E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Primary Immune thrombocytopenia (ITP) |
thrombopénie immunologique primaire |
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E.1.1.1 | Medical condition in easily understood language |
immune thrombocytopenia (ITP) |
thrombopénie immunologique |
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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 corticosteroids alone in participants with primary ITP who responded to corticosteroids (+/-IVIG) prior to randomization
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Démontrer que l’ajout du ianalumab (quelle que soit la dose) à un traitement de première ligne par corticostéroïdes prolonge le temps jusqu’à l’échec du traitement par rapport à des corticostéroïdes seuls chez des patients atteints de TI primaire ayant présenté une réponse aux corticostéroïdes (avec ou sans immunoglobulines par voie intraveineuse) avant la randomisation. |
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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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- Evaluer la qualité de la réponse, le temps pour obtenir une réponse complète (RC) et la durée de cette réponse dans chaque bras de traitement. - Evaluer l’incidence et la sévérité des saignements dans chaque bras de traitement -Evaluer le besoin d’un traitement de secours dans chaque bras de traitement - Evaluer les effets du traitement sur les symptômes en lien avec la TI primaire, les capacités fonctionnelles et la qualité de vie liée à la santé - Evaluer les taux de cellules B et d’immunoglobulines dans chaque bras de traitement - Evaluer la pharmacocinétique (PK) du ianalumab - Evaluer l’immunogénicité du 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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1a. Obtention du consentement éclairé avant la participation à l’étude 2a. Patients de sexe masculin ou féminin, âgés d’au moins 18 ans le jour de la signature du formulaire de consentement 3a. Patients atteints de TI primaire diagnostiquée dans les 3 mois précédant l’instauration d’un traitement de première ligne (corticostéroïdes, immunoglobulines intraveineuses) 4. Nombre de plaquettes < 30 G/l avant l’instauration de tout traitement de première ligne de la TI primaire (corticostéroïdes, immunoglobulines par voie intraveineuse) 5. Réponse au traitement (nombre de plaquettes ≥ 50 G/l) par corticostéroïdes (avec ou sans immunoglobulines par voie intraveineuse) à tout moment avant la randomisation. Remarque : le nombre de plaquettes déterminé dans les 7 jours suivant une transfusion de plaquettes ne sera pas considéré comme une réponse. |
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E.4 | Principal exclusion criteria |
-Evans syndrome or any other cytopenia -Current life-threatening bleeding -Previous ITP treatment, including splenectomy, except for corticosteroids and/or IVIG for up to 28 days before randomization. -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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1. Syndrome d’Evans ou autre cytopénie 2. Présence d’hémorragie menaçant le pronostic vital 3a. Traitement antérieur de la TI primaire, y compris une splénectomie, à l’exception des corticostéroïdes et/ou des immunoglobulines par voie intraveineuse jusqu’à 28 jours précédant la andomisation 4a. Thérapie antérieure de déplétion des cellules B (par ex. rituximab) 6a. Nombre absolu de neutrophiles < 1,0 G/l à la randomisation 7a. Troubles concomitants de la coagulation et/ou traitement concomitant par antiagrégant plaquettaire ou anticoagulant, sauf en cas de traitement par aspirine à faible dose (se référer à la section sur les médicaments interdits en Section 6.8.2 du protocole) |
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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. Proportion of participants with bleeding events overall and by WHO bleeding scale severity 6. Number and proportion of participants receiving rescue treatment 7. Cumulative dose/duration of steroids exposure 8. Change from baseline on total scores of the PROMIS SF v1.0 Fatigue 13a 9. Change from baseline in ITP-PAQ domain scores of Symptoms, Fatigue, Bother, Activity 10. Change from baseline in frequency and absolute number of CD19+ B cell counts 11. Time to first occurrence of B-cell recovery 12. Change from baseline in inmmunoglobulins 13. PK parameters: AUClast, AUCtau - PK parameters: Cmax - PK parameters: Tmax - PK parameters: Accumulation ratio Racc 14. 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 |
1-6, 10-12 Randomization to end of study (up to 39 months after randomization of last patient) 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 | 7 |
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 |
Australia |
China |
Hong Kong |
India |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Singapore |
Thailand |
United States |
Viet Nam |
Austria |
France |
Romania |
Spain |
Czechia |
Germany |
Italy |
Belgium |
Hungary |
Norway |
Turkey |
United Kingdom |
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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 | 1 |
E.8.9.1 | In the Member State concerned days | 9 |
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 |