CLEOPATTRA: A Research Study to Look at the Effects of Treatment With a Medicine Called Coramitug (NNC6019-0001) in People With Heart Failure Due to Transthyretin Amyloid (ATTR) Amyloidosis

Inclusion Criteria:

• Male or female.

• Age 18 years or above at the time of signing the informed consent.

• Have an established diagnosis of ATTR-CM (wild-type ATTR [ATTRwt] or variant ATTR [ATTRv]), with cardiac amyloid infiltration, increased left ventricular (LV) wallthickness, and HF.

Note: Target ATTRv recruitment is approximately 15 percent of the study population.

a. Cardiac amyloid infiltration demonstrated by: i. Cardiac biopsy positive for TTR amyloid, OR ii. Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylene diphosphonate (HMDP) nuclear medicine imaging with single-photon emission computed tomography (SPECT) or SPECT/CT (preferably) combined with an extracardiac biopsy positive for TTR amyloid, OR iii. Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP nuclear medicine imaging with SPECT or SPECT/CT (preferably) combined with normal serum free light chain ratio, and negative serum and urine protein electrophoresis with immunofixation (SPIE & UPIE)/or mass spectrometry based methods including mass fixation).

Notes:

• Non-invasive diagnostic pathway will be confirmed by a centralised expert review.

• Bone tracer nuclear medicine imaging with SPECT or SPECT/CT (preferably) will beconducted using 99m-technetium (Tc)-labelled pyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeled hydroxymethylene diphosphonate (99mTc-HMDP).

• The eGFR adjusted acceptable serum free light chain ratio.

• Patients with Grade 2 or 3 cardiac uptake at PYP/DPD/HDMP nuclear imaging with SPECTor SPECT/CT (preferably) and evidence of monoclonal gammopathy of undeterminedsignificance (MGUS; based on serum and urine protein electrophoresis and serum freelight chains) will require endomyocardial biopsy with typing using mass spectrometryor immunohistochemistry to confirm presence of TTR protein in tissue.

• Timing of serum free light chain ratio, SPIE, UPIE and mass spectrometry-basedmethods including mass fixation should be within 12 months of SPECT or SPECT/CTnuclear imaging. b. Increased LV wall thickness, as assessed by centralised review ofechocardiography, showing interventricular septal wall thickness greater than orequal to 12 millimeter (mm). c. Chronic HF (New York Heart Association [NYHA] Class I-IV): i. At least 1documented hospitalisation for HF, OR ii. History of HF manifested by signs orsymptoms of volume overload or elevated intracardiac pressures (e.g., elevatedjugular venous pressure, shortness of breath, signs of pulmonary congestion on x-rayor auscultation, or peripheral oedema that required or requires ongoing treatmentwith a diuretic).

• Expected to be on stable cardiovascular medical therapy (defined as no greaterthan 50 percent dose adjustment and no categorical changes of medications),with the exception of diuretics, 4 weeks prior to the randomisation visit.

• Completed more than 50 meters on the 6MWT at screening.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention(s) or related products.

• Current or previous participation (dosing with active treatment) in a study for aninvestigational ATTR depleting drug or ATTR gene editing therapy.

• Total bilirubin greater than 3 times the upper limit of normal (ULN) at screening.

• Current diagnosis or history of amyloid light chain, other non-ATTR amyloidosis,known leptomeningeal amyloidosis, or multiple myeloma.

• HF not primarily caused by ATTR-CM (e.g., due to hypertension, valvular heartdisease, or ischemic heart disease in the opinion of the investigator).

• Currently hospitalised or hospitalised within 14 days prior to screening.

• Currently treated with positive inotropic medication.

• Uncorrected, severe, haemodynamically significant, left-sided heart valve disease.

• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack,coronary revascularisation, cardiac device implantation, cardiac valve repair, ormajor surgery within 60 days of screening.

• Prior solid organ transplant or planned solid organ transplant during the study.

• Left ventricular ejection fraction (LVEF) less than 30 percent as assessed bycentralised review of echocardiography.

• Presence or history of malignant neoplasm (other than basal or squamous cell skincancer, in situ carcinomas of the cervix, carcinoma in situ/high-grade prostaticintraepithelial neoplasia [PIN], low-risk prostate cancer, or on stable therapy forprostate cancer) within 3 years before screening.

• End-stage renal disease (estimated glomerular filtration rate [eGFR] less than 15mL/min/1.73 m^2 at screening, or chronic/intermittent haemodialysis or peritonealdialysis).