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

Recruiting

• Conditions: ATTR; ATTR-CM; ATTR-Mixed; Transthyretin Amyloidosis; hATTR; ATTRv-PN
• Interventions: Drug: Treatment of transthyretin (ATTR) amyloidosis in observational study setting

• Registration Number: NCT06465810
• Lead Sponsor: AstraZeneca

Brief Summary

The MaesTTRo study aims to enroll a global cohort of patients with transthyretin (ATTR) amyloidosis to longitudinally observe the natural course of the disease and describe real-world treatment patterns and outcomes. In addition, information on the effectiveness of ATTR amyloidosis treatments, including eplontersen, which is a ligand-conjugated antisense oligonucleotide gene silencing treatment targeting activity against both the mutant and wild-type TTR protein, will be collected.

Detailed Description

MaesTTRo is an international, longitudinal, non-interventional study of adult patients with transthyretin (ATTR) amyloidosis.

The study plans to enroll a minimum of 1,600 patients with ATTR amyloidosis, including a minimum of 1,500 patients with ATTR cardiomyopathy (ATTR-CM), and a minimum of 100 patients with ATTRv-PN hereditary polyneuropathy.

The enrollment period is expected to last approximately 4 years. The duration of follow-up for each patient will be at least 3 years and up to 7 years depending on the date when the patient is enrolled.

This study design will include both primary and secondary data. Primary data will consist of patient-reported outcome (PRO) questionnaires. Patients will be asked to complete electronic PRO questionnaires at enrollment and every 6 months (±3 months) only during routine visits. Secondary data will consist of demographic, clinical, and treatment information, and will be collected as per routine clinical practice. These data will be abstracted directly from the electronic health record or review of paper charts for each patient and entered in the electronic data capture system. No site visits are required for this study, and patients will not be contacted for data collection outside of routine clinic visits.

For patients enrolled in the United States, a tokenization process (creation of a unique, encrypted identifier called a token, in place of personal identifiable information) will be used to collect additional de-identified data (e.g., healthcare resource use, healthcare costs) from other sources that are part of patients' routine medical care (electronic medical, hospital, or pharmacy records). Only de-identified data will be analyzed. Patients will be given a choice within the informed consent form to opt in or opt out of participating in the tokenization process.

Study Timeline

• Study First Submitted: 2024-05-13
• Study First Submitted QC: 2024-06-13
• Study First Posted: 2024-06-20
• Study Start: 2024-06-25
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-20
• Last Update Posted: 2025-05-21
• Primary Completion: 2031-12-29
• Study Completion: 2031-12-29

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1600

Inclusion Criteria

• Patient willing and able to provide written informed consent to participate in the study
• Confirmed diagnosis of amyloid transthyretin (ATTR) amyloidosis
• Aged ≥18 years at the time of signing the informed consent
• Patient willing and able to participate in collection of electronic patient reported outcomes (PROs)

Exclusion Criteria

• Concurrent participation in any interventional trial for ATTR amyloidosis
• Involvement in the planning and/or conduct of the current study
• Patients with evidence of primary or light chain amyloidosis (AL) or serum protein A amyloidosis (AA)
• Asymptomatic patients with ATTR amyloidosis and asymptomatic ATTR mutation carriers

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
ATTR-Mixed	Treatment of transthyretin (ATTR) amyloidosis in observational study setting	Patients with a mixed ATTR amyloidosis phenotype
ATTR cardiomyopathy (ATTR-CM)	Treatment of transthyretin (ATTR) amyloidosis in observational study setting	Patients with ATTR-CM at enrollment
Hereditary polyneuropathy (ATTRv-PN)	Treatment of transthyretin (ATTR) amyloidosis in observational study setting	Patients with ATTRv-PN at enrollment

Primary Outcome Measures

Name	Time	Method
Findings from Cardiovascular magnetic resonance imaging (CMR) (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Findings from Bone tracer cardiac scintigraphy (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Sural nerve and tibial nerve amplitude (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years
Biomarker results (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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)
Urine test results (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	In order to address this objective, the following test results will be collected: * Urine albumin-creatinine ratio (UACR); * Urine protein creatinine ratio (UPCR)
Norfolk Quality of Life-Diabetic Neuropathy total score (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Demographic characteristics (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	* Age; * Sex as determined by the investigator (male/female); * Race and ethnicity, where allowed
Treatment patterns (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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
Findings from biopsy (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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
Clinical characteristics (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	In order to address this objective, the following clinical characteristics will be assessed: * Modified body mass index (mBMI); * Medical history; * Family history of ATTR; * Time period between the first symptoms to date of diagnosis of ATTR; * Time since diagnosis of ATTR
Findings from Echocardiography (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
ECG variables (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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)
Clinical manifestations (signs and symptoms) of ATTR amyloidosis (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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)
National Amyloidosis Centre (NAC) ATTR staging (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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 II: remainder of patients
Familial amyloid polyneuropathy (FAP) (Coutinho) staging (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Polyneuropathy disability (PND) score (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Left Ventricular Ejection Fraction (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years
6-minute walk test (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years
Charlson comorbidity index (CCI) and CCI components (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years
Other comorbidities of interest (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	In order to address this objective, the following information will be collected: * Percentage of patients with depression; * Percentage of patients with fibromyalgia
Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
New York Heart Association (NYHA) classification (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	I=No symptoms; II=Symptoms with ordinary physical activity; III=Symptoms with less than ordinary physical activity; IV=Symptoms at rest.
Healthcare resource utilization (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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
36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary score (overall and in patients initiating a treatment with eplontersen)	From time of enrollment for up to 7 years	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.
Mortality (overall and in patients initiating a treatment with eplontersen)	Throughout study follow-up (up to 7 years)

Secondary Outcome Measures

Name	Time	Method
Comparison of findings from Cardiovascular magnetic resonance imaging (CMR) in patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: 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.
Comparison of findings from Echocardiography in patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: LV ejection fraction, LV End Diastolic Volume, LV End Systolic Volume LV End Diastolic Dimension, LV End Systolic Dimension, Interventricular Septal, Thickness Diastole, Posterial Wall Thickness 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.
Comparison of ECG variables of patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * Interpretation of the ECG (Normal/Abnormal/Borderline); * Heart rhythm; * Presence of extrasystoles; * Presence of conduction abnormalities; * Evidence of left ventricular hypertrophy (LVH)
Comparison of findings from Bone tracer cardiac scintigraphyin patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: Type of tracer, Heart to contralateral lung ratio (H/CL), Perugini grade, scintigraphy result (Normal/Abnormal), reason for considering the result abnormal.
Comparison of sural nerve and tibial nerve amplitude in patients prescribed eplontersen at any time during the observation eriod to patients on other ATTR treatments	Up to 7 years
Comparison of biomarker results in patients prescribed eplontersen at any time during the observation eriod to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * 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)
Comparison of Familial amyloid polyneuropathy (FAP) (Coutinho) staging in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years	FAP staging: 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.
Comparison of Charlson comorbidity index (CCI) and CCI components in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of other comorbidities of interest in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * Percentage of patients with depression; * Percentage of patients with fibromyalgia
Comparison of healthcare resource utilization in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * 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
Comparison of findings from biopsy in patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * 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
Comparison of 36-Item Short Form Health Survey Version 2 (SF-36v2) Physical Component Summary score in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of Kansas City Cardiomyopathy Questionnaire (KCCQ) overall summary score in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of New York Heart Association (NYHA) classification in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of Left Ventricular Ejection Fraction in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of mortality in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years
Comparison of demographic and clinical characteristics of patients prescribed eplontersen at any time during the observation period to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * Demographics; * mBMI; * Medical history; * Family history of ATTR amyloidosis; * Time period between the first symptoms to date of diagnosis of ATTR amyloidosis; * Time since diagnosis of ATTR amyloidosis
Comparison of urine test results in patients prescribed eplontersen at any time during the observation eriod to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: * Urine albumin-creatinine ratio (UACR); * Urine protein creatinine ratio (UPCR)
Comparison of Clinical manifestations (signs and symptoms) of ATTR amyloidosis in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years	The following outcomes will be compared between patients treated with eplontersen and patients on other ATTR treatments: 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)
Comparison of Norfolk Quality of Life-Diabetic Neuropathy total score in patients prescribed eplontersen to patients on other ATTR treatments	Up to 7 years

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom