NCT06465810

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.

Trial Health

83
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
1,850

participants targeted

Target at P75+ for all trials

Timeline
67mo left

Started Jun 2024

Longer than P75 for all trials

Geographic Reach
7 countries

67 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress26%
Jun 2024Dec 2031

First Submitted

Initial submission to the registry

May 13, 2024

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 20, 2024

Completed
5 days until next milestone

Study Start

First participant enrolled

June 25, 2024

Completed
7.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 29, 2031

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 29, 2031

Last Updated

May 26, 2026

Status Verified

May 1, 2026

Enrollment Period

7.5 years

First QC Date

May 13, 2024

Last Update Submit

May 22, 2026

Conditions

Keywords

AmyloidosisTransthyretinHereditary transthyretin-mediated (hATTR) amyloidosishATTR amyloidosisHereditary ATTR amyloidosisWild-type amyloidosiswtATTR amyloidosisATTRv amyloidosisATTRwt amyloidosisPolyneuropathyFamilial amyloid polyneuropathiesATTRTransthyretin amyloidosisTTR-mediated amyloidosisPolyneuropathiesAmyloid neuropathiesAmyloid neuropathies, familialAmyloidosis, familialEplontersenNon-interventionalObservationalReal-world

Outcome Measures

Primary Outcomes (26)

  • 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

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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)

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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)

    From time of enrollment for up to 7 years

  • 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)

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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.

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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.

    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)

    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)

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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

    From time of enrollment for up to 7 years

  • 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

    Throughout study follow-up (up to 7 years)

  • 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)

    From time of Enrollment for up to 7 Years

Secondary Outcomes (20)

  • 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

  • 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

  • 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

  • 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

  • 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

  • +15 more secondary outcomes

Other Outcomes (3)

  • Risk factors for worsening ATTR progression

    up to 7 years

  • Healthcare costs in patients with ATTR amyloidosis

    Up to 7 years

  • Serious adverse events in patients treated with ATTR amyloidosis treatments

    Up to 7 years

Study Arms (3)

ATTR cardiomyopathy (ATTR-CM)

Patients with ATTR-CM at enrollment

Drug: Treatment of transthyretin (ATTR) amyloidosis in observational study setting

Hereditary polyneuropathy (ATTRv-PN)

Patients with ATTRv-PN at enrollment

Drug: Treatment of transthyretin (ATTR) amyloidosis in observational study setting

ATTR-Mixed

Patients with a mixed ATTR amyloidosis phenotype

Drug: Treatment of transthyretin (ATTR) amyloidosis in observational study setting

Interventions

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

ATTR cardiomyopathy (ATTR-CM)ATTR-MixedHereditary polyneuropathy (ATTRv-PN)

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Patients with a diagnosis of amyloid transthyretin (ATTR) amyloidosis

You may qualify if:

  • 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)

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (67)

Research Site

La Jolla, California, 92037, United States

RECRUITING

Research Site

Los Angeles, California, 90095, United States

RECRUITING

Research Site

San Francisco, California, 94025, United States

RECRUITING

Research Site

San Francisco, California, 94143, United States

RECRUITING

Research Site

New Haven, Connecticut, 06510, United States

RECRUITING

Research Site

Washington D.C., District of Columbia, 20010, United States

RECRUITING

Research Site

Chicago, Illinois, 60637, United States

RECRUITING

Research Site

Indianapolis, Indiana, 06200, United States

RECRUITING

Research Site

Boston, Massachusetts, 02111, United States

RECRUITING

Research Site

Boston, Massachusetts, 02114, United States

NOT YET RECRUITING

Research Site

Boston, Massachusetts, 02115, United States

RECRUITING

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Rochester, Minnesota, 55905, United States

RECRUITING

Research Site

Kansas City, Missouri, 64111, United States

RECRUITING

Research Site

St Louis, Missouri, 63110, United States

RECRUITING

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New Brunswick, New Jersey, 08901, United States

RECRUITING

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Manhasset, New York, 11030, United States

RECRUITING

Research Site

New York, New York, 10027, United States

RECRUITING

Research Site

New York, New York, 10029, United States

RECRUITING

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Durham, North Carolina, 27710, United States

RECRUITING

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Portland, Oregon, 97239, United States

NOT YET RECRUITING

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Danville, Pennsylvania, 17822, United States

RECRUITING

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Philadelphia, Pennsylvania, 19104, United States

RECRUITING

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Philadelphia, Pennsylvania, 19107, United States

RECRUITING

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Greenville, South Carolina, 29607, United States

RECRUITING

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Germantown, Tennessee, 38138, United States

RECRUITING

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Nashville, Tennessee, 37214, United States

RECRUITING

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Dallas, Texas, 75246, United States

