E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary 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.1.3 | Condition being studied is a rare disease | No |
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 first-line corticosteroids prolongs Time to Treatment Failure (TTF) compared to the control arm (placebo + corticosteroids) in participants with primary ITP who responded to corticosteroids (+/-IVIG) prior to randomization
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E.2.2 | Secondary objectives of the trial |
- To assess quality of response, time to and duration of complete response in each treatment group - To assess the incidence and severity of bleeding in each treatment arm - To assess the need of rescue treatment in each treatment group - To evaluate treatment effects on ITP related symptoms, functioning, and health-related quality of life (HRQoL) - To assess B-cell and immunoglobulin levels in each treatment group - To assess ianalumab pharmacokinetics (PK) - To assess the immunogenicity of ianalumab
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
-Signed informed consent prior to participation in the study. -Male or female participants aged 18 years and older on the day of signing informed consent -Primary ITP diagnosed within 3 months before initiating first-line ITP therapy (corticosteroids, IVIG) -Platelet count below 30 G/L before starting any first-line ITP therapy (corticosteroids, IVIG) - Response (platelet count >=50 G/L) to corticosteroids (+/- IVIG) at any time prior to randomization. Note: Platelet count measured within 7 days of platelet transfusion will not be considered as response.
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E.4 | Principal exclusion criteria |
-Evans syndrome or any other cytopenia (patients with anemia related to bleeding iron deficiency are eligible) -Current life-threatening bleeding -Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG initiated as first-line therapy for up 28 days before randomization/or IVIG given prior to confirmed diagnosis of primary ITP. -Prior use of B-cell depleting therapy (e.g., rituximab) -Absolute neutrophil count below 1.0 G/L at randomization -Participants with concurrent coagulation disorders and/or receiving anti-platelet or anticoagulant medication with an exemption of low dose of acetylsalicylic acid
Other protocol-defined Inclusion/Exclusion may apply.
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E.5 End points |
E.5.1 | Primary end point(s) |
Time from randomization to treatment failure (TTF) defined as platelet count below 30 G/L, need for a rescue treatment, start of a second-line therapy or 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 patient) |
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E.5.2 | Secondary end point(s) |
1. Complete Response (CR) rate in each treatment group 2. Response (R) rate in each treatment group 3. Time to response / complete response in each treatment group 4. Duration of response in each treatment group 5. Stable response in each treatment group 6. Proportion of participants with bleeding events overall and by WHO bleeding scale severity 7. Number and proportion of participants receiving rescue treatment 8. Cumulative dose/duration of steroids exposure 9. Change from baseline on T-scores of the PROMIS SF v1.0 Fatigue 13a 10. Change from baseline in ITP-PAQ domain scores of Symptoms, Fatigue, Bother, Activity 11. Change from baseline in frequency and absolute number of CD19+ B cell counts 12. Time to first occurrence of B-cell recovery 13. Change from baseline in inmmunoglobulins 14. PK parameters: AUClast, AUCtau - PK parameters: Cmax - PK parameters: Tmax - PK parameters: Accumulation ratio Racc 15. Incidence and titer of anti-ianalumab antibodies in serum (ADA assay) over time
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1-4, 6-7, 10-12 Randomization to end of study (up to 39 months after randomization of last patient) 5: At 6 months and 1 year 7-9 From screening (baseline) till end of study (up to 39 months after randomization of last patient) 13: After the first and last dose of study medication 14: Up to end of study (up to 39 months after randomization of last patient)
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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 | Yes |
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 |
- Patient reported outcomes - Immunogenicity |
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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 | 4 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 42 |
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 |
Singapore |
Hong Kong |
Australia |
China |
India |
Japan |
Korea, Republic of |
Mexico |
Thailand |
United Kingdom |
United States |
Viet Nam |
Austria |
Belgium |
Czechia |
France |
Germany |
Hungary |
Italy |
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 | 5 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 18 |
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 |