New drug duo aims to stop rare heart disease in its tracks

NCT ID NCT07608354

Disease control Sponsor: AstraZeneca Source: ClinicalTrials.gov ↗

First seen Jun 25, 2026 · Last updated Jul 15, 2026 · Updated 3 times

Summary

This phase 2b trial tests whether adding ALXN2220 to eplontersen works better than eplontersen alone for adults with transthyretin amyloid cardiomyopathy (ATTR-CM), a condition where abnormal proteins build up in the heart. About 326 participants will receive either the combination or eplontersen plus a placebo. The main goal is to see if the combo improves exercise capacity after one year.

What this could mean

Our plain-language read of the trial. This is informational only, not medical advice or a prediction.

Active substance: eplontersen (a drug) and ALXN2220 (a biologic)
What this could lead to: If successful, this combination could slow or stop heart damage from ATTR-CM, improving exercise ability and quality of life.
What could go wrong: This is a mid-stage trial with only 326 participants, so results may not apply to everyone. The added benefit of ALXN2220 over eplontersen alone is unproven, and side effects are possible.

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Study facts

What this study's own registry entry says, in plain language.

Phase

Phase 2

Tests whether the treatment actually works, and watches for side effects, in a larger group.

Participants

About 326 people

The number the study aims to enrol. It can still change while the study runs.

Started

Jun 2026

Expected to finish

Feb 2029

An estimate. End dates often move.

Lead sponsor

A company

The lead sponsor is a pharmaceutical, biotech, or medical-device company.

Who can take part

This study's own entry requirements. Only the study team can say for certain whether you qualify.

Ages

18 to 85 years

Sex

Anyone

Healthy volunteers

Not accepted

This study is not open to healthy volunteers. The entry requirements below say who it is open to.

Show the full entry requirements

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Capable of giving informed consent. Inclusion Criteria: * 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: 1. Endomyocardial biopsy with confirmatory TTR amyloid typing OR 2. Grade 2 or 3 cardiac uptake on 99mTc scintigraphy in the absence of monoclonal gammopathy OR 3. 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: 1. Able to exercise to near exhaustion during CPET as exhibited by RER ≥ 1.0 during symptom-limited CPET conducted during screening. 2. 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). Exclusion Criteria: * 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. * 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: 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. * 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.

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Conditions

The condition(s) this trial relates to.

wild type ATTR amyloidosis

As listed by the trial registrant

The condition terms exactly as the trial's registrant entered them.

Transthyretin amyloid cardiomyopathy (attr-CM)

Contacts and locations

Locations

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 4Z6, 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, N6A 5A5, 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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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
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Sapporo, 060-8543, Japan
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Shinjuku-ku, 160-8582, Japan
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Suita, 565-8565, Japan
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Barcelona, 08035, Spain
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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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Uppsala, 751 85, Sweden
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London, NW10 2PB, United Kingdom
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London, NW3 2QG, United Kingdom

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