TAFAMIDIS for Transthyretin cardiac amyloidosis

Inclusion criteria

• {"criterion_text":"- Diphosphonate scintigraphy with 99mTc-labelled radiotracers (grade 2 or 3 uptake) and cardiac involvement confirmed by means of echocardiography, with an end-diastolic interventricular septal wall thickness exceeding 12 mm and no evidence of a monoclonal protein by negative serum free light chain and negative serum and urine immunofixation OR Extracardiac biopsy positive for ATTR amyloidosis and cardiac involvement confirmed by means of echocardiography, with an enddiastolic interventricular septal wall thickness exceeding 12 mm OR Cardiac biopsy positive for ATTR amyloidosis\n- Medical history of heart failure - NYHA I-III\n- Age > 18 years and < 90 at screening\n- Capable of providing written informed consent, willing and able to adhere to protocol requirements\n- Patients with or without renal failure will also be included (for those with stage 4/5 CKD no late gadolinium enhancement will be performed)\n- Able to comply with approved Summary of Product Characteristics recommendations for treatment with tafamidis 61mg"}

Exclusion criteria

• {"criterion_text":"- Confirmed diagnosis of light-chain amyloidosis\n- Familial amyloid polyneuropathy\n- NYHA IV\n- Heart failure due to other condition than CA in the opinion of the investigator\n- History of liver or cardiac transplant\n- Previous treatment with tafamidis or other alternatives in transthyretin amyloidosis\n- Severe malnutrition\n- Implanted cardiac device – pacemaker, defibrillator, cardiac resynchronization therapy\n- Devices or other material non-MRI conditional\n- Liver transaminases > 2 upper normal limit\n- Participating in another investigational study\n- Subjects requiring treatment with calcium channel blockers or digitalis\n- Subjects using non-steroidal anti-inflammatory drugs (NSAIDS), tauroursodeoxycholate and doxycycline\n- Investigator determines that the subject is not suitable for study participation for any other reason\n- Subjects who are pregnant females; breastfeeding females; males and females of childbearing potential who are unwilling or unable to use a highly effective method of contraception for the duration of the study and for at least 28 days, after last dose of tafamidis"}

Primary endpoints

• {"endpoint_text":"- Change from baseline at each point in CMR imaging parameters, including: ventricular volumes, mass, ejection fraction; native T1 and T2 mapping; ECV; LookLocker at 2, 5 and 10 minutes; LGE, Strain analysis and 4D flow","definition_or_measurement_approach":"Change from baseline assessed at each study timepoint using cardiac magnetic resonance (CMR) imaging parameters (ventricular volumes, mass, ejection fraction; native T1/T2 mapping; extracellular volume (ECV); Look-Locker at 2, 5 and 10 minutes; late gadolinium enhancement (LGE); strain analysis; 4D flow); evaluated before and after 12 months of tafamidis treatment."}

Secondary endpoints

• {"endpoint_text":"- Frequency of heart failure related hospitalization and all-cause mortality","definition_or_measurement_approach":"Counts/frequency of heart failure-related hospitalizations and all-cause mortality during study follow-up."}
• {"endpoint_text":"- Change from baseline at each point in the Kansas City Cardiomyopathy","definition_or_measurement_approach":"Change from baseline in Kansas City Cardiomyopathy Questionnaire score at each assessment timepoint."}
• {"endpoint_text":"- Questionnaire overall score","definition_or_measurement_approach":"Overall score from patient-reported questionnaire (as specified in study) compared to baseline."}
• {"endpoint_text":"- Change from baseline at each point in 6MWT distance","definition_or_measurement_approach":"Change from baseline in 6-minute walk test distance at each assessment timepoint."}
• {"endpoint_text":"- Change from baseline at each point in NT-proBNP concentration","definition_or_measurement_approach":"Change from baseline in NT-proBNP laboratory concentration at each assessment timepoint."}
• {"endpoint_text":"- Change from baseline at each point in NYHA classification","definition_or_measurement_approach":"Change from baseline in New York Heart Association (NYHA) functional classification at each assessment timepoint."}
• {"endpoint_text":"- Change from baseline at each point in echocardiographic parameters","definition_or_measurement_approach":"Change from baseline in echocardiographic measurements at each assessment timepoint."}

Portugal

Earliest CTIS Part Ii Submission Date

31-10-2024

Latest Decision Or Authorization Date

06-11-2024

Processing Time Days

6

Number Of Sites

2

Number Of Participants

30

Primary sponsor

Full Name

Unidade Local De Saude De Tras-Os-Montes E Alto Douro E.P.E.

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Portugal

Third parties

• {"country":"Portugal","full_name":"CCAB Centro Clinico Academico Braga Associacao","duties_or_roles":"sponsorDuties codes: 1, 11, 12, 13, 15 (Submission to the european authorities), 5, 6, 8","organisation_type":"Pharmaceutical company"}