E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Hereditary Periodic Fevers (TRAPS, HIDS, or crFMF) |
Fiebres periódicas hereditarias (TRAPS, HIDS o FMFrc) |
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E.1.1.1 | Medical condition in easily understood language |
Hereditary Periodic Fevers |
Fiebres periódicas hereditarias |
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E.1.1.2 | Therapeutic area | Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10067783 |
E.1.2 | Term | Tumor necrosis factor receptor-associated periodic syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10016207 |
E.1.2 | Term | Familial mediterranean fever |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10072010 |
E.1.2 | Term | Hyper IgD syndrome |
E.1.2 | System Organ Class | 10010331 - Congenital, familial and genetic 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 randomized treatment epoch and for the overall study is to demonstrate that subcutaneous canakinumab administered every 4 weeks is superior to placebo in achieving a clinically meaningful reduction of disease activity defined as resolution of the index flare at Day 15 and no new disease flares over 16 weeks of treatment. |
El objetivo principal de la fase de tratamiento aleatorizado y del estudio global es demostrar que canakinumab subcutáneo administrado cada 4 semanas es superior a placebo en la consecución de una reducción clínicamente significativa de la actividad de la enfermedad definida como la remisión del número de brotes el día 15 y ningún nuevo brote de la enfermedad a lo largo de 16 semanas de tratamiento. |
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E.2.2 | Secondary objectives of the trial |
? To evaluate the percentage of patients who achieve a Physician Global Assessment of Disease Activity (PGA) <2 (?minimal? or ?none?) at Week 16 ? To evaluate the percentage of patients with the serologic remission at Week 16 (defined as C-reactive protein [CRP] <10 mg/L) ? To evaluate the percentage of patients with normalized Serum Amyloid A (SAA) level at Week 16 (defined as SAA <10 mg/L) ? To evaluate the percentage of canakinumab responders in Epoch 2 who maintain a clinically meaningful response (absence of new flares) when switched to canakinumab every 8 weeks compared to placebo (Epoch 3) ? To evaluate the long-term safety and tolerability and immunogenicity of canakinumab ? To evaluate the pharmacokinetics/ pharmacodynamics of canakinumab |
? Evaluar el porcentaje de pacientes que alcancen una evaluación global de la actividad de la enfermedad por parte del médico (PGA) <2 (?mínima? o ?ninguna?) en la semana 16. ? Evaluar el porcentaje de pacientes con remisión serológica en la semana 16 (definida como proteína C reactiva [PCR] <10 mg/l). ? Evaluar el porcentaje de pacientes con nivel normalizado de amiloide A sérico (AAS) en la semana 16 (definida como AAS <10 mg/l). ? Evaluar el porcentaje de respondedores a canakinumab en la fase 2 que mantengan una respuesta clínicamente significativa (ausencia de nuevos brotes) cuando cambien a canakinumab cada 8 semanas en comparación con placebo (fase 3) ? Evaluar la seguridad, tolerabilidad e inmunogenicidad a largo plazo de canakinumab ? Evaluar la farmacocinética/farmacodinámica de canakinumab. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patient's written informed consent (or parent's written informed consent in case of pediatric patient) at screening - Male and female patients at least 2 years of age at the time of the screening visit. - Confirmed diagnosis and active flare at randomization - CRP >10mg/L at randomization |
? Consentimiento informado escrito del paciente (o consentimiento informado escrito de los padres en caso de pacientes pediátricos) en la selección. ? Pacientes de ambos sexos de al menos 2 años de edad en el momento de la visita de selección. ? Diagnóstico confirmado de TRAPS, HIDS o FMFrc en la selección. ? Brote activo de TRAPS, HIDS o FMFrc en la randomizacion. ? PCR >10mg/l (rango normal de PCR ?10 mg/l) en la aleatorización. |
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E.4 | Principal exclusion criteria |
