E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Cardiac amyloidosis caused by transthyretin |
Amiloidosi cardiaca da transtiretina |
|
E.1.1.1 | Medical condition in easily understood language |
Cardiac amyloidosis caused by transthyretin |
Amiloidosi cardiaca causata da transtiretina |
|
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 | PT |
E.1.2 | Classification code | 10007509 |
E.1.2 | Term | Cardiac amyloidosis |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 efficacy (superiority) of Doxy/TUDCA in patients with cardiac ATTR amyloidosis, |
Valutare l'efficacia di Doxy/TUDCA nei pazienti con amiloidosi cardiaca da transtiretina. |
|
E.2.2 | Secondary objectives of the trial |
-To compare overall survival at 18 and 30 months of patients receiving Doxy/TUDCA in addition to standard supportive therapy with that of patients receiving standard supportive therapy alone. - To assess safety of Doxy/TUDCA by measuring the rate and grade of adverse events. - To assess changes in biochemical, echocardiographic, and clinical markers of disease severity during and after treatment. - To assess the impact of re-treatment with Doxy/TUDCA in patients who experience a major cardiac event after Doxy/TUDCA. - To assess discontinuation on biochemical, echocardiographic, and clinical markers of disease severity. - To assess the impact of treatment with Doxy/TUDCA in patients originally enrolled in the control arm who experience a “major cardiac event” and are then given Doxy/TUDCA on biochemical, echocardiographic, and clinical markers of disease severity. |
- confrontare la sopravvivenza globale a 18 e 30 mesi dei pazienti trattati Doxy/TUDCA in aggiunta alla terapia di supporto standard, rispetto ai pazienti trattati unicamente con terapia di supporto standard. - valutare la sicurezza di Doxy/TUDCA, misurando frequenza e grado degli eventi avversi. - valutare i cambiamenti negli esami biochimici, nell’esame ecocardiografico, e nei marcatori clinici di gravità della malattia, durante e dopo il trattamento. - valutare l'impatto del ri-trattamento con Doxy/TUDCA sugli esami biochimici, ecocardiografici e sui marker clinici di gravità della malattia nei pazienti che presentano un importante evento cardiaco dopo la sospensione di Doxy/TUDCA. - valutare l'impatto della discontinuazione sugli esami biochimici, ecocardiografici e sui marker clinici della malattia. - valutare l'impatto del trattamento con Doxy/TUDCA su marcatori biochimici, ecografici e clinici di gravità della malattia nei pazienti originariamente arruolati nel gruppo di contro |
|
E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
- Diagnosis of ATTRwt amyloidosis, or ATTRm p.Ile68Leu and p.Val122Ile; - 18 years or older; - cardiac involvement (mean left ventricular wall thickness >12 mm in the absence of other causes); - history of occurrence of at least 1 event of symptomatic heart failure; - stable diuretic dosage for at least 2 weeks before treatment initiation; - agree to practice effective methods of contraception where necessary - voluntary written consent |
- diagnosi di amiloidosi ATTRwt, o ATTRm p.Ile68Leu e p.Val122Ile. - età maggiore di 18 anni - coinvolgimento cardiaco (spessore della parete ventricolare media >12 mm assenza di altre cause) - storia di insorgenza di almeno un caso di insufficienza cardiaca sintomatica - dosaggio diuretico stabile per almeno due settimane prima di iniziare il trattamento - utilizzo di adeguato metodo contraccettivo, ove necessario - consenso informato scritto |
|
E.4 | Principal exclusion criteria |
- Non-ATTR amyloidosis - pregnant or nursing women - uncontrolled bacterial, viral, fungal, HIV, HBV, or HCV infection; - presence of other active malignancy with - known allergy to tetracycline; - treatment with drugs potentially affecting doxycycline absorption - significant acute gastrointestinal symptoms; - active peptic ulceration and/or esophageal reflux disease |
- amiloidosi non-ATTR - donne in gravidanza o in allattamento - infezione non controllata - presenza di altri tumori maligni attivi - allergia nota alle tetracicline - trattamento con farmaci che potenzialmente influenzano l'assorbimento della doxiciclina - sintomi gastrointestinali acuti significativi - ulcera peptica attiva e/o malattia da reflusso esofageo |
|
E.5 End points |
E.5.1 | Primary end point(s) |
Major cardiac events |
Eventi cardiaci maggiori |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
|
E.5.2 | Secondary end point(s) |
Overall survival; Adverse events equal or higher grade 3 (CTCAE v 5.0); Changes in BNP, NT-proBNP, cTnI, mLVW, EF, MCF, GLS, 6MWT |
Sopravvivenza globale; Eventi avversi grado 3 o superiore (CTCAE v 5.0); Cambiamenti nei valori di BNP, NT-proBNP, cTnI, spessore mLVW, EF, MCF, GLS, 6MWT |
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
18 and 30 months; At each visit; After 6, 12, 18 months during treatment and at 6, 12 months after the end of treatment |
18 e 30 mesi; Ad ogni visita; A 6, 12 e 18 mesi durante il trattamento, e 6 e 12 mesi dopo la sospensione del trattamento rispetto al basale |
|
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 | 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 | Yes |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Terapia di supporto standard |
Standard supportive therapy |
|
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 | 4 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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
|
|
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 | 0 |
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 | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |