Transthyretin Amyloid Cardiomyopathy (ATTR-CM)Phase 2ATTRiumphNCT07608354
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
A Phase 2 study testing Eplontersen and ALXN2220 in people with Transthyretin Amyloid Cardiomyopathy (ATTR-CM), run by AstraZeneca at 76 sites in 10 countries.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Transthyretin Amyloid Cardiomyopathy (ATTR-CM)
- What is being tested?
- Eplontersen and ALXN2220
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 326 participants
- Where
- 76 sitesin 10 countries
- Study dates
- 11 Jun 2026to 6 Feb 2029
- Phase
- Phase 2
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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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).
Who cannot join
- 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.
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- 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.
- History of solid organ transplantation or ventricular assist device or listing for heart transplantation at Screening. Note: prior history of planned corneal transplant is not an exclusion criterion.
- Suspected or known intolerance/allergy to proteins or any components of the study intervention.
- Any of the following results conducted at screening:
- 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.
- 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.
- Multiple myeloma, lymphoma, leukemia, or any malignancy or clonal stem cell disorder within the past 5 years (except basal cell or squamous epithelial carcinomas of the skin, melanoma in situ or cervical carcinoma in situ that have been curatively resected, Stage I cancer in remission, or adequately treated prostate cancer stage I, IIA, or IIB with Gleason score ≤ 3+4 and prostate-specific antigen < 20 ng/mL).
- Any prior treatment with an ATTR amyloid depleter or a TTR gene silencing agent approved or in clinical development.
- Participated in a structured exercise training programme within the 1 month prior to Screening or planned to start during the trial.
- Participation in another investigational clinical study or intake of another investigational drug within 30 calendar days or 5 half-lives of the IMP, whichever is longer before signing the ICF.
- Judgement by the Investigator that the participant should not participate in the study if the participant has a known medical or psychological condition or other risk factor that might interfere with the participant's full participation in the study, pose any additional risk for the participant, or confound the assessment of the participant or outcome of the study.
- Previous enrolment or randomisation in the present study.
Trial locations and contacts
76 sites in 10 countries.
76 sites in 10 countries
United States24 sites
Research Site
Aurora, Colorado, 80045
Research Site
Boston, Massachusetts, 02115
Research Site
Chapel Hill, North Carolina, 27599
Research Site
Chicago, Illinois, 60637
Research Site
Cleveland, Ohio, 44195
Research Site
Dallas, Texas, 75390
Research Site
Danville, Pennsylvania, 17822
Research Site
Durham, North Carolina, 27710
Research Site
Falls Church, Virginia, 22042
Research Site
Germantown, Tennessee, 38138
Research Site
Houston, Texas, 77030
Research Site
Jacksonville, Florida, 32224
Research Site
Kansas City, Missouri, 64111
Research Site
La Jolla, California, 92037
Research Site
Miami, Florida, 33176
Research Site
New York, New York, 10032
Research Site
Philadelphia, Pennsylvania, 19104
Research Site
Portland, Oregon, 97239
Research Site
Salt Lake City, Utah, 84132
Research Site
San Francisco, California, 94115
Research Site
St Louis, Missouri, 63110
Research Site
Stanford, California, 94305
Research Site
Washington D.C., District of Columbia, 20010
Research Site
Weston, Florida, 33331
Italy9 sites
Research Site
Bologna, 40138
Research Site
Florence, 50134
Research Site
Milan, 20138
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Padova, 35128
Research Site
Pavia, 27100
Research Site
Pisa, 56124
Research Site
Torino, 10154
Research Site
Torrette - Ancona, 60126
Research Site
Trieste, IT-34149
Germany8 sites
Research Site
Berlin, 10117
Research Site
Cologne, 50937
Research Site
Essen, 45147
Research Site
Hamburg, 22767
Research Site
Heidelberg, 69120
Research Site
Homburg, 66421
Research Site
München, 81377
Research Site
Münster, 48149
Spain8 sites
Research Site
Barcelona, 08035
Research Site
Jaén, 23007
Research Site
L'Hospitalet de Llobregat, 08907
Research Site
Majadahonda, 28222
Research Site
Málaga, 29010
Research Site
Pamplona, 31008
Research Site
Salamanca, 37007
Research Site
Valencia, 46010
Canada6 sites
Research Site
Calgary, Alberta, T2N 4Z6
Research Site
Halifax, Nova Scotia, B3H 3A7
Research Site
London, Ontario, N6A 5A5
Research Site
Montreal, Quebec, H1T 1C8
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Toronto, Ontario, M5G 2C4
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Vancouver, British Columbia, V6Z 1Y6
China6 sites
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Beijing, 100034
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Beijing, 100730
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Changsha, 410012
Research Site
Chongqing, 400042
Research Site
Guangzhou, 510080
Research Site
Hangzhou, 310009
Japan5 sites
Research Site
Bunkyō City, 113-8431
Research Site
Kurume-shi, 830-0011
Research Site
Sapporo, 060-8543
Research Site
Shinjuku-ku, 160-8582
Research Site
Suita, 565-8565
France4 sites
Research Site
Créteil, 94010
Research Site
Marseille, 13005
Research Site
Rennes, 35033
Research Site
Toulouse, 31059
Sweden4 sites
Research Site
Gothenburg, 413 45
Research Site
Lund, 22242
Research Site
Stockholm, 171 64
Research Site
Uppsala, 751 85
United Kingdom2 sites
Research Site
London, NW10 2PB
Research Site
London, NW3 2QG
About this study
Official title: 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)
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).
Read the detailed description
This is a Phase IIb, multicenter, double-blind study in 326 participants, who will be randomized to receive either eplontersen and ALXN2220 or eplontersen and placebo once every four weeks. Participants will also receive daily supplemental doses of the recommended daily allowance of vitamin A.
- Being tested
- Eplontersen, ALXN2220, Placebo
- Keywords
- Transthyretin amyloid cardiomyopathy, ATTR-CM, Eplontersen, ALXN2220
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EplontersenDrug
Eplontersen delivered subcutaneously, once every 4 weeks
ALXN2220Biological
ALXN2220 delivered intravenously, once every 4 weeks
PlaceboOther
Placebo delivered intravenously, once every 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Eplontersen and ALXN2220 | Experimental | Subcutaneous eplontersen and intravenous ALXN2220 every 4 weeks Receives: Drug: Eplontersen; Biological: ALXN2220 |
| Eplontersen and placebo | Placebo comparator | Subcutaneous eplontersen and intravenous placebo every 4 weeks Receives: Drug: Eplontersen; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cardiopulmonary exercise test peak VO2
Change from baseline in Cardiopulmonary exercise test peak VO2 at week 52
Measured: 52 week
Secondary outcomes (3)
Extracellular volume
Change from baseline in Extracellular volume (subgroup) at week 52
Measured: 52 week
NT-proBNP
Change from baseline in NT-proBNP at week 52
Measured: 52 week
Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score
Change from baseline in Kansas City Cardiomyopathy Questionnaire-Clinical Summary Score at week 52.
The minimum score is 0 and maximum score is 100. Higher scores indicate better health status.
Measured: 52 week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 May 2026
- Study start11 Jun 2026
- Primary completion6 Feb 2029 (estimated)
- Study completion6 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin Amyloid Cardiomyopathy (ATTR-CM)Studies 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.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 326 participants (estimated)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07608354
- Sponsor's protocol ID
- D8456C00001
- Acronym
- ATTRiumph
- Status last verified
- Jul 2026
- First submitted
- 12 May 2026
- Last updated
- 14 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.