E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Transthyretin mediated amyloidosis (ATTR) |
amiloidosis mediada por la transtirretina (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 proteínas en el corazón y el SN. Esto conduce a la disfunción del corazón,los daños en los nervios, y disfunciones gastroint.y en la 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 determine the efficacy of ALN-TTR02 |
Determinar la eficacia de ALN-TTR02 |
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E.2.2 | Secondary objectives of the trial |
To determine the effect of ALN-TTR02 on various clinical parameters |
Determinar el efecto de ALN-TTR02 en varios parámetros clínicos |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
? Male or female of 18 to 80 years of age (inclusive); ? Have a diagnosis of FAP ? Meet Neuropathy Impairment Score requirements and Karnofsky performance status requirements ? Have adequate complete blood counts and liver function tests ? Have adequate cardiac function ? Have negative serology for hepatitis B virus (HBV) and hepatitis C virus (HCV) |
1.Cualquier sexo, de 18 a 80 años de edad (inclusive) 2.Presentar diagnóstico de PAF 3.alcanzar los requisitos de puntuación del deterioro Neuropático y los requisitos del estado de rendimiento de Karnofsky 4.Tener recuentos sanguíneos completos adecuados y pruebas de función hepática. 5.Tener la función cardíaca adecuada 6.Seronegativo para los virus de las hepatitis B (VHB) y C (VHC); |
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E.4 | Principal exclusion criteria |
? Had a prior liver transplant or is planned to undergo liver transplant during the study period; ? Has untreated hypo- or hyperthyroidism; ? Has known human immunodeficiency virus (HIV) infection; ? Had a malignancy within 2 years, except for basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix that has been successfully treated; ? Recently received an investigational agent or device ? Is currently taking diflunisal, tafamidis, doxycycline, or tauroursodeoxycholic acid |
Tener un trasplante de hígado previo o tener planeado someterse a trasplante de hígado durante el período de estudio; ? Tener hipo o hipertiroidismo no tratado ? Tener el virus de inmunodeficiencia humana (VIH); ? Tener un tumor maligno dentro de los ultimos 2 años, excepto para el carcinoma de células basales o escamosas de la piel o carcinoma in situ del cuello del útero que se ha tratado con éxito; ? Haya recibido recientemente un agente o dispositivo de investigación ? Esté tomando diflunisal, tafamidis, doxiciclina o ácido tauroursodeoxicólico |
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E.5 End points |
E.5.1 | Primary end point(s) |
The difference between the ALN TTR02 and placebo groups in the change from baseline of modified Neuropathy Impairment Score+7 (mNIS+7) |
la diferencia entre los grupos de ALN-TTR02 y placebo en cuanto a la variación de la puntuación NIS+7 modificada (mNIS+7) desde el momento basal |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
The difference between the ALN TTR02 and placebo groups in the change from baseline of modified NIS+7 (mNIS+7) at 18 months |
la diferencia entre los grupos de ALN-TTR02 y placebo en cuanto a la variación de la puntuación NIS+7 modificada (mNIS+7) hasta el mes 18. |
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E.5.2 | Secondary end point(s) |
The difference between ALN-TTR02 and placebo in the change from baseline in the following measurements: ? Quality of Life ? Modified Body Mass Index ? Autonomic function ? Muscle weakness as assessed by walking test |
la diferencia entre ALN-TTR02 y placebo en cuanto a la variación de las siguientes determinaciones desde el momento basal: . Calidad de vida . Indice de masa corporal modificado .Debilidad muscular evaluada por el test de caminata |
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
The difference between ALN-TTR02 and placebo in the change from baseline in the various clinical parameters at 18 months |
la diferencia entre ALN-TTR02 y placebo en cuanto a la variación de las siguientes determinaciones desde el momento basal hasta el mes 18: |
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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 | 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) | 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 | 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 | Yes |
E.8.2.3 | Other | No |
E.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 14 |
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 |
Brazil |
France |
Germany |
Italy |
Mexico |
Netherlands |
Portugal |
Spain |
Sweden |
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
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 2 |
E.8.9.1 | In the Member State concerned days | 0 |
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 | 2 |
E.8.9.2 | In all countries concerned by the trial days | 0 |