E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin mediated amyloidosis (ATTR) |
Amiloidosis mediada por Transtiretina (ATTR) |
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E.1.1.1 | Medical condition in easily understood language |
ATTR is a hereditary disease caused by protein aggregates in the heart and the nervous system. It leads to heart dysfunction , damages to the nerves, and gastrointestinal and bladder dysfunctions. |
ATTR es una enfermedad hereditaria causada por agregados de prot. en el corazón y el sistema nervioso.Esto conduce a la disfunción del corazón, daño a los nervios,y disfunciones gastroint. y de vejiga |
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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 | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10007509 |
E.1.2 | Term | Cardiac amyloidosis |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 16.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10019889 |
E.1.2 | Term | Hereditary neuropathic amyloidosis |
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 | Yes |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
To evaluate the safety and tolerability of long-term dosing with ALN-TTR02. |
Evaluar la seguridad y tolerabilidad de la administración a largo plazo de ALN-TTR02 |
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E.2.2 | Secondary objectives of the trial |
To assess the PD effect associated with long-term dosing of ALN-TTR02 on serum TTR.
To assess changes from baseline in: ? Neurologic impairment, quality of life and disability, motor function impacting activities of daily living, and nutritional status. |
Evaluar el efecto FD asociado a la administración a largo plazo de ALN-TTR02 en las concentraciones séricas de TTR. Evaluar las variaciones desde el periodo basal en: *El deterioro neurológico, La calidad de vida y la escala de discapacidad, La función motora que influye en las actividades de la vida diaria, El estado nutricional . |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Previously received and tolerated ALN-TTR02 in Study ALN-TTR02-002. 2. Adequate Karnofsky performance status, liver function, and renal function.
Additional inclusion criteria are utilized to assess entry in PK subgroup and for the cardiac subgroup. |
1.Haber recibido y tolerado ALN-TTR02 anteriormente en el estudio ALN-TTR02-002. 2.Adecuado estado funcional de Karnofsky, Función hepática suficiente, Función renal Otros criterios de inclusión se utilizan para evaluar la entrada en el subgrupo PK (FC) y para el subgrupo cardiaco. |
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E.4 | Principal exclusion criteria |
1. Pregnant or nursing. 2. Has had a liver transplant. 3. Has a New York Heart Association heart failure classification >2. 4. Has unstable angina. 5. Has uncontrolled clinically significant cardiac arrhythmia. |
1.Embarazo o lactancia. 2.Haber recibido un trasplante de hígado. 3. Presentar una insuficiencia cardíaca de grado > 2 según la New York Heart Association. 4. Presentar angina de pecho inestable. 5. Presentar una arritmia cardíaca clínicamente significativa y no controlada. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To evaluate the safety and tolerability of long-term dosing with ALN-TTR02: ?assessment of adverse events (AEs), ?12 lead electrocardiograms (ECGs), ?vital signs (blood pressure, pulse rate, oral body temperature and respiratory rate), ?clinical laboratory safety tests (hematology, serum chemistry, thyroid function, coagulation, and urinalysis), ?ophthalmology examinations, and ?physical examinations. |
Las evaluaciones de la seguridad comprenderán el análisis de los acontecimientos adversos (AA), los ECG, las constantes vitales (presión arterial, frecuencia del pulso, temperatura corporal bucal y frecuencia respiratoria), análisis clínicos de seguridad (incluido hemograma, bioquímica en suero, parámetros de la función tiroidea, coagulograma y análisis de orina) y exploraciones físicas y oculares. |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The review of AEs will be done at each visit from Day 0 through through 56 days post last dose. The other assessments will be carried out at specific timepoints between screening and 56 days post last dose, as descibed in the study schedule. |
La revisión de los acontecimientos adversos se llevará a cabo en cada visita desde el día 0 hasta 56 días después de la última dosis. El resto de las evaluaciones se llevarán a cabo en puntos de tiempo específicos entre la detección y 56 días después de la última dosis, según lo expuesto en el programa de estudio .. |
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E.5.2 | Secondary end point(s) |
To assess the PD effect associated with long-term dosing of ALN-TTR02 on serum TTR.
To assess changes from baseline in: ? Neurologic impairment, quality of life and disability, motor function impacting activities of daily living, and nutritional status. |
Evaluar el efecto FD asociado a la administración a largo plazo de ALN-TTR02 en las concentraciones séricas de TTR. Evaluar las variaciones desde el periodo basal en: *El deterioro neurológico, La calidad de vida y la escala de discapacidad, La función motora que influye en las actividades de la vida diaria, El estado nutricional |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
An assessment of the concentrations of serum TTR, RBP, and Vitamin A will be determined at specified time points between screening and 56 days post last dose, as described in the study schedule.
Other assessments of neurologic impairment and QOL will be performed approximately every six months for approximately two years. |
Una evaluacion de las concentraciones séricas de TTR, PTR y la vitamina A seran determinadas en los momentos especificados entre el screening/momento basal y 56 dias después de la última dosis, como se describe en el calendario del estudio. Otras evaluaciones del deterioro neurologico y la calidad de vida seran realizadas aproximadamente cada 6 meses durante aproximadament 2 años. |
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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 | No |
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 | Yes |
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 | No |
E.8.1.1 | Randomised | No |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
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 | No |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 1 |
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 | 2 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 9 |
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 |
Brazil |
France |
Germany |
Portugal |
Spain |
Sweden |
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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LVLS |
Ultima visita del ultimo paciente. LVLS |
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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 | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |