Non-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

• Ages 18 to 130 years
• All sexes
• No healthy volunteers
• Adult, Older adult

Study population: Patients with a diagnosis of amyloid transthyretin (ATTR) amyloidosis

Trial locations and contacts

89 sites in 6 countries. Contact the study team or a site near you to ask about taking part.

About this study

Official title: A Non-interventional, Prospective, Multi-country Study Collecting Real-world Data on the Characteristics, Treatment Patterns, and Outcomes of Patients With Transthyretin (ATTR) Amyloidosis

Conditions

Transthyretin Amyloidosis, ATTR-CM, ATTRv-PN, ATTR, ATTR-Mixed, hATTR

Being tested

Treatment of transthyretin (ATTR) amyloidosis in observational study setting

Keywords

Amyloidosis, Transthyretin, Hereditary transthyretin-mediated (hATTR) amyloidosis, hATTR amyloidosis, Hereditary ATTR amyloidosis, Wild-type amyloidosis, wtATTR amyloidosis, ATTRv amyloidosis, ATTRwt amyloidosis, Polyneuropathy, Familial amyloid polyneuropathies, ATTR, Transthyretin amyloidosis, TTR-mediated amyloidosis, Polyneuropathies, Amyloid neuropathies, Amyloid neuropathies, familial, Amyloidosis, familial, Eplontersen, Non-interventional

Medical subject headings

Amyloidosis, Hereditary, Transthyretin-Related, Amyloidosis, Amyloid Neuropathies, Familial, Polyneuropathies, Amyloid Neuropathies, Amyloidosis, Familial

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

• Treatment of transthyretin (ATTR) amyloidosis in observational study settingDrug

  Data will be collected on patients with ATTR amyloidosis in a real-world setting

What is being measured

The primary outcome is the main question the study is designed to answer.

1. Demographic characteristics (overall and in patients initiating a treatment with eplontersen)

   • Age
   • Sex as determined by the investigator (male/female)
   • Race and ethnicity, where allowed

   Measured: From time of enrollment for up to 7 years

2. Treatment patterns (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following treatments will be assessed:

   • ATTR amyloidosis treatment: Tafamidis, Diflunisal, Acoramidis, Vutrisiran, Patisiran, Inotersen, Eplontersen, Doxycycline and taurodesoxycholic acid, Liver transplant
   • Heart failure/arrhythmia-related treatment: Diuretics, Angiotensin converting enzyme inhibitor, Angiotensin receptor blocker, Angiotensin receptor-neprilysin inhibitor, Anticoagulation, Beta-blockers, Sodium-glucose co-transporter-2 inhibitor, Mineralocorticoid receptor antagonist, Digoxin, Pacemaker use, Implantable cardioverter-defibrillator, Left ventricular assist device, Cardiac transplant, Transcatheter aortic valve replacement, Surgical aortic valve replacement
   • Polyneuropathy-related treatment: Antiepileptics (gabapentin, pregabalin, carbamazepine, phenytoin), Antidepressants, Topical pain treatments, Opioids, Tetrahydrocannabinol
   • Other: Medications for gastrointestinal symptoms, Vitamin A supplementation, Dialysis

   Measured: From time of enrollment for up to 7 years

3. Clinical characteristics (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following clinical characteristics will be assessed:

   • Modified body mass index (mBMI)
   • Medical history
   • TTR genetic test results
   • Family history of ATTR
   • Time period between the first symptoms to date of diagnosis of ATTR
   • Time since diagnosis of ATTR

   Measured: From time of enrollment for up to 7 years

4. Findings from biopsy (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following biopsy information will be collected:

   • Type of biopsy
   • Amyloid identification result (Positive, Negative, Inconclusive for amyloid)
   • Method of amyloid typing
   • Result of the biopsy (Normal/Abnormal)
   • Reason for considering the biopsy result abnormal

   Measured: From time of enrollment for up to 7 years

5. Findings from Cardiovascular magnetic resonance imaging (CMR) (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following information will be collected: extracellular volume (ECV), contrast use, left ventricular (LV) end-diastolic volume, LV end-systolic volume, LV ejection fraction, LV Mass Index, interventricular wall thickness, right ventricular Free Wall Thickness, LV Free Wall Thickness, left Atrial Volume Index, native T1 mapping, CMR result (Normal/Abnormal), reason for considering the result abnormal.

   Measured: From time of enrollment for up to 7 years

6. Findings from Bone tracer cardiac scintigraphy (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following information will be collected: Type of tracer, Heart to contralateral lung ratio (H/CL), Perugini grade, scintigraphy result (Normal/Abnormal), reason for considering the result abnormal.

