A Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo for Adults Participants With ATTR-CM
ATTRiumph
A Phase IIb, Randomised, Double-blind, Placebo-controlled, Multicentre Study to Evaluate the Efficacy and Safety of Concomitant Use of Eplontersen and ALXN2220 Compared With Eplontersen and Placebo in Adult Participants With Transthyretin-Mediated Amyloid Cardiomyopathy (ATTR-CM)
1 other identifier
interventional
326
10 countries
78
Brief Summary
The purpose of this randomised, double-blind, placebo-controlled, multicenter study is to evaluate the efficacy and safety of concomitant use of eplontersen and ALXN2220 compared with eplontersen and placebo in adult participants with Transthyretin-mediated amyloid cardiomyopathy (ATTR-CM).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_2
Started Jun 2026
78 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
May 12, 2026
CompletedFirst Posted
Study publicly available on registry
May 27, 2026
CompletedStudy Start
First participant enrolled
June 30, 2026
ExpectedPrimary Completion
Last participant's last visit for primary outcome
February 23, 2029
Study Completion
Last participant's last visit for all outcomes
February 23, 2029
June 10, 2026
June 1, 2026
2.7 years
May 12, 2026
June 9, 2026
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Cardiopulmonary exercise test peak VO2
Change from baseline in Cardiopulmonary exercise test peak VO2 at week 52
52 week
Secondary Outcomes (3)
Extracellular volume
52 week
NT-proBNP
52 week
Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score
52 week
Study Arms (2)
Eplontersen and ALXN2220
EXPERIMENTALSubcutaneous eplontersen and intravenous ALXN2220 every 4 weeks
Eplontersen and placebo
PLACEBO COMPARATORSubcutaneous eplontersen and intravenous placebo every 4 weeks
Interventions
Eplontersen delivered subcutaneously, once every 4 weeks
Eligibility Criteria
You may qualify if:
- Participant must be ≥ 18 years to ≤ 85 years at the time of signing the informed consent.
- Participants who have a diagnosis of ATTR-CM with either wild-type or variant TTR genotype based on 1 of the following:
- Endomyocardial biopsy with confirmatory TTR amyloid typing OR
- Grade 2 or 3 cardiac uptake on 99mTc scintigraphy in the absence of monoclonal gammopathy OR
- Grade 2 or 3 cardiac uptake on 99mTc scintigraphy AND confirmatory TTR amyloid typing in the presence of monoclonal gammopathy.
- NYHA Class I to III at Screening and life expectancy of ≥ 1 year as per the Investigator's judgement.
- End-diastolic IVST ≥ 12 mm on echocardiography.
- NT-proBNP ≥ 600pg/mL for participants without ongoing atrial fibrillation/flutter at Screening or NT-proBNP ≥ 1200pg/mL for participants with ongoing atrial fibrillation/flutter at Screening.
- Able to complete symptom-limited maximal CPET at Screening based on the following test criteria:
- Able to exercise to near exhaustion during CPET as exhibited by RER ≥ 1.0 during symptom-limited CPET conducted during screening.
- If participant does not achieve RER ≥1.0, the CPET may be repeated once, at least 48 hours but less than 2 weeks (but before randomization) after the initial test.
- Treated according to locally recognised guidelines on standard-of-care treatment for patients with HF. Therapy should have been individually optimised and stable for ≥ 4 weeks (except diuretics) and include, unless contraindicated or not tolerated, treatment of high BP (targeting SBP \< 130 mmHg as suggested in 2022 American College of Cardiology/American Heart Association/Heart Failure Society of America HF guidelines), and ischaemic heart disease.
- Willingness to adhere to daily self-administered vitamin A supplementation (3000 IU).
You may not qualify if:
- Known leptomeningeal amyloidosis.
- Known light chain (AL) or secondary (amyloid A) amyloidosis, or any other form of systemic amyloidosis.
- Cardiomyopathy not primarily caused by ATTR-CM, for example, cardiomyopathy primarily due to hypertension, valvular heart disease, or ischaemic heart disease per Investigator's assessment.
- Acute coronary syndrome, unstable angina, stroke, transient ischaemic attack, coronary revascularisation, cardiac device implantation, cardiac valve repair, or major surgery within 12 weeks of Screening.
- Uncontrolled hypertension (average resting SBP \> 160 mmHg or DBP \> 100 mmHg at Screening).
- Average resting SBP \< 90 mmHg or symptomatic orthostatic hypotension, despite appropriate treatment, at Screening per Investigator's assessment.
- Uncontrolled ventricular clinically significant cardiac arrhythmia, per Investigator's assessment.
- Left ventricular ejection fraction \< 30% on echocardiography measured locally at Screening.
