E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Chronic Spontaneous Urticaria |
urticaria crónica espontánea |
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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 |
To characterize the dose-response relationship of LOU064 administered once or twice daily in subjects with CSU with respect to change from baseline in UAS7 at Week 4 |
El objetivo principal de este estudio es caracterizar la relación dosis-respuesta de LOU064, administrado una o dos veces al día, en pacientes con UCE, con respecto al cambio del UAS7 basal en la semana 4. |
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E.2.2 | Secondary objectives of the trial |
To evaluate: - the efficacy of LOU064 compared to placebo with respect to change from baseline in UAS7 at Week 12 - the efficacy of LOU064 compared to placebo with respect to change from baseline in UAS7 over time - the efficacy of LOU064 compared to placebo with respect to achievement of complete clinical response (UAS7= 0) over time - the efficacy of LOU064 compared to placebo with respect to achievement of disease control (UAS7≤ 6) over time - the effect of LOU064 on angioedema (AAS7) with respect to the number of weeks with an AAS7= 0 response from baseline through Week 12 - the effect of LOU064 on disease-related quality of life with respect to achievement of a DLQI score of 0 or 1 at Week 4 and Week 12 - the effect of LOU064 on CSU related quality of life with respect to change from baseline in DLQI at Week 4 and Week 12 - the pharmacokinetics of LOU064 resulting from oral dosing at Week 4 and Week 12 - safety and tolerability of LOU064 in subjects with CSU |
Evaluar la eficacia de LOU064 comparado con placebo, con respecto al cambio del UAS7 basal en la semana 12. Evaluar la eficacia de LOU064 comparado con placebo, con respecto al cambio del UAS7 basal a lo largo del tiempo. Evaluar la eficacia de LOU064 comparado con placebo, con respecto a la consecución de respuesta clínica completa (UAS7 = 0) a lo largo del tiempo. Evaluar la eficacia de LOU064 comparado con placebo, con respecto a la consecución de control de la enfermedad (UAS7 </= 6) a lo largo del tiempo. Evaluar el efecto de LOU064 en el angioedema (AAS7), con respecto al número de semanas con una respuesta AAS7 = 0, desde la visita basal hasta la semana 12. Evaluar el efecto de LOU064 en la calidad de vida relacionada con la enfermedad, con respecto a la consecución de una puntuación del DLQI de 0 o 1 en la semana 4 y en la semana 12. -la farmacocinética de LOU064 resultante de la dosificacion oral en semana 4 y 12 -seguridad y tolerabilidad de LOU064 en sujetos con UCE. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Signed informed consent must be obtained prior to participation in the study 2. Male and female subjects aged ≥18 years of age 3. CSU diagnosis for ≥ 6 months prior to screening 4. Diagnosis of CSU inadequately controlled by second generation H1-antihistamines at the time of randomization as defined in the following: - The presence of itch and hives for ≥6 consecutive weeks prior to screening in spite of use of non-sedating H1-antihistamines according to local treatment guidelines during this time period - UAS7 score (range 0-42) ≥16 and HSS7 score (range 0-21) ≥ 8 during 7 days prior to randomization (Day 1) 5. Willing and able to complete an Urticaria Participant Daily eDiary (UPDD) for the duration of the study
Other protocol-defined inclusion criteria may apply |
1. El consentimiento informado firmado deberá obtenerse antes de la participación en el estudio. 2. Pacientes adultos hombres y mujeres con edad >/=18 años. 3. Diagnóstico de UCE durante >/= 6 meses antes de la selección. 4. Diagnóstico de UCE inadecuadamente controlada con antihistamínicos H1 de segunda generación, definido por lo siguiente: -Presencia de picor y habones durante >/= 6 semanas consecutivas antes de la selección a pesar del uso de antihistamínicos H1 no sedantes según las pautas locales de tratamiento durante este periodo de tiempo. -Puntuación UAS7 (rango 0-42) >/=16 y puntuación HSS7 (rango 0-21) >/= 8 durante 7 días antes de la aleatorización (día 1). 5. Estar dispuesto y ser capaz de completar el diario del participante de urticaria (UPDD) durante el estudio.
