E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Moderate to Severe Atopic Dermatitis. |
Dermatitis atópica de moderada a grave |
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E.1.1.1 | Medical condition in easily understood language |
Atopic dermatitis is a chronic condition characterized by red, itchy, dry, bumpy patches of skin. Lesions are typically found in the hands, neck, upper chest, inner elbows, and backs of the knees. |
DA: enfermedad crónica con zonas de piel enrojecida,con picor,descamación,hinchazón. Las lesiones aparecen en manos,cuello, parte superior del pecho,cara interna de codos,parte posterior de rodillas |
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E.1.1.2 | Therapeutic area | Diseases [C] - Immune System Diseases [C20] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 21.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003639 |
E.1.2 | Term | Atopic dermatitis |
E.1.2 | System Organ Class | 100000004858 |
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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 |
- To evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in patients with moderate-to-severe Atopic Dermatitis. |
- Evaluar la eficacia de BMS-986166 y de branebrutinib, cada uno frente a placebo, en la semana 16 en participantes con DA moderada a grave. |
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E.2.2 | Secondary objectives of the trial |
- To further evaluate the efficacy of BMS-986166 and of branebrutinib, each versus placebo at Week 16 in patients with moderate-to-severe Atopic Dermatitis. - To assess the safety and tolerability of BMS-986166 and of branebrutinib in patients with moderate-to-severe Atopic Dermatitis. |
- Evaluar adicionalmente la eficacia de BMS-986166 y de branebrutinib, cada uno frente a placebo, en la semana 16 en participantes con DA moderada a grave. - Evaluar la seguridad y tolerabilidad de BMS-986166 y de branebrutinib en participantes con DA moderada a grave. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
•Females or males 18 (or local age of majority)-65 years inclusive •Dx of AD of at least 24 months duration •Screening EASI ≥ 12 and ≥ 16 at baseline •vIGA ≥ 3 at screening and baseline •documented history of inadequate control of AD by a stable regimen (≥ 4 weeks) of topical corticosteroids, calcineurin inhibitors or biologics, within 6 months of randomization or inappropriateness of tx dur to side effects or safety risks. •Documentation of positive VZV Ig antibody status or complete VZV vaccination within 90 days of first dosing. |
- Hombres o mujeres de 18 años (o mayoría de edad local) a 65 años inclusive -Dx de DA de al menos 24 meses de duración. -Screening EASI ≥ 12 y ≥ 16 en el momento basal -vIGA ≥ 3 en el screening y en el momento basal -Historia documentada de control inadecuado de la DA mediante un régimen estable (≥ 4 semanas) de corticosteroides tópicos, inhibidores de la calcineurina o biológicos, en los 6 meses anteriores a la aleatorización, o tx inapropiado debido a efectos secundarios o riesgos de seguridad. -Documentación de un estado positivo de anticuerpos Ig contra el VVZ (Virus Varicella Zoster) o una vacunación completa contra el VVZ en los 90 días siguientes a la primera dosis. |
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E.4 | Principal exclusion criteria |
•Any major illness, condition, infection, cancer or hx of cancer or lymphoproliferative disease, including prelymphoma •Pregnancy, lactation, or plans for either •Clinically relevant cardiovascular or pulmonary conditions (including severe sleep apnea) •History of significant ocular disease •History of diabetes mellitus Type 1 or uncontrolled diabetes mellitus Type 2 with hemoglobin ALC > 8% or diabetic patients with significant comorbidities like retinopathy or nephropathy • History of testicular disease or epididymal disease/disorder except uncomplicated epididymitis successfully treated with antibiotics •Serum creatinine and total bilirubin > 2mg/dL •eGFR < 60mL/min/1.73 m2 •ALT/AST > 1.5x ULN •Hemoglobin < 10 g/dL •Abnormal OCT test suggestive of macular or choroidal pathology
•Surgery within the past 30 days before first dose or planned surgery during the study •History of TB •Positive result for Hepatitis B, Hepatitis C, HIV infection •History of congenital or acquired immunodeficiency •Presence of COVID-19 symptoms, COVID (suspected or confirmed) within 12 weeks of screening, at screening, or on Day 1, known or suspected sequelae of any sort following a prior episode of COVID, COVID vaccination within 14 days of screening (or plans to receive COVID vaccine during the study) •High likelihood (based on subject history) of requiring rescue therapy in < 4 weeks of randomization •Evidence of acute AD flare between screening and baseline/randomization •Treatment with anticoagulant or antiplatelet therapies (including aspirin for cardioprotection within 2 weeks prior to randomization •AD-related prescription or OTC skin barrier treatments within 2 weeks of randomization •Use of strong or moderate inhibitors or inducers of CYP2C8 or 3A4 within 5 half-lives or 14 days prior to randomization (inhibitors) or within 3 weeks prior to randomization (inducers) •Use of systemic immunosuppressive drugs or oral herbal immunomodulatory medications within 8 weeks of randomization •IV immunoglobulin within 8 weeks of randomization or during the study •Use of biologics within 8 weeks to 6 months (depending on type) prior to randomization •Prior exposure to BTK inhibitors or S1PR modulators •Use of any immunomodulator or investigational drug within the longer of 5 PK half-lives or 5 PD half-lives or within 6 months prior to randomization •WBC < 3000/µL or > 14,000/µL •ANC < the lower of either LLN or 1500/µL •ALC < 1000/µL •Platelet count < 100,000/µL |
