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 |
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 |
The primary objective of the study is to demonstrate that ligelizumab is superior to placebo and superior to omalizumab 300 mg q4w in change from baseline in UAS7 at Week 12 |
El objetivo principal del estudio es demostrar que ligelizumab (72 mg C4S y/o 120 mg C4S) es superior a placebo y superior a omalizumab 300 mg C4S en el cambio en el UAS7 en la semana 12 respecto a la basal. |
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E.2.2 | Secondary objectives of the trial |
To demonstrate that a greater proportion of subjects achieve UAS7=0 at Week 12 who are treated with ligelizumab 72 mg q4w and/or 120 mg q4w compared to placebo-treated subjects and compared with omalizumab 300 mg q4w treated subjects
To demonstrate the superiority of ligelizumab 72 mg q4w and/or 120 mg q4w treated subjects with respect to a reduction from baseline in the weekly itch severity score at Week 12 compared to placebo-treated subjects and omalizumab 300 mg q4w treated subjects
To demonstrate that a greater proportion of subjects who are treated with ligelizumab q4w achieve DLQI= 0-1 at Week 12 compared to placebo-treated subjects and omalizumab 300 mg q4w treated subjects
To demonstrate that the ligelizumab 72 mg q4w and/or 120 mg q4w treated subjects have a longer angioedema occurrence-free period compared with placebo-treated subjects and omalizumab 300 mg q4w treated subjects.
To demonstrate the safety and tolerability of ligelizumab 72 mg q4w and 120 mg q4w |
Demostrar que: Una proporción mayor de pacientes tratados con ligelizumab 72 mg C4S y/o 120 mg C4S consiguen UAS7 = 0 en S12 vs pacientes tratados con placebo y vspacientes que son tratados con omalizumab 300 mg C4S. La superioridad de pacientes tratados con ligelizumab 72 mg C4S y/o 120 mg C4S en relación a la reducción respecto a la basal en la puntuación semanal de la intensidad del picor en la S12 vs pacientes tratados con placebo y pacientes tratados con omalizumab 300 mg C4S. Una proporción mayor de pacientes tratados con ligelizumab 72 mg C4S y/o 120 mg C4S consiguen una UAS7 = 0 en S12 vs pacientes que son tratados con placebo y con pacientes que son tratados con omalizumab 300 mg C4S. Pacientes tratados con ligelizumab 72 mg C4S y/o 120 mg C4S registran un periodo más largo sin aparición de angioedema en comparación con los pacientes tratados con placebo y pacientes tratados con omalizumab 300 mg C4S. La seguridad y tolerabilidad de ligelizumab 72 mg C4S y 120 mg C4S. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Signed informed consent must be obtained prior to participation in the study. The subject’s, parent’s or legal guardian’s signed written informed consent and child’s assent, if appropriate, must be obtained before any assessment is performed. ● Male and female subjects ≥ 12 years of age at the time of screening. ● CSU diagnosis for ≥ 6 months. ● Diagnosis of CSU refractory to H1-AH at approved doses at the time of randomization, as defined by all of the following: ● The presence of itch and hives for ≥ 6 consecutive weeks at any time prior to Visit 1 (Day - 28 to Day -14) despite current use of non-sedating H1-antihistamine ● UAS7 score (range 0-42) ≥ 16 and HSS7 (range 0-21) ≥ 8 during the 7 days prior to randomization (Visit 110, Day 1) ● Subjects must be on H1-antihistamine at only approved doses for treatment of CSU starting at Visit 1 (Day -28 to Day -14) ● Willing and able to complete a daily symptom eDiary for the duration of the study and adhere to the study visit schedules. ● Other protocol-defined inclusion criteria may apply |
- Se deberá obtener el consentimiento informado firmado antes de la participación en el estudio. Se deberá obtener la firma del consentimiento informado por parte del sujeto, sus progenitores o su tutor legal y el asentimiento del niño, si procede, antes de realizar cualquier evaluación. - Hombres o mujeres de ≥ 12 años de edad en el momento de la selección. - Diagnóstico de UCE ≥ 6 meses. - Diagnóstico de UCE refractaria a dosis autorizadas de antihistamínicos H1 en el momento de la aleatorización, definido por las siguientes características: o Presencia de picor y habones durante ≥ 6 semanas consecutivas en cualquier momento previo a la visita 1 (del día -28 al día -14) a pesar del uso actual de antihistamínicos H1 no-sedantes. Puntuación de UAS7 (rango 0-42) ≥ 16 y HSS7 (rango 0-21) ≥ 8 durante los 7 días previos a la aleatorización (visita 110, día 1). - Los pacientes deben estar en tratamiento con dosis autorizadas de antihistamínicos H1 para la UCE a partir de la visita 1 (del día -28 al día -14). - Voluntad y capacidad para lcumplimentar un diario electrónico con los síntomas experimentados a diario durante todo el estudio y seguir el calendario de visitas. - Aplica Cualquier otro criterio de inclusión definido en el protocolo. |
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E.4 | Principal exclusion criteria |