RECRUITING

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Richmond, Virginia, 23298, United States

RECRUITING

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Seattle, Washington, 98915, United States

RECRUITING

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Milwaukee, Wisconsin, 53226, United States

RECRUITING

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Vancouver, British Columbia, V5Z 1M9, Canada

RECRUITING

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Vancouver, British Columbia, V6Z 1Y6, Canada

RECRUITING

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Halifax, Nova Scotia, B3RIV9, Canada

RECRUITING

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London, Ontario, N6A 5A5, Canada

RECRUITING

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Toronto, Ontario, M2J 4W8, Canada

RECRUITING

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Rimouski, Quebec, G5L 5T1, Canada

NOT YET RECRUITING

Research Site

Beijing, Beijing Municipality, 100034, China

NOT YET RECRUITING

Research Site

Beijing, Beijing Municipality, 100191, China

RECRUITING

Research Site

Beijing, Beijing Municipality, 100730, China

RECRUITING

Research Site

Fuzhou, Fujian, 350005, China

NOT YET RECRUITING

Research Site

Guangzhou, Guangdong, 510080, China

NOT YET RECRUITING

Research Site

Guangzhou, Guangdong, 510515, China

NOT YET RECRUITING

Research Site

Changsha, Hunan, 410013, China

RECRUITING

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Nanchang, Jiangxi, 330000, China

RECRUITING

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Shanghai, Shanghai Municipality, 200040, China

RECRUITING

Research Site

Hebei Sheng, Shijiazhuang, 050000, China

NOT YET RECRUITING

Research Site

Shaanxi, Xi'An, 710061, China

RECRUITING

Research Site

Würzburg, Bavaria, DE-97072, Germany

NOT YET RECRUITING

Research Site

Frankfurt am Main, Hesse, 60590, Germany

RECRUITING

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Hanover, Lower Saxony, 30625, Germany

RECRUITING

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Aachen, North Rhine-Westphalia, 52074, Germany

RECRUITING

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Cologne, North Rhine-Westphalia, 50937, Germany

RECRUITING

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Mainz, Rhineland-Palatinate, 55131, Germany

RECRUITING

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Homburg, Saarland, 66421, Germany

RECRUITING

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Berlin, 10117, Germany

RECRUITING

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Yamagata, Japan

ACTIVE NOT RECRUITING

Research Site

Huelva, Andalusia, 21005, Spain

RECRUITING

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Cataluna, Barcelona, 08907, Spain

NOT YET RECRUITING

Research Site

Bilbao, Basque Country, 48013, Spain

RECRUITING

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Las Palmas de Gran Canaria, Canary Islands, 35010, Spain

RECRUITING

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Salamanca, Castille and León, 37007, Spain

RECRUITING

Research Site

Barcelona, Catalu A, 08035, Spain

RECRUITING

Research Site

Majadahonda, Madrid, 28222, Spain

NOT YET RECRUITING

Research Site

Islas Baleares, Palma de Mallorca, 07198, Spain

RECRUITING

Research Site

Birmingham, West Midlands, B15 2GW, United Kingdom

RECRUITING

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Glasgow, G51 4TF, United Kingdom

RECRUITING

Research Site

London, NW3 2QG, United Kingdom

RECRUITING

Related Publications (1)

  • Gillmore JD, Hahn K, Smith JG, Conceicao I, Tian Z, Grogan M, Pao C, Wittbrodt E, Jarbrink K, Papas MA, Davis MK. Rationale and Design of ANTHOLOGY: An ATTR Amyloidosis Real-World Evidence Program Aiming to Address Gaps in Amyloidosis Care. Cardiol Ther. 2025 Sep;14(3):477-490. doi: 10.1007/s40119-025-00402-y. Epub 2025 Mar 19.

MeSH Terms

Conditions

Amyloidosis, Hereditary, Transthyretin-RelatedAmyloidosisAmyloid Neuropathies, FamilialPolyneuropathiesAmyloid NeuropathiesAmyloidosis, Familial

Interventions

Amyloid

Condition Hierarchy (Ancestors)

Proteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesNervous System DiseasesPeripheral Nervous System DiseasesNeuromuscular DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMetabolism, Inborn Errors

Intervention Hierarchy (Ancestors)

Multiprotein ComplexesMacromolecular SubstancesProteinsAmino Acids, Peptides, and Proteins

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 13, 2024

First Posted

June 20, 2024

Study Start

June 25, 2024

Primary Completion (Estimated)

December 29, 2031

Study Completion (Estimated)

December 29, 2031

Last Updated

May 26, 2026

Record last verified: 2026-05

Data Sharing

IPD Sharing
Will share

Plan to share only the redacted CSR synopsis

Shared Documents
CSR
Time Frame
AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Access Criteria
When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.
More information

Locations