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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).

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

RD-clinical-information-Japan@astrazeneca.com

Ageishi Yuji

Astrazeneka K.K

3-1, Ofuka-cho, Kita-ku, Osaka-shi, Osaka

+81-6-4802-3600

RD-clinical-information-Japan@astrazeneca.com

Suspended

June. 24, 2026

Interventional

randomized controlled trial

double blind

placebo control

parallel assignment

treatment purpose

- 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).

- 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.

Both

Transthyretin Amyloid Cardiomyopathy (ATTR-CM)

Drug: Eplontersen
Eplontersen delivered subcutaneously, once every 4 weeks

Biological: ALXN2220
ALXN2220 delivered intravenously, once every 4 weeks

Other: Placebo
Placebo delivered intravenously, once every 4 weeks

CPET peak VO2 [Time Frame: 52 week]
Change from baseline in CPET peak VO2 at week 52

+81-3-3353-1211

No

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All requests 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.

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