-Cualquier enfermedad grave, afección, infección, cáncer o antecedentes de cáncer o enfermedad linfoproliferativa, incluido el prelinfoma. -Embarazo, lactancia o planes de alguno de ellos. -Condiciones cardiovasculares o pulmonares clínicamente relevantes (incluyendo apnea del sueño grave) -Antecedentes de enfermedades oculares significativas -Historial de diabetes mellitus tipo 1 o diabetes mellitus tipo 2 no controlada con hemoglobina ALC > 8% o pacientes diabéticos con comorbilidades significativas como retinopatía o nefropatía - Antecedentes de enfermedad testicular o enfermedad/trastorno del epidídimo, excepto epididimitis no complicada tratada satisfactoriamente con antibióticos -Creatinina sérica y bilirrubina total > 2mg/dL -FGe < 60mL/min/1,73 m2 -ALT/AST > 1,5x ULN -Hemoglobina < 10 g/dL -Prueba OCT anormal sugestiva de patología macular o coroidea -Cirugía en los últimos 30 días antes de la primera dosis o cirugía prevista durante el estudio -Historial de tuberculosis -Resultado positivo para Hepatitis B, Hepatitis C, infección por VIH -Historia de inmunodeficiencia congénita o adquirida -Presencia de síntomas de COVID-19, COVID (sospechada o confirmada) en las 12 semanas anteriores al screening, en el momento del screening o en el día 1, secuelas conocidas o sospechadas de cualquier tipo tras un episodio anterior de COVID, vacunación contra COVID en los 14 días anteriores al screening (o planes para recibir la vacuna contra COVID durante el estudio) -Alta probabilidad (basada en el historial del sujeto) de requerir terapia de rescate en < 4 semanas desde la aleatorización -Evidencia de brote agudo de DA entre el screening y el momento basal /aleatorización -Tratamiento con anticoagulantes o antiagregantes plaquetarios (incluida la aspirina para cardioprotección) en las 2 semanas anteriores a la aleatorización. -Tratamientos de barrera cutánea con prescripción o sin prescripción relacionados con la DA en las 2 semanas anteriores a la aleatorización -Uso de inhibidores o inductores fuertes o moderados de CYP2C8 o 3A4 en un plazo de 5 semividas o 14 días antes de la aleatorización (inhibidores) o en un plazo de 3 semanas antes de la aleatorización (inductores) -Uso de fármacos inmunosupresores sistémicos o medicamentos inmunomoduladores orales a base de plantas en las 8 semanas anteriores a la aleatorización. -Inmunoglobulina intravenosa en las 8 semanas previas a la aleatorización o durante el estudio -Uso de fármacos biológicos entre 8 semanas y 6 meses (dependiendo del tipo) antes de la aleatorización -Exposición previa a inhibidores de BTK o moduladores de S1PR -Uso de cualquier inmunomodulador o fármaco en investigación en el plazo más largo a lo que suponen 5 vidas medias PK o 5 vidas medias PD, o en los 6 meses anteriores a la aleatorización -Recuento de glóbulos blancos < 3000/µl o > 14.000/µl -ANC < el menor de los dos valores de LLN o 1500/µL -ALC < 1000/µL -Recuento de plaquetas < 100.000/µl |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Mean percentage change from baseline in Eczema Area and Severity Index (EASI) score |
Media del cambio en el porcentaje en la puntuación EASI en la semana 16 respecto al momento basal |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1. At Week 16 |
1. En la semana 16 |
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E.5.2 | Secondary end point(s) |
2. Proportion of participants exhibiting a Validated Investigator Global Assessment for Atopic Dermatitis (vIGA-AD) score of 0 (cleared) or 1 (almost cleared) AND a ≥ 2 point reduction from baseline 3. Proportions of participants exhibiting a ≥ 50% (EASI-50) reduction from baseline in EASI score 4. Proportion of participants exhibiting a ≥ 4-point improvement from baseline in Pruritus NRS at Week 16. 5. Mean percentage change from baseline in Pruritus Numerical Rating Scale (NRS) score 6. Mean change from baseline in percentage of affected Body Surface Area (BSA) 7. Incidence and severity of all AE, and SAE 8. Incidence and severity of clinically significant changes in vital signs, ECG, OCT, PFT, and/or safety laboratory tests |
2. Proporción de participantes que presentan una puntuación de vIGA-AD de 0 (limpio) o 1 (casi limpio) Y una reducción de ≥ 2 puntos en la semana 16 respecto al momento basal 3. Proporción de participantes que presentan una reducción de ≥ 50% (EASI-50) en la puntuación EASI respecto al momento basal 4. Proporción de participantes que presentan una mejora de ≥ 4 puntos en la NRS del prurito en la semana 16 respecto al momento basal 5. Media del cambio en el porcentaje en la escala NRS del prurito respecto al momento basal 6. Media del cambio en el porcentaje de SAC afectada respecto al momento basal 7. Índice y gravedad de todos los AA y AAG 8. Incidencia y gravedad de los cambios clínicamente significativos en las constantes vitales, ECG, TCO, PFP y/0 pruebas de laboratorio de seguridad |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
2-8: At Week 16 |
2-8: En la semana 16 |
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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 | Yes |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
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) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
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 | 5 |
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 | 21 |
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 |
Australia |
Canada |
United States |
Austria |
Germany |
Poland |
Spain |
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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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End of study is defined as the last contact with the last participant (either last visit at which the last endpoint data is collected or last contact which could be a phone call). |
El final del estudio es definido como el último contacto con el último participante (ya sea la última visita en la que se recogen los últimos datos de las variables de evaluación o el último contacto que podría ser una llamada telefónica). |
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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 | 0 |
E.8.9.1 | In the Member State concerned months | 11 |
E.8.9.1 | In the Member State concerned days | 15 |
E.8.9.2 | In all countries concerned by the trial years | 1 |
E.8.9.2 | In all countries concerned by the trial months | 3 |
E.8.9.2 | In all countries concerned by the trial days | 15 |