E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
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E.1.1.1 | Medical condition in easily understood language |
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E.1.1.2 | Therapeutic area | Diseases [C] - Blood and lymphatic diseases [C15] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10050245 |
E.1.2 | Term | Autoimmune thrombocytopenia |
E.1.2 | System Organ Class | 100000004851 |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10036735 |
E.1.2 | Term | Primary thrombocytopenia |
E.1.2 | System Organ Class | 100000004851 |
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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 assess ability of eltrombopag to induce sustained remission by month 12 in ITP subjects who relapsed or failed to respond to first-line steroid treatment |
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E.2.2 | Secondary objectives of the trial |
1. To assess the duration of sustained remission after treatment discontinuation
2. To assess the ability of eltrombopag to induce early response by month 1
3. To assess the ability of eltrombopag to induce a recovery response, in case of loss of response during or after tapering of eltrombopag
4. To quantify the platelet count from baseline to 3, 6, 9, 12 months
5. To assess the ability of eltrombopag to maintain platelet count ≥ 30×109/L within 12 months
6. To evaluate patient-Health Related outcome measures for health-related quality
of life (fatigue level of the subjects through FACIT) & FACT-Th6 and SF-36v2 questionnaires
7. To explore the overall impact of side effects on treatment via the GP5 at baseline and EOS
8. To explore treatment satisfaction with TSQM-9
9. To evaluate the safety and tolerability of eltrombopag |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study
2. Subjects ≥ 18 years old
3. Subjects with a confirmed diagnosis of primary ITP, who are not responsive or in relapse after a first line of steroid therapy ± intravenous immunoglobulin (IVIG) (used as a rescue therapy)
4. Platelet count < 30×109/L and assessed as needing treatment (per physician’s discretion
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E.4 | Principal exclusion criteria |
1. ITP subjects previously treated with any ITP second-line therapies, thrombopoietin receptor (TPO-R) agonists for ITP, except steroids / IVIG
2. Subjects who relapsed more than one year after the end of first-line full course of steroid therapy
3. Subjects with a diagnosis of secondary thrombocytopenia
4. Subjects who have life threatening bleeding complications per investigator discretion
5. Subjects who had a deep vein thrombosis or arterial thrombosis in the 6 months preceding enrollment
6. Serum creatinine ≥ 1.5 mg/dL
7. Total bilirubin > 1.5 × upper limit of normal (ULN)
8. Aspartate transaminase (AST) > 3.0 × ULN
9. Alanine transaminase (ALT) > 3.0 × ULN
10. Subjects who are human immune deficiency virus (HIV), hepatitis C virus (HCV), hepatitis B surface antigen (HBsAg) positive
11. Subjects with hepatic impairment (Child-Pugh score > 5)
12. Subjects who have active malignancy
13. Subjects with any serious and/or unstable pre-existing medical, psychiatric disorder or other conditions that could interfere with subject’s safety, obtaining informed consent or compliance with the study procedures per investigator discretion
14. History or current diagnosis of cardiac disease indicating significant risk of safety for subjects participating in the study
15. Subjects with known active or uncontrolled infections not responding to appropriate therapy
16. Subjects with evidence of current alcohol/drug abuse
17. Women of child-bearing potential and sexually active males unwilling to use adequate contraception during the study
18. Female subjects who are nursing or pregnant (positive serum or urine B-human chorionic gonadotrophin (B-hCG) pregnancy test) at screening or pre-dose on Day 1
Other protocol-defined inclusion/exclusion criteria may apply
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E.5 End points |
E.5.1 | Primary end point(s) |
Percentage of participants with sustained remission (R) by 12 months
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
1. Median duration of sustained remission
2. Percentage of participants with platelet count ≥ 50×109/L
3. Percentage of participants with at least one platelet count ≥ 30×109/L after eltrombopag is re-introduced without bleeding and no rescue medication
4. Absolute and relative change in platelet count from baseline to various time points
5. Percentage of participants who maintain a platelet count ≥ 30×109/L without bleeding and no rescue medication
6. Change from baseline in Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionaire
7. Change from baseline in Functinal Assessment of Cancer Therapy- Thrombocytopenia (FACT-Th6) questionnaire
8. Change from baseline in Short Form 36 Health Survey (SF-36v2) questionnaire
9. Overall change from baseline of the overall impact of side effects on treatment via Functional Assessment of Cancer Therapy-G (GP5)
10. Overall change of treatment satisfaction using Treatment Satisfaction Questionnaire (TSQM-9) |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1. 12 months
2. by 1 month
3. 12 months
4. Baseline 3, 6, 9, 12 months
5. From first time of reaching the level to 3, 6, 9, 12 months
6.Baseline to 3, 6, 9, 12 months
7. Baseline to 3, 6, 9, 12 months
8. Baseline to 3, 6, 9, 12 months
9. Baseline, 12 months or end of study
10. Baseline, 12 months or end of study |
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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 | Yes |
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) | 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 | No |
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.8.2 | 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.8.4.1 | 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 | 37 |
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 | No |
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 |
Austria |
Brazil |
Chile |
France |
Germany |
Greece |
Italy |
Japan |
Mexico |
Norway |
Oman |
Russian Federation |
Saudi Arabia |
Spain |
Switzerland |
Turkey |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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
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Study completion is defined as when the last subject finishes their EOS visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the Investigator, or in the event of an early study termination decision, the date of that decision |
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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 | 8 |
E.8.9.1 | In the Member State concerned days | 17 |
E.8.9.2 | In all countries concerned by the trial years | 2 |