E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
Urticaria crónica espontánea (UCE). |
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E.1.1.1 | Medical condition in easily understood language |
Chronic Hives |
Habones crónicos |
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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 |
Etapa 1: periodo de retirada aleatorizada Evaluar la eficacia de remibrutinib, en los participantes con UCE y un UAS7 (Weekly Urticaria Activity Score) <16 en la semana 52 del estudio principal anterior teniendo en cuenta el tiempo hasta que se produzca uno de estos tres acontecimientos:recaída, discontinuación del tratamiento del estudio debido a la falta de eficacia o ingesta de medicación prohibida que cause gran confusión hasta la semana 24 en comparacion con placebo |
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E.2.2 | Secondary objectives of the trial |
To assess the long-term safety and tolerability of remibrutinib |
Evaluar la seguridad y la tolerabilidad a largo plazo de remibrutinib |
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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). |
El estudio incluye componentes de investigación de los biomarcadores opcionales adicionales. Las muestras se conservarán y se analizarán según los resultados de otras evaluaciones de biomarcadores realizadas en este estudio, el resultado global del estudio o de otros estudios. Se recogerán muestras de suero para la evaluación de los autoanticuerpos y de los biomarcadores exploratorios adicionales, p. ej., FcR1 soluble. Estas muestras de suero podrían utilizarse para comprender mejor la heterogeneidad de la enfermedad e identificar los marcadores de eficacia o de estratificación. Asimismo, se puede evaluar el efecto de la exposición a remibrutinib en los títulos de anticuerpos. Se incluirán descripciones detalladas de las pruebas en los informes de datos bioanalíticos. Los biomarcadores también podrían incluir análisis individuales o multiplexados dirigidos de biomarcadores (autoanticuerpos, proteínas, péptidos o metabolitos) o plataformas que no requieren establecer hipótesis (autoanticuerpos, proteínas, péptidos o metabolitos). |
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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. |
- El consentimiento informado por escrito se debe obtener antes de realizar cualquier evaluación. - Participantes adultos de ambos sexos >/= 18 años de edad. - Participantes que hayan completado de manera satisfactoria los estudios principales anteriores CLOU064A2301, CLOU064A2302, CLOU064A1301, CLOU064A2304 o CLOU064A2305 según los protocolos correspondientes. - Estar dispuesto a cumplir el protocolo del estudio y el calendario de visitas y ser capaz de hacerlo. |
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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. |
- Otras enfermedades con síntomas de urticaria o angioedema, que incluyen entre otras vasculitis urticarial, urticaria pigmentosa, eritema multiforme, mastocitosis, angioedema hereditario o urticaria inducida por fármacos. - Cualquier otra enfermedad cutánea asociada a picor crónico que pueda influir según el criterio del investigador en las evaluaciones y los resultados del estudio; p. ej., dermatitis atópica, penfigoide bulloso, dermatitis herpetiforme, prurito senil o psoriasis. - Signos de enfermedad cardiovascular de interés clínico (como, entre otros, infarto de miocardio, enfermedad isquémica cardíaca inestable, insuficiencia ventricular izquierda de clase III/IV de la NYHA [New York Heart Association], arritmia e hipertensión no controlada en los 12 meses anteriores al reclutamiento), trastornos neurológicos, psiquiátricos, pulmonares, renales, hepáticos, endocrinos, metabólicos y hematológicos, enfermedad gastrointestinal o inmunodeficiencia que, a juicio del investigador, pondría en riesgo la seguridad del participante, interferiría en la interpretación de los resultados del estudio o impediría la participación o el cumplimiento del protocolo por parte del participante. - Riesgo significativo de sangrado o trastornos de coagulación. - Antecedentes de sangrado gastrointestinalde interés clínico, p. ej., aquel que esté asociado al uso de fármacos antiinflamatorios no esteroideos (AINE). - Requisito de medicación antiplaquetaria, excepto el ácido acetilsalicílico hasta 100 mg/d o clopidogrel hasta 75 mg/d. El uso de tratamiento antiplaquetario dual (p. ej., ácido acetilsalicílico + clopidogrel) está prohibido. - Necesidad de recibir medicación anticoagulante (por ejemplo, warfarina o nuevos anticoagulantes orales [NACO]). - Antecedentes de enfermedad hepática o tratamiento actual para ello, incluida entre otras, hepatitis aguda o crónica, cirrosis o insuficiencia hepática o niveles de aspartato aminotransferasa (AST)/alanina aminotransferasa (ALT) superiores a 1,5 x el límite superior de normalidad (LSN) o índice internacional normalizado (INR) superior a 1,5 en las 2 últimas visitas disponibles del estudio principal anterior.
Pueden aplicarse otros criterios de exclusión definidos por el protocolo. |
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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 |
Tiempo hasta el primer acontecimiento compuesto (es decir, recaída [UAS7 >/=16], discontinuación del tratamiento del estudio debido a la falta de eficacia o ingesta de medicación prohibida que cause una gran confusión) durante el periodo de retirada aleatorizada |
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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 |
La aparición de acontecimientos adversos con el tratamiento (graves y no graves) durante el estudio de extensión. |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
End of Study |
Final del estudio |
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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 |
Tolerability |
Tolerabilidad |
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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 |
Estudio de extensión abierto, controlado con placebo con retirada aleatorizada (único brazo) |
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 | 8 |
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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LVLS |
Última visita del último paciente (LPLV) |
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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 | |
E.8.9.1 | In the Member State concerned days | 9 |
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 |