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.

1. Cardiac amyloid infiltration demonstrated by:

• Cardiac biopsy positive for TTR amyloid, OR

• Grade 2 or 3 cardiac uptake at pyrophosphate (PYP)/diphosphono-1,2-propanodicarboxylic acid (DPD)/ hydroxymethylenediphosphonate (HMDP) scintigraphy with single-photon emission computedtomography (SPECT/CT) combined with an extracardiac biopsy positive for TTRamyloid, OR

• Grade 2 or 3 cardiac uptake at PYP/DPD/HMDP scintigraphy with SPECT/CT combinedwith normal serum free light chain ratio, and negative serum and urine proteinelectrophoresis with immunofixation (SPIE & UPIE). Notes:

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

• Bone tracer scintigraphy will be conducted using 99m-technetium (Tc)-labelledpyrophosphate (99mTc-PYP), 99mTc-labelled 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD), or 99mTc-labeledhydroxymethylene diphosphonate (99mTc-HMDP).

2. Increased LV wall thickness, as assessed by centralised review of echocardiography,showing interventricular septal wall thickness greater than or equal to 12millimeter (mm).

3. Chronic HF (New York Heart Association [NYHA] Class I-IV) requiring ongoingtreatment with a loop diuretic with:

• At least 1 documented hospitalisation for HF, OR

• History of HF manifested by signs or symptoms of volume overload or elevatedintracardiac pressures (e.g., elevated jugular venous pressure, shortness ofbreath, signs of pulmonary congestion on x-ray or auscultation, or peripheraloedema).

• 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.

Note: Pre-existing echocardiogram up to 2 years old may be used.

• 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).