Otros criterios de exclusion definidos en el protocolo pueden ser aplicados. |
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E.4 | Principal exclusion criteria |
1. Hypersensitivity to any of the study treatments 2. Clearly defined, predominant or sole trigger of their chronic urticaria (chronic inducible urticaria) 3. Other diseases with symptoms of urticaria or angioedema 4. Other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results 5. Known or suspected history of an ongoing, chronic or recurrent infectious disease including but not limited to opportunistic infections (eg tuberculosis, atypical mycobacterioses, listeriosis or aspergillosis), HIV, Hepatitis B/C. 6. Pregnant or nursing (lactating) women 7. Women of child-bearing potential not using highly effective methods of contraception
Other protocol-defined exclusion criteria may apply |
1. hipersensibilidad a cualquier tratamiento del estudio. 2. Pacientes con un desencadenante único o predominante, claramente definido de su urticaria crónica (urticaria crónica inducible) incluida urticaria facticia (demografismo sintomático), urticaria por frio, por calor, solar, por presión, retardada por presión, acuagénica, colinérgica o por contacto. 3. Otras enfermedades con síntomas de urticaria o angioedema, incluido pero no limitado a vasculitis urticarial, urticaria pigmentosa, eritema multiforme, mastocitosis, urticaria herediaria o urticaria inducida por fármacos/adquirida. 4. Cualquier otra enfermedad cutánea asociada picazón crónico que podría influir, a criterio del investigador, en las evaluaciones y resultados del estudio, por ejemplo, dermatitis atópica, penfigoide bulloso, dermatitis herpetiforme, prurito senil o psoriasis. 5. Antecedentes conocidos o sospechados de una enfermedad infecciosa recurrente o crónica, en curso, incluido pero no limitado a infecciones oportunistas (por ejemplo, tuberculosis, micobacteriosis atípica, listeriosis o aspergillosis), VIH, hepatitis B/C. 6. Mujeres embarazadas o lactantes. 7. Mujeres fértiles que no utilicen métodos contraceptivos altamente efectivos.
Otros criterios de exclusión pueden ser aplicados. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Change from baseline in weekly Urticaria Activity Score (UAS7) |
Cambio de Puntuación UAS7 basal semanal. |
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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) |
- Change from baseline in UAS7 at Week 12 - Change from baseline in UAS7 over time - Complete absence of hives and itch, assessed as UAS7= 0 response over time - Disease control (UAS7≤ 6) over time - Cumulative number of weeks with an AAS7= 0 response between baseline and Week 12 - DLQI score of 0 or 1 at Week 4 and 12 - Change from baseline in DLQI score at Week 4 and 12 - Concentrations of LOU064 in blood and calculation of respective PK parameters at Week 4 and Week 12 - Safety endpoints will include but not be limited to: - Occurrence of treatment emergent adverse events during the study - Occurrence of treatment emergent serious adverse events during the study |
Cambio de UAS7 basal a la semana 12 – Cambio de UAS7 de la visita basal a lo largo del tiempo – Ausencia completa de habones y picor, evaluado con una respuesta de UAS7 = 0 a lo largo del tiempo – Respuesta de UAS7 </= 6 a lo largo del tiempo – Número acumulado de semanas con una respuesta en la AAS7 = 0 entre la visita basal y la semana 12 – Puntuación del DLQI de 0 o 1 a la semana 4 y a la semana 12 – Cambio desde la visita basal en la puntuación del DLQI a la semana 4 y semana 12 – Concentraciones de LOU064 en sangre y cálculo de los parámetros PK respectivos a la semana 4 y a la semana 12 – Las variables de seguridad incluirán pero no estarán limitadas a: - Aparición de acontecimientos adversos que surjan durante el estudio – Aparición de acontecimientos adversos graves que surjan durante el estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
week 4 and week 12 |
semana 4 y semana 12 |
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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 | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | Yes |
E.6.13.1 | Other scope of the trial description |
Quality of Life |
Calidad de vida. |
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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) | 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 | 7 |
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 | 47 |
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 |
Belgium |
Canada |
Czech Republic |
Denmark |
France |
Germany |
Hungary |
Japan |
Netherlands |
Poland |
Slovakia |
Spain |
United Kingdom |
United States |
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E.8.7 | Trial has a data monitoring committee | No |
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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Study completion is defined as when the last subject finishes their Study Completion visit, and any repeat assessments associated with this visit have been documented and followed-up appropriately by the investigator, or in the event of an early study termination decision, the date of that decision. |
La finalización del estudio se define cuando el último sujeto finaliza su visita de finalización del estudio, y cualquier evaluación repetida asociada con esta visita ha sido documentada y seguida de manera apropiada por el investigador, o en el caso de una decisión de terminación anticipada del estudio, la fecha de esa decisión. |
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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 | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
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 | 6 |
E.8.9.2 | In all countries concerned by the trial days | 0 |