   Measured: From time of enrollment for up to 7 years

7. Findings from Echocardiography (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following information will be collected: LV ejection fraction, LV End Diastolic Volume, LV End Systolic Volume LV End Diastolic Dimension, LV End Systolic Dimension, Interventricular Septal Thickness End Diastole, Posterial Wall Thickness End Diastole, Left Ventricular Mass Index, Left Atrial Volume, Left Atrial Volume Index, Mitral valve regurgitation, Aortic valve regurgitation, Tricuspid valve regurgitation, Pulmonic valve regurgitation, LV Outflow Gradient, Stroke Volume, Lateral early diastolic myocardial velocity (e' lateral), Medial early diastolic myocardial velocity (e' medial), Mitral E/e' Ratio, Early diastolic mitral inflow velocity (E), Late diastolic mitral inflow velocity (A), Mitral Peak E/A Ratio, Global LV longitudinal strain, Pulmonary artery systolic pressure, RV Free Wall Thickness Severity of Aortic stenosis, Severity of Mitral stenosis.

   Measured: From time of enrollment for up to 7 years

8. ECG variables (overall and in patients initiating a treatment with eplontersen)

   In order to address this objective, the following ECG information will be collected:

   • Interpretation of the ECG (Normal/Abnormal/Borderline)
   • Heart rhythm
   • Presence of extrasystoles
   • Presence of conduction abnormalities
   • Evidence of left ventricular hypertrophy (LVH)

   Measured: From time of enrollment for up to 7 years

9. Sural nerve and tibial nerve amplitude (overall and in patients initiating a treatment with eplontersen)

   Sural nerve and tibial nerve amplitude will be measured in overall and in patients initiating a treatment with eplontersen

   Measured: From time of enrollment for up to 7 years

10. Biomarker results (overall and in patients initiating a treatment with eplontersen)

    In order to address this objective, the following biomarker results will be collected:

    • Serum TTR levels
    • Complete blood count
    • Hemoglobin
    • Troponin I
    • Cystatin
    • Creatinine
    • Reported glomerular filtration rate (GFR)
    • Albumin
    • Liver enzymes: alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), total bilirubin
    • N-terminal pro B-type natriuretic peptide (NT-proBNP)
    • Vitamin A level
    • Neurofilament light chain (NfL)
    • International normalized ratio (INR) test

    Measured: From time of enrollment for up to 7 years

11. Urine test results (overall and in patients initiating a treatment with eplontersen)

    In order to address this objective, the following test results will be collected:

    • Urine albumin-creatinine ratio (UACR)
    • Urine protein creatinine ratio (UPCR)

    Measured: From time of enrollment for up to 7 years

12. Clinical manifestations (signs and symptoms) of ATTR amyloidosis (overall and in patients initiating a treatment with eplontersen)

    In order to address this objective, the following clinical manifestations will be assessed:

    ischemic heart disease, acute myocardial infarction, heart failure, atrial fibrillation, arrhythmias, conduction system disease, aortic valve stenosis polyneuropathy, carpal tunnel syndrome, autonomic neuropathy, nephrotic syndrome, subnephrotic proteinuria, gastrointestinal dysfunction, chronic kidney disease / acute kidney injury, spinal stenosis, spinal stenosis surgery, hepatomegaly, ascites, oedema, other amyloidosis related manifestations (e.g., Popeye's sign, tendon rupture)

    Measured: From time of enrollment for up to 7 years

13. 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary score (overall and in patients initiating a treatment with eplontersen)

    The SF-36v2 is a 36-item, generic health survey that provides scores for eight health domains (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health) and two summary scores; the physical component summary (PCS) score and the mental component summary (MCS) score. Higher scores indicate a better health state.

    Measured: From time of enrollment for up to 7 years

14. Norfolk Quality of Life-Diabetic Neuropathy total score (overall and in patients initiating a treatment with eplontersen)

    The Norfolk QOL-DN is a 35-item, disease-specific instrument that provides scores for five domains (symptoms, large fiber neuropathy, small fiber neuropathy, autonomic neuropathy, and activities of daily living) and a total score. Higher scores indicate a worse health state.

    Measured: From time of enrollment for up to 7 years

15. Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (overall and in patients initiating a treatment with eplontersen)

    The KCCQ is a 23-item, disease-specific questionnaire that assesses seven domains (physical limitations, symptom stability, symptom frequency, symptom burden, self-efficacy, quality of life, and social limitation) and provides three summary scores (total symptom score, clinical summary score, and overall summary score). Higher scores indicate a better health state.

    Measured: From time of enrollment for up to 7 years

16. New York Heart Association (NYHA) classification (overall and in patients initiating a treatment with eplontersen)

    I=No symptoms; II=Symptoms with ordinary physical activity; III=Symptoms with less than ordinary physical activity; IV=Symptoms at rest.