History of hypersensitivity to any of the study drugs or their excipients or to drugs of similar chemical classes (i.e. to murine, chimeric or human antibodies). ● Subjects having a clearly defined cause of their chronic urticaria, other than CSU. This includes, but is not limited to, the following: symptomatic dermographism (urticaria factitia), cold-, heat-, solar-, pressure-, delayed pressure-, aquagenic-, cholinergicor contact-urticaria. ● Diseases, other than chronic urticaria, with urticarial or angioedema symptoms such as urticarial vasculitis, erythema multiforme, cutaneous mastocytosis (urticaria pigmentosa) and hereditary or acquired angioedema (eg, due to C1 inhibitor deficiency). ● Subjects with evidence of helminthic parasitic infection as evidenced by stools being positive for a pathogenic organism according to local guidelines. All subjects will be screened at Visit 1. If stool testing is positive for pathogenic organism, the subject will not be randomized and will not be allowed to rescreen. ● Any other skin disease associated with chronic itching that might influence in the investigators opinion the study evaluations and results (e.g. atopic dermatitis, bullous pemphigoid, dermatitis herpetiformis, senile pruritus, etc.). ● Prior exposure to ligelizumab or omalizumab. ● Any H2 antihistamine, LTRA (montelukast or zafirlukast) or H1 antihistamines use at greater than approved doses after Visit 1. ● Other protocol-defined exclusion criteria may apply |
- Antecedentes de hipersensibilidad a cualquiera de los fármacos del estudio o a sus excipientes, o a fármacos de clases químicas similares (es decir, anticuerpos murinos, quiméricos o humanos). - Pacientes que tienen una causa claramente definida de su urticaria crónica, diferente a la UCE. Esto incluye, pero no se limita a las siguientes: dermografismo sintomático (urticaria facticia), urticaria por el frío, por el calor, solar, por presión, por presión retardada, acuagénica, colinérgica o de contacto. - Enfermedades diferentes a la urticaria crónica con síntomas de urticaria o angioedema como vasculitis urticarial, eritema multiforme, mastocitosis cutánea (urticaria pigmentosa) y angioedema hereditario o adquirido (p. ej., debido a una deficiencia del inhibidor C1). - Pacientes con una infección parasitaria helmíntica evidenciada por un resultado positivo de un organismo patógeno presente en las heces, según las directrices locales. Se realizará la selección de todos los pacientes en la visita 1. Si la prueba de heces que identifica el organismo patógeno es positiva, el sujeto no se aleatorizará y no podrá volver a ser seleccionado. - Cualquier otra enfermedad cutánea asociada a picor crónico que pueda influir las opiniones de los investigadores, las evaluaciones y los resultados del estudio (p. ej., dermatitis atópica, penfigoide bulloso, dermatitis herpetiforme, prurito senil, etc.), - Exposición previa a ligelizumab o a omalizumab. - Cualquier antihistamínico H2, antagonistas de los receptores de leucotrienos (montelukast o zafirlukast) o antihistamínicos H1 utilizados en dosis superiores a las autorizadas tras la visita 1. - Aplica Cualquier otro criterio de exclusion definido en el protocolo. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Absolute change from baseline in UAS7 at Week 12 |
Cambio respecto a basal en la UAS7 en la semana 12. |
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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) |
● Complete absence of hives and itch at Week 12, assessed as percentage of subjects achieving UAS7 = 0 ● Improvement of severity of itch, assessed as absolute change from baseline in ISS7 score at Week 12 ● No impact on subjects quality of life at Week 12, assessed as % of subjects achieving DLQI = 0-1 ● Cumulative number of weeks that subjects achieve AAS7 = 0 responses between baseline and Week 12 ● Occurrence of treatment emergent adverse events during the study ● Occurrence of treatment emergent serious adverse events during the study |
- Ausencia completa de habones y picor en semana 12 evaluada como el porcentaje de pacientes que alcanzan un UAS7=0 - Mejora de la severidad del picor evaluada como el cambio absoluto en la puntuación ISS/ desde visita basal a semana 12 - Sin impacto en la calidad de vida de los pacientes en la semana 12, evaluado como el porcentaje de pacientes que alcancen DLQI = 0-1 - Número acumulado de semanas en las que los pacientes alcanzan respuestas AAS7 = 0 entre la basal y la semana 12. - Aparición de acontecimientos adversos causados por el tratamiento durante el estudio. - Aparición de acontecimientos adversos graves causados por el tratamiento durante el estudio |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
12 weeks and at each protocol defined study visit |
12 semanas en cada visita definida por protocolo. |
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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 To evaluate the use of rescue medication |
Calidad de vida Evaluar el uso de medicación de rescate |
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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) | Yes |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 4 |
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 | 10 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 73 |
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 |
Austria |
Brazil |
Bulgaria |
Canada |
Colombia |
Czech Republic |
Denmark |
France |
Germany |
Greece |
Guatemala |
Hungary |
India |
Korea, Republic of |
Malaysia |
Morocco |
Oman |
Peru |
Poland |
Russian Federation |
Singapore |
South Africa |
Spain |
Sweden |
Thailand |
Turkey |
United States |
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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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Completion of the study will be considered when all patients will have completed 52 weeks of treatment epoch and the full follow up epoch or have prematurely withdrawn from the study |
Se considerará la finalización del estudio cuando todos los pacientes han completado las 52 semanas de las fases de tratamiento y de eguimiento o se han discontinuado prematuramente del ensayo. |
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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 | 2 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial months | 7 |
E.8.9.2 | In all countries concerned by the trial days | 20 |