E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
immune thrombocytopenia (ITP) |
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E.1.1.1 | Medical condition in easily understood language |
immune thrombocytopenia (ITP) |
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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 | 23.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10083842 |
E.1.2 | Term | Immune thrombocytopenia |
E.1.2 | System Organ Class | 10005329 - Blood and lymphatic system disorders |
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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 demonstrate that the addition of ianalumab (either dose) to standard of care, eltrombopag, prolongs Time to Treatment Failure (TTF) compared to eltrombopag alone in participants with primary ITP who have had an insufficient response to or relapsed after first-line treatment with corticosteroids |
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E.2.2 | Secondary objectives of the trial |
1. To assess quality, time to and duration of response in each treatment arm 2. To assess the rate of participants who successfully taper and discontinue eltrombopag in each treatment arm 3. To assess the incidence and severity of bleeding in each treatment arm 4. To assess the need for rescue treatments in each treatment group 5. To evaluate treatment effects on ITP related symptoms, functioning, and health-related quality of life (HFRQoL) 6. To assess B-Cell levels and immunoglobulin (lg) levels 7. To assess ianalumab pharmacokinetics (PK) 8. To assess the immunogenicity of ianalumab |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female patients aged 18 years and older on the day of signing the informed consent. 2. A signed informed consent must be obtained prior to participation in the study. 3. A diagnosis of primary ITP, with insufficient response to, or relapse after a first-line corticosteroid therapy± IVIG. 4. Patients with platelet count <30 G/L, for whom eltrombopag is clinically indicated as per physician's discretion and with no contraindication to receive eltrombopag. Other protocol defined criteria may apply |
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E.4 | Principal exclusion criteria |
1. ITP patients who received second-line ITP treatments (other than corticosteroid therapy± IVIG) including splenectomy. However, patients exposed to thrombopoietin receptor agonists (TPO-RAs) for a limited time (max one week) before screening are eligible. 2. Patients with key lab abnormalities and patients with Evans syndrome or any other cytopenia (patients with low grade anemia related to bleeding or iron deficiency are eligible) 3. Patients with history of clinically significant hematological disorders, or with marked altered hematologic parameters 4. Patients with current or history of life-threatening bleeding 5. Patient that are Human Immunodeficiency Virus (HIV), Hepatitis C Virus (HCV), Hepatitis B surface Antigen (HBsAg)/ Hepatitis B core antibody (HBcAB)-positive. HBcAb positive patients can be enrolled if HBsAg negative, HBV negative, HBV DNA negative, no pre-existing liver fibrosis is present and antiviral prophylaxis is given. 6. Patients with known active or uncontrolled infection requiring systemic treatment during screening period 7. Patients with hepatic impairment 8. Patients with concurrent coagulation disorders and/or receiving antiplatelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acide(≤150 mg daily) 9. Female patients who are pregnant or nursing Other protocol defined criteria may apply |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomization date until the first of the following events indicative of treatment failure: -platelet count below 30 G/L -start of a new ITP treatment -need for a rescue treatment -ineligibility to taper or inability to discontinue eltrombopag -death |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Randomization to end of study (up to 39 months after randomization of last participant) |
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E.5.2 | Secondary end point(s) |
1. Percentage of participants with any platelet count of at least 100 G/L in the absence of rescue treatment or new ITP treatment 2. Percentage of participants with any platelet count of at least 50 G/L in the absence of rescue treatment or new ITP treatment 3. Percentage of participants with a best response rate by either response or complete response 4. Time from randomization to date of first response and time from randomization to date of first complete response 5. Time from achievement of response to treatment failure 6. Stable response in each treatment group 7. Time from achievement of complete response to loss of complete response 8. Probability to be treatment failure-free (as defined for the primary efficacy endpoint) after the end of treatment period 9. Percentage of participants reporting bleeding events according to WHO bleeding scale 10. Number of participants who are in need of rescue treatment in each treatment arm 11. Percentage of participants who are in need of rescue treatment 12. The Patient-Reported Outcomes Measurement Information System (PROMIS) Short Form v1.0 Fatigue 13a includes 13 items that assess fatigue in adults. 13. The ITP-PAQ is a 44 item scale for measuring HRQoL in adults with ITP across ten scales: Symptoms, BotherPhysical Health, Fatigue/Sleep, Activity, Fear, Psychological Health, Work, Social Activity, Women's Reproductive Health, overall Qol. Each item is rated on a Likert type scale. Each scale is scored from O to 100. Higher scores represent better HRQoL 14. Change from baseline in the frequency (percentage within CD45) and absolute number of CD19+ B-cell counts 15. Time to B-cell recovery defined as ≥80% of baseline or ≥ 50 cells/µL 16. Change from baseline in immunoglobulin levels 17. AUClast: Area under the curve from time zero to the last measurable concentration sampling time (tlast) AUCtau: Area under the curve calculated to the end of a dosing interval (tau) 18. Cmax: Maximum (peak) observed plasma, blood, serum or other body fluid drug concentration 19. Tmax: Time to reach maximum (peak) observed plasma, blood, serum or other body fluid drug concentration 20. Racc: Accumulation ratio calculated using AUC values obtained after the last and first dose 21. Anti-drug antibodies (ADA) will be evaluated in samples collected from all participants assessing the immunogenicity of ianalumab |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-3,5, 7,9-11,14-16: Randomization to end of study (up to 39 months after randomization of last participant) 4: Time from randomization up to the longest observed treatment period duration 6: At 6 months and 1 year 8: End of planned treatment period 12, 13: From screening (baseline) until end of study (up to 39 months after randomization of last participant) 17-21: After the first and last dose of study medication
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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 | 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 | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
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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) | 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 | 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.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 28 |
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 |
Argentina |
Malaysia |
Philippines |
Singapore |
Taiwan |
Australia |
China |
India |
Japan |
Korea, Republic of |
Mexico |
Thailand |
United Kingdom |
United States |
Austria |
Belgium |
Czechia |
France |
Germany |
Hungary |
Italy |
Netherlands |
Norway |
Romania |
Spain |
Türkiye |
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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
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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 | 4 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 13 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 2 |
E.8.9.2 | In all countries concerned by the trial days | 15 |