the effect of eltrombopag on reduction and/or interruption of concomitant ITP therapies, when administered for 24 weeks
?To describe the effect of eltrombopag on the need for rescue ITP medication when administered to previously treated pediatric subjects
?To assess the impact of eltrombopag on the incidence and severity of bleeding symptoms when administered in previously treated pediatric patients
?To evaluate the impact of eltrombopag on the quality of life of previously treated pediatric patients |
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1. Subjects between 1 year and <18 years of age at Day 1.
2. Written informed consent from subject?s guardian and accompanying informed assent from subject (for children over 6 years old).
3. Confirmed diagnosis of chronic ITP, according to the American Society of Hematology / British Committee for Standards in Haematology (ASH/BCSH) guidelines [George, 1996; BCSH, 2003]. In addition, a peripheral blood smear or bone marrow examination should support the diagnosis of ITP with no evidence of other causes of thrombocytopenia.
4. Subjects who are refractory or have relapsed after at least one prior ITP therapy or are not eligible, for a medical reason, for other treatments.
5. Day 1 (or within 48 hours prior) platelet count <30 Gi/L.
6. Previous therapy for ITP with immunoglobulins (IVIg and anti-D) must have been completed at least 2 weeks prior to Day 1 or have been clearly ineffective.
7. Subjects treated with concomitant ITP medication (e.g. corticosteroids or azathioprine) must be receiving a dose that has been stable for at least 4 weeks prior to Day 1.
8. Previous treatment for ITP with splenectomy, rituximab and cyclophosphamide must have been completed at least 4 weeks prior to Day 1 or have clearly been ineffective.
9. Subjects must have prothrombin time (PT/INR) and activated partial thromboplastin time (aPTT) within 80 to 120% of the normal range.
10. Subjects must have a complete blood count (CBC) not suggestive of another hematological disorder.
11. The following clinical chemistries for the subjects MUST NOT exceed the upper limit of normal (ULN) reference range by more than 20%: creatinine, ALT, AST, total bilirubin, and alkaline phosphatase. In addition, total albumin must not be below the lower limit of normal (LLN) by more than 10%.
12. For subjects of child-bearing potential (after menarche): subject must not be sexually active or is practicing an acceptable method of contraception (documented in chart). Female subjects (or female partners of male subjects) must use one of the following highly effective methods of contraception (i.e., Pearl Index <1.0%) 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);
? Systemic contraceptives (combined or progesterone only). |
|
| 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 primary diagnosis (e.g. thrombocytopenia is secondary to another disease).
2. Concurrent or past malignant disease, including myeloproliferative disorder.
3. Subjects who are not suitable for continuation of their current therapy for at least 7 additional weeks.
4. Treatment with an investigational drug within 30 days or 5 half-lives (whichever is longer) preceding Day 1.
5. History of platelet agglutination abnormality that prevents reliable measurement of platelet counts.
6. Diagnosis of secondary immune thrombocytopenia, including those with laboratory or clinical evidence of HIV infection, anti-phospholipid antibody syndrome, chronic hepatitis B infection, hepatitis C virus infection, or any evidence of active hepatitis at the time of subject screening.
7. Subject with Evans syndrome (autoimmune thrombocytopenia and autoimmune hemolysis).
8. Subjects with known inherited thrombocytopenia (e.g. MYH-9 disorders)
9. Subjects treated with drugs that affect platelet function (including but not limited to aspirin, clopidogrel and/or NSAIDs) or anti-coagulants for >3 consecutive days within 2 weeks of Day 1.
10. Subjects who have previously received eltrombopag or any other thrombopoietin receptor agonist.
11. For female subjects who have reached menarche status, an inability or unwillingness to provide a blood or urine specimen for pregnancy testing.
12. Female subjects who are pregnant or lactating.
13. 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) |
Proportion of subjects achieving platelet counts ?50Gi/L at least once between days 8 and 43 of the randomized period of the study.
Proporción de sujetos que logren un recuento de plaquetas ? 50 Gi/l al menos en una ocasión entre los días 8 y 43 del período aleatorizado del estudio |
|
| 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 | Yes |
| E.6.10 | Pharmacogenetic | Yes |
| E.6.11 | Pharmacogenomic | Yes |
| 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) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| 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 | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| 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) | 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 | 3 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 20 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
| 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 | 0 |
| E.8.9.1 | In the Member State concerned days | 0 |
| 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 | 0 |
| E.8.9.2 | In all countries concerned by the trial days | 0 |
Print
