| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
|
| E.1.1.1 | Medical condition in easily understood language |
|
| 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 | 23.0 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10050245 |
| E.1.2 | Term | Autoimmune thrombocytopenia |
| E.1.2 | System Organ Class | 100000004851 |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 22.1 |
| E.1.2 | Level | LLT |
| E.1.2 | Classification code | 10036735 |
| E.1.2 | Term | Primary thrombocytopenia |
| E.1.2 | System Organ Class | 100000004851 |
|
| 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 |
|
| E.2.2 | Secondary objectives of the trial |
assess 1.duration of sustained remission after treatment discontinuation
by M12 and 24
2.proportion of patients maintaining a sustained remission after treatment discontinuation until M24 3.ability of eltrombopag to induce early response by month 1 4.ability of eltrombopag to induce a recovery response, in case of loss of response during or after tapering of eltrombopag until M 24 5.platelet count from baseline and every 3M until M24 6.ability of eltrombopag to maintain platelet count ≥ 30×109/L within 12M and every 3M until 24M 7.evaluate patient-Health Related outcome measures for health-related quality of life (fatigue level of the patients through FACIT) & FACT-Th6 and SF-36v2 questionnaires from baseline and every 3M to 24M and end of treatment/ to explore 8.overall impact of side effects on treatment via the GP5 at baseline,M12, and end of treatment 9.treatment satisfaction with TSQM-9 at baseline, M12, and end of treatment 10.evaluate the safety and tolerability of eltrombopag |
|
| 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
|
|
| E.4 | Principal exclusion criteria |
1. ITP patients previously treated with any ITP second-line therapies,
thrombopoietin receptor (TPO-R) agonists for ITP, except steroids /
IVIG
2. Patients who relapsed more than one year after the end of first-line
full course of steroid therapy
3. Patients with a diagnosis of secondary thrombocytopenia
4. Patients who are unable to participate in assessments/biological
studies
5. Patients who have life threatening bleeding complications per
investigator discretion
6. Patients who had a deep vein thrombosis or arterial thrombosis in the
6 months preceding enrollment
7. Presence of moderate to severe impaired renal function as indicated
by any or all of the following criteria:
Creatinine clearance < 45 mL/min as calculated using Cockcroft-Gault
formula
Serum creatinine > 1.5 mg/dL
8. Total bilirubin > 1.5 × upper limit of normal (ULN)
9. Aspartate transaminase (AST) > 3.0 × ULN
10. Alanine transaminase (ALT) > 3.0 × ULN
11. Subjects who are human immune deficiency virus (HIV), hepatitis C
virus (HCV), hepatitis B surface antigen (HBsAg) positive
12. Subjects with hepatic impairment (Child-Pugh score > 5)
13. Subjects who have active malignancy
14. 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
15. History or current diagnosis of cardiac disease indicating significant
risk of safety for subjects participating in the study
16. Subjects with known active or uncontrolled infections not responding
to appropriate therapy
17. Subjects with evidence of current alcohol/drug abuse
18. Women of child-bearing potential and sexually active males unwilling
to use adequate contraception during the study
19. 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 |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
Proportion of patients with sustained remission (R) by month 12 where
sustained remission is defined as:
reach platelet count ≥ 100×109/L (complete response [CR]) and then
maintain platelet counts around 100×109/L for 2 months (no counts
below 70×109/L) AND then
taper off the drug until treatment discontinuation while,
maintain platelet count ≥ 30×109/L in the absence of bleeding (no
bleeding AEs) or use of any rescue therapy until month 12.
|
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
| E.5.2 | Secondary end point(s) |
1a. Median duration of sustained remission (weeks) counted from last
dose of eltrombopag to month 12 for patients with sustained remission
(R)
1b. Estimated median duration of sustained remission (weeks) by month
24 for patients who are in sustained remission (R) at month 12 and
enter 12 months follow-up period using Kaplan-Meier method
1c. Estimated median duration of sustained remission (weeks) by month
24 for all patients using Kaplan-Meier method.
2. Proportion of sustained remission (R) patients at months 15, 18, 21,
and 24.
3. Number (%) of patients with platelet count ≥ 50×109/L at least once
by month 1 (first month) without bleeding and no rescue therapy
4. Number (%) of patients with at least one platelet count ≥ 30×109/L
after eltrombopag is re-introduced, in case of loss of response (<
30×109/L and/or bleeding event) without bleeding and no rescue
therapy by month 12 and 24
5. Absolute and relative change in platelet count from baseline to 3, 6,
9,12, 15, 18, 21, and 24 months and end of treatment
6. Number (%) of patients who maintain a platelet count ≥ 30×109/L
from the first time of reaching that level to month 3, 6, 9, 12, 15, 18, 21,
24, and end of treatment without bleeding and no rescue therapy
7. The analysis of HRQoL parameters; fatigue level of the patients
through FACIT & FACT-Th6, SF-36v2 questionnaires. Change in scores
from baseline to month 3, 6, 9, 12, 15, 18, 21, 24, and end of treatment
8. Overall change from baseline to month 12 and end of treatment will
be assessed
9. Overall change from baseline to month 12 and end of treatment will
be assessed
10. Number (%) and severity of patients with AEs, serious AEs (SAEs),
AEs leading to discontinuation, AEs leading to dose adjustments, AEs of
special interest. Change from baseline in vital signs and clinical
laboratory tests |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
1a. 12 months
1b. 24 months
1c. 24 months
2. at months 15, 18, 21 and 24
3. 1 month
4. 12 and 24 months
5. from baseline to 3, 6, 9,12, 15, 18, 21, and 24 months and end of
treatment
6.from the first time of reaching required platelet level to month 3, 6, 9,
12, 15, 18, 21, 24, and end of treatment
7. from baseline to month 3, 6, 9, 12, 15, 18, 21, 24, and end of
treatment
8. from baseline to month 12 and end of treatment
9. from baseline to month 12 and end of treatment
10. from baseline |
|
| 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
| Yes |
| E.8.4 | The trial involves multiple sites in the Member State concerned | No |
| 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 |
| Brazil |
| Chile |
| Japan |
| Mexico |
| Oman |
| Russian Federation |
| Saudi Arabia |
| Turkey |
| United States |
| Austria |
| France |
| Germany |
| Greece |
| Italy |
| Spain |
| Switzerland |
| United Kingdom |
|
| 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
|
Study completion is defined as when the last patient finishes their end
of follow-up / month 24 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. |
|
| 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 | 22 |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 3 |
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