Use of the following therapies (within varying protocol defined timeframes): Corticosteroids, anakinra, canakinumab, rilonacept, tocilizumab, TNF inhibitors, abatacept, tofacitinib, rituximab, leflunomide, thalidomide, cyclosporine, intravenous immunoglobulin, 6-Merceptopurine, azathioprine, cyclophosphamide, or chlorambucil, any other investigational biologics - History of malignancy of any organ system (other than localized basal cell carcinoma of the skin or in - situ cervical cancer), treated or untreated - Significant medical diseases, including but not limited to the following: a. History of organ transplantation b. Elevated liver enzymes ?2x ULN d. Increase in total bilirubin e. Serious hepatic disorder (Child-Pugh scores B or C) f. Chronic Kidney Disease g. Thyroid disease h. Diagnosis of active peptic ulcer disease i. Coagulopathy j. Significant CNS effects including vertigo and dizziness - Any conditions or significant medical problems which immunecompromise the patient and/or places the patient at unacceptable risk for immunomodulatory therapy - Live vaccinations within 3 months prior to the start of the trial, during the trial, and up to 3 months following the last dose |
? Uso de los siguientes tratamientos (dentro de los distintos plazos definidos en el protocolo): Corticosteroides (prednisona oral) > 0,2 mg/kg/día (o superior al máximo de 15 mg/ día en niños con un peso superior a 60 kg), anakinra, canakinumab, rilonacept, tocilizumab, inhibidores de TNF, abatacept, tofacitinib, rituximab, leflunomida, talidomida, ciclosporina, inmunoglobulina intravenosa, 6-merceptopurina, azatioprina, ciclofosfamida o clorambucilo, inyecciones intraarticulares, periarticulares o intramusculares de corticosteroides, cualquier otro producto biológico en investigación. ? Antecedentes de tumores malignos de cualquier sistema orgánico (salvo carcinoma cutáneo de células basales localizado o cáncer de cuello uterino in situ) tratados o no tratados. ? Enfermedades médicas significativas, incluyendo entre otras: a. Antecedentes de trasplante de órganos. b. Nivel elevado de alanina aminotransferasa (ALT) ? 2x LSN. c. Nivel elevado de aspartato aminotransferasa (AST) ?2x LSN. d. Aumento de la bilirrubina total definido según los criterios comunes de terminología (CTC) de grado ?2. e. Trastorno hepático grave (puntuaciones B o C de Child-Pugh). f. Enfermedad renal crónica según los estadios de NKF ?4. g. Enfermedad tiroidea. h. Diagnóstico de enfermedad de úlcera péptica activa. i. Coagulopatía. j. Efectos significativos en el SNC incluidos vértigo y mareos. ? Cualquier condición o problema médico significativo que inmunocomprometa al paciente y/o le ponga en una situación de riesgo inaceptable para el tratamiento inmunomodulador, p. ej., a. Disminución del recuento absoluto de neutrófilos según grado ?1 de los CTC. b. Trombocitopenia de grado 1 de los CTC. c. Cualquier infección bacteriana, fúngica (salvo onicomicosis) o vírica activa o recurrente. d. Infección del VIH, infecciones de hepatitis B o hepatitis C. e. Presencia de tuberculosis f. Requisito de administración de antibióticos contra la TB latente. g. Signos clínicos o antecedentes de esclerosis múltiple u otras enfermedades desmielinizantes o síndrome de Felty. ? Administración de vacunas vivas durante los 3 meses anteriores al inicio del ensayo, durante el ensayo y hasta los 3 meses posteriores a la última dosis. |
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E.5 End points |
E.5.1 | Primary end point(s) |
Proportion of participants with resolution of initial flare at time of the randomization and absence of new flares. To demonstrate significant reduction of disease activity with canakinumab versus placebo |
Proporción de pacientes con resolucion del brote incial en el momento de la randomizacion y ausencia de nuevos brotes. Demostrar la reduccion significativa de la actividad de la enfermedad con canakinumab comparado con placebo |
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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) |
Percentage of participants who achieve Physician's global assessment < 2 Percentage of participants with the serologic remission |
Porcentaje de pacientes que consigan una Evaluación global de la actividad de la enfermedad por parte del médico < 2 Porcentaje de pacientes con remision serologica |
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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 | No |
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 | 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) | 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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 3 |
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 | 7 |
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 |
Belgium |
Canada |
Denmark |
France |
Greece |
Ireland |
Italy |
Japan |
Netherlands |
Finland |
Germany |
Hungary |
Spain |
Israel |
Russian Federation |
Switzerland |
Turkey |
United Kingdom |
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
|
LVLS |
ultima visita del ultimo paciente |
|
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 | 7 |
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 |