MAGNETICAL - MAGNetic resonance Evaluation of Tafamidis Impact in Cardiac AmyLoidosis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

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

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

13 Mar 2024 → ongoing

Decision date (initial)

2024-11-06

Transition trial

Yes

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

Funding sources

Laboratórios Pfizer Portugal · Sociedade Portuguesa de cardiologia/ Banco de Portugal

External identifiers

EU CT number

2024-518708-29-00

EudraCT number

2021-003158-21

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To evaluate the evolution and correlation of cardiac magnetic resonance imaging parameters before and after treatment with tafamidis for 12 months.

Secondary objectives 3

1. To identify clinical, analytical and imaging predictors of treatment response.
2. To assess the association of imaging markers evolution with mortality and heart failure related hospitalizations
3. To assess the association of imaging markers evolution with functional capacity and quality of life

Conditions and MedDRA coding

Transthyretin cardiac amyloidosis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. 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
2. Medical history of heart failure - NYHA I-III
3. Age > 18 years and < 90 at screening
4. Capable of providing written informed consent, willing and able to adhere to protocol requirements
5. Patients with or without renal failure will also be included (for those with stage 4/5 CKD no late gadolinium enhancement will be performed)
6. Able to comply with approved Summary of Product Characteristics recommendations for treatment with tafamidis 61mg

Exclusion criteria 15

1. Confirmed diagnosis of light-chain amyloidosis
2. Familial amyloid polyneuropathy
3. NYHA IV
4. Heart failure due to other condition than CA in the opinion of the investigator
5. History of liver or cardiac transplant
6. Previous treatment with tafamidis or other alternatives in transthyretin amyloidosis
7. Severe malnutrition
8. Implanted cardiac device – pacemaker, defibrillator, cardiac resynchronization therapy
9. Devices or other material non-MRI conditional
10. Liver transaminases > 2 upper normal limit
11. Participating in another investigational study
12. Subjects requiring treatment with calcium channel blockers or digitalis
13. Subjects using non-steroidal anti-inflammatory drugs (NSAIDS), tauroursodeoxycholate and doxycycline
14. Investigator determines that the subject is not suitable for study participation for any other reason
15. 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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

Secondary endpoints 7

1. Frequency of heart failure related hospitalization and all-cause mortality
2. Change from baseline at each point in the Kansas City Cardiomyopathy
3. Questionnaire overall score
4. Change from baseline at each point in 6MWT distance
5. Change from baseline at each point in NT-proBNP concentration
6. Change from baseline at each point in NYHA classification
7. Change from baseline at each point in echocardiographic parameters

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

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

Sponsor organisation

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

Address

Ulstmad, Avenida Da Noruega Avenida Da Noruega

City

Vila Real

Postcode

5000-508

Country

Portugal

Scientific contact point

Organisation

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

Contact name

COORDINATING INVESTIGATOR

Public contact point

Organisation

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

Contact name

COORDINATING INVESTIGATOR

Third parties 1

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 7 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications