E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
Urticaire chronique spontanée (UCS) |
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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] - Skin and Connective Tissue Diseases [C17] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072757 |
E.1.2 | Term | Chronic spontaneous urticaria |
E.1.2 | System Organ Class | 10040785 - Skin and subcutaneous tissue disorders |
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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 |
Epoch 1: Randomized withdrawal period To assess the efficacy of remibrutinib in CSU participants with a UAS7<16 at Week 52 in the prior core study with respect to time to first of the three events: relapse or study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication up to Week 24 compared to placebo |
Epoch 1 : Période de retrait aléatoire Evaluer par rapport au placebo l'efficacité du remibrutinib (25 mg bid) chez les patients atteints d’UCS avec un score UAS7 (pour Weekly Urticaria Activity Score, score hebdomadaire d’activité de l’urticaire) < 16 à la semaine 52 de l'étude principale précédente en ce qui concerne le délai jusqu’au 1er des trois événements : • rechute ou • arrêt du traitement à l’étude en raison d'un manque d'efficacité ou • prise de médicaments interdits fortement confondants jusqu'à la semaine 24. |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term safety and tolerability of remibrutinib |
Evaluer l’innocuité et la tolérance à long terme du remibrutinib 25 mg bid |
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E.2.3 | Trial contains a sub-study | Yes |
E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
The study includes additional optional biomarker research components. Samples will be stored and analyzed depending on results of other biomarker assessments in this study, the overall study outcome, and/or other studies. Serum samples will be collected for autoantibodies assessment and the assessment of additional exploratory biomarkers, e.g., soluble FcR1. These serum samples may be used to better understand disease heterogeneity and for the identification of efficacy and/or stratification markers. Additionally, the effect of remibrutinib exposure on antibody titers may be assessed. Detailed descriptions of the assays will be included in the bioanalytical data reports. Biomarkers may also include targeted single or multiplex biomarkers panels (autoantibody, protein, peptide or metabolite biomarkers) or hypothesis-free platforms (autoantibody, protein, peptide and metabolite biomarkers). |
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E.3 | Principal inclusion criteria |
- Written informed consent must be obtained before any assessment is performed. - Male and female, adult participants ≥18 years of age. - Participants who successfully completed the preceding core studies CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 or CLOU064A2305 according to the respective protocols. - Willing and able to adhere to the study protocol and visit schedule. |
Les patients éligibles pour inclusion dans cette étude doivent satisfaire à tous les critères suivants : • Obtention du consentement éclairé écrit avant toute évaluation. • Patients adultes de sexe masculin ou féminin âgés de ≥ 18 ans. • Patients ayant terminé avec succès les précédentes études principales CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 ou CLOU064A2305 selon les protocoles respectifs. • Avoir la volonté et être en mesure de respecter le protocole d'étude et le calendrier des visites. |
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E.4 | Principal exclusion criteria |
- Other diseases with symptoms of urticaria or angioedema, including but not limited to urticarial vasculitis, urticaria pigmentosa, erythema multiforme, mastocytosis, hereditary angioedema, or drug-induced urticaria. - Any other skin disease associated with chronic itching that might influence in the investigator’s opinion the study evaluations and results, e.g., atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus or psoriasis. - Evidence of clinically significant cardiovascular (such as but not limited to myocardial infarction, unstable ischemic heart disease, NYHA (New York heart association) Class III/IV left ventricular failure, arrhythmia and uncontrolled hypertension within 12 months prior to enrollment), neurological, psychiatric, pulmonary, renal, hepatic, endocrine, metabolic, hematological disorders, gastrointestinal disease or immunodeficiency that, in the investigator's opinion, would compromise the safety of the participant, interfere with the interpretation of the study results or otherwise preclude participation or protocol adherence of the participant. - Significant bleeding risk or coagulation disorders. - History of gastrointestinal bleeding, e.g., in association with use of nonsteroidal anti-inflammatory drugs (NSAID), that was clinically relevant. - Requirement for anti-platelet medication, except for acetylsalicylic acid up to 100 mg/d or clopidogrel up to 75 mg/d. The use of dual anti-platelet therapy (e.g., acetylsalicylic acid + clopidogrel) is prohibited. - Requirement for anticoagulant medication (for example, warfarin or Novel Oral Anti-Coagulants (NOACs)). - History or current hepatic disease including but not limited to acute or chronic hepatitis, cirrhosis or hepatic failure or Aspartate Aminotransferase (AST)/ Alanine Aminotransferase (ALT) levels of more than 1.5 x upper limit of normal (ULN) or International Normalized Ratio (INR) of more than 1.5 at the last 2 available visits of the preceding core study.
Other protocol-defined exclusion criteria may apply. |
Risque significatif de saignements ou troubles de la coagulation • Antécédents d'hémorragie gastro-intestinale. • Besoin d'un médicament antiplaquettaire. • Besoin d'un traitement anticoagulant. • Antécédents ou maladie hépatique actuelle. • Preuve d’affections cliniquement significatives d’ordre cardiovasculaire, neurologique, psychiatrique, pulmonaire, rénal, hépatique, endocrinien, métabolique, hématologique, maladie gastro-intestinale ou immunodéficience qui, de l'avis de l'investigateur, seraient susceptibles de compromettre la sécurité du patient, d’interférer l'interprétation des résultats de l'étude ou autrement excluraient la participation au protocole ou son respect par le patient |
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E.5 End points |
E.5.1 | Primary end point(s) |
Time to first composite event (i.e., relapse (UAS7≥16), study treatment discontinuation due to lack of efficacy or intake of strongly confounding prohibited medication) during the randomized withdrawal period |
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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) |
Occurrence of treatment-emergent (serious and non-serious) adverse events during the extension study |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
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 | 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 | Yes |
E.8.1.7.1 | Other trial design description |
Randomized withdrawal period (placebo-controlled) and open-label extension (single arm) |
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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 | 2 |
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 | 6 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 84 |
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 |
Brazil |
Canada |
China |
Colombia |
India |
Japan |
Korea, Republic of |
Malaysia |
Mexico |
Singapore |
South Africa |
Taiwan |
Thailand |
United States |
Viet Nam |
Austria |
France |
Poland |
Bulgaria |
Spain |
Switzerland |
Czechia |
Germany |
Italy |
Denmark |
Hungary |
Russian Federation |
Slovakia |
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 | 4 |
E.8.9.1 | In the Member State concerned months | 1 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 22 |