E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin amyloid cardiomyopathy (ATTR CM) |
Miocardiopatía amiloidea por transtiretina (MC ATTR) |
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E.1.1.1 | Medical condition in easily understood language |
Heart disease due to TTR amyloidosis |
Amiloidosis cardíaca por TTR |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10002020 |
E.1.2 | Term | Amyloid cardiomyopathy |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To compare the effect of two dose levels of NNC6019-0001 (30 mg/kg and 100 mg/kg) versus placebo on: • change in 6-minute walk test and • change in NT-proBNP from baseline to week 52 in participants with hATTR or wtATTR cardiomyopathy. |
Comparar el efecto de dos niveles de dosis de NNC6019-0001 (30 mg/kg y 100 mg/kg) y de un placebo en: • variación en la prueba de marcha de 6 minutos y • variación del NT-proBNP entre el momento basal y la semana 52 en participantes con miocardiopatía ATTRh o ATTRn. |
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E.2.2 | Secondary objectives of the trial |
1) To compare the effect of two dose levels of NNC6019-0001 (30 mg/kg and 100 mg/kg) versus placebo on: • biomarkers • pharmacodynamic endpoints from baseline to week 52 in participants with hATTR or wtATTR cardiomyopathy. 2) To compare the effect of two dose levels of NNC6019-0001 (30 mg/kg and 100 mg/kg) versus placebo on: • safety and tolerability from baseline to week 64 in participants with hATTR or wtATTR cardiomyopathy. |
1) Comparar el efecto de dos niveles de dosis de NNC6019-0001 (30 mg/kg y 100 mg/kg) y de un placebo en: • biomarcadores • criterios de valoración farmacodinámicos entre el momento basal y la semana 52 en participantes con miocardiopatía ATTRh o ATTRn. 2) Comparar el efecto de dos niveles de dosis de NNC6019-0001 (30 mg/kg y 100 mg/kg) y de un placebo en: • seguridad y tolerabilidad. entre el momento basal y la semana 64 en participantes con miocardiopatía ATTRh o ATTRn. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Male or female. 2. Age greater than or equal to 18 to below 85 years at the time of signing informed consent. 3. Have an established diagnosis of ATTR CM with either wild-type TTR or hereditary TTR genotype as per local standards. 4. Expected to be on stable doses of cardiovascular medical therapy 6 weeks prior to the randomisation visit. 5, Known end-diastolic interventricular septal wall thickness greater than or equal to12 mm. 6. Presently classified as New York Heart Association (NYHA) Class II-III. 7. NT-proBNP concentration greater than or equal to 650 pg/mL in sinus cardiac rhythm and greater than1000 pg/mL in atrial fibrillation at screening. 8. Completed greater than or equal to 150 meters to equal to or below 450 meters on the 6-MWT at screening. 9. Estimated glomerular filtration rate (eGFR) greater than or equal to 25 mL/min/1.73 m^2 at screening. |
1. Varones o mujeres. 2. Mayor o igual de 18 años o menor de 85 años de edad en el momento de firmar el consentimiento informado. 3. Diagnóstico establecido de MC ATTR con genotipo de TTR natural o hereditario según las normas locales. 4. Previsión de recibir dosis estables de tratamiento médico cardiovascular 6 semanas antes de la visita de aleatorización. 5. Grosor conocido del tabique interventricular telediastólico igual o mayor de 12 mm. 6. Clase II-III de la New York Heart Association (NYHA) en la actualidad. 7. Concentración de NT-proBNP ≥ 650 pg/ml en ritmo cardíaco sinusal y > 1000 pg/ml en fibrilación auricular en la selección. 8. Mayor o igual a 150 metros y menor de 450 metros recorridos en la 6MWT en la selección. 9. Filtración glomerular estimada (FGe) igual o mayor de 25 ml/min/1,73 m2 en la selección. |
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E.4 | Principal exclusion criteria |
1. Cardiomyopathy not primarily caused by ATTR CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease 2. A prior solid organ transplant. 3. Planned solid organ transplant during the study. 4. Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, in-situ carcinomas of the cervix, or in-situ/high grade prostatic intraepithelial neoplasia (PIN) or low-grade prostate cancer) within 5 years before screening. 5. Current treatment with calcium channel blockers with conduction system effects (e.g., verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digoxin will only be allowed if required for management of atrial fibrillation with rapid ventricular response. 6. Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularization, cardiac valve repair, or major surgery within 3 months of screening. 7. Body weight greater than 120 kg (264.6 lb) at screening. 8. History of contrast allergy or adverse reactions to gadolinium-containing agents. |