    Measured: From time of enrollment for up to 7 years

17. National Amyloidosis Centre (NAC) ATTR staging or Mayo staging (overall and in patients initiating a treatment with eplontersen)

    For NAC staging, Stage I: N-terminal pro-brain natriuretic peptide (NT-proBNP) ≤3000 ng/L and estimated glomerular filtration rate (eGFR) ≥45 ml/min; Stage III: NT-proBNP >3000 ng/L and eGFR <45 ml/min; Stage IV:NT-proBNP ≥10,000 ng/L; Stage II: remainder of patients

    For Mayo staging, Stage I: Both and biomarker values are below the established thresholds; Stage II: Either troponin T or NT-proBNP is above the threshold; Stage III: Both troponin T and NT-proBNP biomarker values are above the threshold.

    Biomarker Thresholds: Troponin T: >0.05 mg/mL and NT-proBNP: >3000 pg/mL.

    Measured: From time of enrollment for up to 7 years

18. Familial amyloid polyneuropathy (FAP) (Coutinho) staging (overall and in patients initiating a treatment with eplontersen)

    Stage 0: No symptoms; Stage I: Unimpaired ambulation; mostly mild sensory, motor and autonomic neuropathy in the lower limbs; Stage II: Assistance with ambulation required, mostly moderate impairment progression to the lower limbs, upper limbs, and trunk; Stage III: Wheelchair-bound or bedridden; severe sensory, motor, and autonomic involvement of all limbs.

    Measured: From time of enrollment for up to 7 years

19. Polyneuropathy disability (PND) score (overall and in patients initiating a treatment with eplontersen)

    Stage 0=No symptoms; Stage I=Sensory disturbances but preserved walking capabilities; Stage II=Impaired walking capacity, but ability to walk without a stick or crutches; Stage IIIA=Walking with help of 1 stick or crutch; Stage IIIB=Walking with the help of 2 sticks or crutches; Stage IV=confined to wheel chair or bedridden.

    Measured: From time of enrollment for up to 7 years

20. Left Ventricular Ejection Fraction (overall and in patients initiating a treatment with eplontersen)

    Left Ventricular Ejection Fraction will be measured in overall and in patients initiating a treatment with eplontersen

    Measured: From time of enrollment for up to 7 years

21. 6-minute walk test (overall and in patients initiating a treatment with eplontersen)

    To address this objective, the distance walked in 6 minutes will be measured.

    Measured: From time of enrollment for up to 7 years

22. Charlson comorbidity index (CCI) and CCI components (overall and in patients initiating a treatment with eplontersen)

    In order to address CCI, most recent score and all CCI componenet will be measured

    • Myocardial infarction
    • Congestive heart failure
    • Peripheral vascular disease
    • Cerebrovascular disease
    • Dementia
    • Chronic pulmonary disease
    • Rheumatic disease
    • Peptic ulcer disease
    • Diabetes (None, Without chronic complications, With chronic complications)
    • Hemiplegia or paraplegia
    • Renal disease
    • Any malignancy, including lymphoma and leukemia, except malignant neoplasm of skin (None, Localized, Metastatic)
    • Liver disease (None, Mild, Moderate, Severe)
    • Metastatic solid tumor
    • Acquired immune deficiency syndrome (AIDS) / Human immunodeficiency virus (HIV)

    Measured: From time of enrollment for up to 7 years

23. Other comorbidities of interest (overall and in patients initiating a treatment with eplontersen)

    In order to address this objective, the following information will be collected:

    • Percentage of patients with depression
    • Percentage of patients with fibromyalgia
    • Percentage of patients with paraproteinemia

    Measured: From time of enrollment for up to 7 years

24. Healthcare resource utilization (overall and in patients initiating a treatment with eplontersen)

    In order to address this objective, the following information will be collected:

    • Number of emergency department visits
    • Number of outpatient visits
    • Inpatient care/hospitalization general ward (non-intensive): number of inpatient stays, number of bed days
    • Inpatient care/hospitalization intensive ward: number of inpatient stays, number of bed days

    Measured: From time of enrollment for up to 7 years

25. Mortality (overall and in patients initiating a treatment with eplontersen)

    Mortality during study follow-up (all-cause, related to ATTR amyloidosis), overall and by NYHA/NAC or Mayo/FAP stage

    Measured: Throughout study follow-up (up to 7 years)

26. Liver Disease and Live Transplant

    • Liver disease (for patients with mild, moderate or severe liver disease: Child Pugh score, Child Pugh class, ascites, encephalopathy)
    • Liver transplantation (reason for transplant, type of transplant)

    Measured: From time of Enrollment for up to 7 Years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1. First posted20 Jun 2024
2. Study start25 Jun 2024
3. Primary completion31 Dec 2031 (estimated)
4. Study completion31 Dec 2031 (estimated)

Resources

• Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
• Publications (1)Papers the sponsor has linked to this study.
• Other trials for Transthyretin AmyloidosisStudies of the same condition, open and under way.
• More trials run by AstraZenecaThe sponsor's other registered studies.
• What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.