- Severe pulmonary impairment (SpO₂ \< 92%) defined as resting SpO₂ below 92% on room air, measured by pulse oximetry, indicative of severe lung disease. Participants requiring supplemental oxygen to maintain SpO₂ ≥ 92%.
- Participants with renal failure requiring dialysis.
- Suspected or known intolerance/allergy to proteins or any components of the study intervention.
- Any of the following results conducted at screening:
- i) Haemoglobin \<8g/dL for women or \<9g/dL for men. ii) Platelet count \<125 X10\*9/L or other disorder associated with clinically significant thrombocytopenia.
- iii) ALT \>2.0 X ULN iv) TBL \>2.5 X ULN (participants with known Gilbert's syndrome can be included with TBL \>2.5 X ULN as long as direct bilirubin is ≤ 1.5 X ULN) v) Serum retinol level \< LLN vi) By CKD-EPI formula, eGFR \<20 mL/min/1.73 m2 measured by the central laboratory at Screening.
- Current unstable liver or biliary disease per Investigator's assessment.
- +6 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AstraZenecalead
Study Sites (78)
Research Site
La Jolla, California, 92037, United States
Research Site
San Francisco, California, 94115, United States
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Stanford, California, 94305, United States
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Aurora, Colorado, 80045, United States
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Washington D.C., District of Columbia, 20010, United States
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Jacksonville, Florida, 32224, United States
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Miami, Florida, 33176, United States
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Weston, Florida, 33331, United States
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Chicago, Illinois, 60637, United States
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Boston, Massachusetts, 02115, United States
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Kansas City, Missouri, 64111, United States
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St Louis, Missouri, 63110, United States
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New York, New York, 10032, United States
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Chapel Hill, North Carolina, 27599, United States
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Durham, North Carolina, 27710, United States
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Cleveland, Ohio, 44195, United States
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Portland, Oregon, 97239, United States
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Danville, Pennsylvania, 17822, United States
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Philadelphia, Pennsylvania, 19104, United States
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Germantown, Tennessee, 38138, United States
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Dallas, Texas, 75390, United States
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Houston, Texas, 77030, United States
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Salt Lake City, Utah, 84132, United States
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Falls Church, Virginia, 22042, United States
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Calgary, Alberta, T2N 2T9, Canada
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Vancouver, British Columbia, V6Z 1Y6, Canada
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Halifax, Nova Scotia, B3H 3A7, Canada
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London, Ontario, N6C 2R5, Canada
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Toronto, Ontario, M5G 2C4, Canada
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Montreal, Quebec, H1T 1C8, Canada
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Beijing, 100034, China
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Beijing, 100730, China
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Changsha, 410012, China
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Chongqing, 400042, China
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Guangzhou, 510080, China
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Hangzhou, 310009, China
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Créteil, 94010, France
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Marseille, 13005, France
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Rennes, 35033, France
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Toulouse, 31059, France
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Bad Krozingen, 79189, Germany
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Berlin, 10117, Germany
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Cologne, 50937, Germany
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Essen, 45147, Germany
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Hamburg, 22767, Germany
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Heidelberg, 69120, Germany
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Homburg, 66421, Germany
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München, 81377, Germany
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Münster, 48149, Germany
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Bologna, 40138, Italy
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Florence, 50134, Italy
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Milan, 20138, Italy
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Padova, 35128, Italy
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Pavia, 27100, Italy
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Pisa, 56124, Italy
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Torino, 10154, Italy
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Torrette - Ancona, 60126, Italy
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Trieste, IT-34149, Italy
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Bunkyō City, 113-8431, Japan
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Kurume-shi, 830-0011, Japan
Research Site
Sapporo, 060-8543, Japan
Research Site
Shinjuku-ku, 160-8582, Japan
Research Site
Suita, 565-8565, Japan
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Barcelona, 08035, Spain
Research Site
Jaén, 23007, Spain
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L'Hospitalet de Llobregat, 08907, Spain
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Majadahonda, 28222, Spain
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Málaga, 29010, Spain
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Pamplona, 31008, Spain
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Salamanca, 37007, Spain
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Valencia, 46010, Spain
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Gothenburg, 413 45, Sweden
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Lund, 22242, Sweden
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Stockholm, 171 64, Sweden
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Umeå, 90737, Sweden
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Uppsala, 751 85, Sweden
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London, NW10 2PB, United Kingdom
Research Site
London, NW3 2QG, United Kingdom
MeSH Terms
Interventions
Central Study Contacts
AstraZeneca Clinical Study Information Center
CONTACT
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 12, 2026
First Posted
May 27, 2026
Study Start (Estimated)
June 30, 2026
Primary Completion (Estimated)
February 23, 2029
Study Completion (Estimated)
February 23, 2029
Last Updated
June 10, 2026
Record last verified: 2026-06
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP
- Time Frame
- AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer 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 de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.