1. Miocardiopatía no causada principalmente por MC ATTR, por ejemplo, miocardiopatía por hipertensión, cardiopatía valvular o cardiopatía isquémica 2. Trasplante previo de órgano sólido. 3. Trasplante de órgano sólido programado durante el estudio. 4. Presencia o antecedentes de neoplasia maligna (distinta de cáncer basocelular o espinocelular de la piel, carcinoma in situ del cuello uterino o neoplasia intraepitelial prostática (NIP) in situ o de alto grado o cáncer de próstata de bajo grado) en los 5 años previos a la selección. 5. Tratamiento actual con antagonistas del calcio con efectos en el sistema de conducción (p. ej., verapamilo, diltiazem). Se permite el uso de antagonistas del calcio dihidropiridínicos. Solo se permitirá el uso de digoxina en caso necesario para tratar la fibrilación auricular con respuesta ventricular rápida. 6. Síndrome coronario agudo, angina inestable, ictus, accidente isquémico transitorio (AIT), revascularización coronaria, reparación de válvula cardíaca o intervención de cirugía mayor en los 3 meses previos a la selección. 7. Peso corporal mayor de 120 kg en la selección. 8. Antecedentes de alergia al contraste o reacciones adversas a los fármacos que contienen gadolinio. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Change in 6-minute walk test (6-MWT) 2. Change in NT-proBNP |
1. Variación en la prueba de marcha de 6 minutos (6MWT) 2. Variación del NT-proBNP |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
1.-2.From baseline (week 0) to visit 15 (week 52) |
1.-2. Desde el momento basal (semana 0) hasta la visita 15 (semana 52) |
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E.5.2 | Secondary end point(s) |
1. Change in myocardial extracellular volume (ECV) 2. Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS) 3. Change in neuropathy impairment score (NIS) 4. Change in troponin I 5. Change in global longitudinal strain (GLS) on echocardiography 6. Number of treatment emergent adverse events 7. Time to occurrence of all-cause mortality 8. Number of CV events comprising hospitalisation due to CV events or urgent heart failure visits |
1.Variación del volumen extracelular del miocardio (VEC) 2. Variación de la Puntuación de resumen clínico (CSS) del Cuestionario de miocardiopatía de Kansas City (KCCQ) 3. Variación de la puntuación de deterioro por neuropatía (NIS) 4. Variación de la troponina I 5. Variación de la tensión longitudinal global (GLS) en la ecocardiografía 6. Número de acontecimientos adversos de aparición durante el tratamiento 7. Tiempo hasta la muerte por cualquier causa. 8. Número de episodios CV, que incluyen hospitalización por episodios CV o visitas urgentes por insuficiencia cardíaca |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
1.-5. From baseline (week 0) to visit 15 (week 52) 6.-8.From baseline (week 0) to visit 16 (week 64) |
1.-5. Desde el momento basal (semana 0) hasta la visita 15 (semana 52) 6.-8. Desde el momento basal (semana 0) hasta la visita 16 (semana 64) |
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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 | Yes |
E.6.13.1 | Other scope of the trial description |
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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 | Yes |
E.8.2.3.1 | Comparator description |
2 strengths of the same product |
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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
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 13 |
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 |
Canada |
Japan |
United States |
European Union |
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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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 | 10 |
E.8.9.1 | In the Member State concerned days | 23 |
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 | 10 |
E.8.9.2 | In all countries concerned by the trial days | 23 |