Clinical Trials

Inclusion Criteria:

• Informed consent obtained before any study-related activities. Study-related activities are any procedures that are carried out as part of the study, including activities to determine suitability for the study.
• Male or female.
• Age ≥ 18 to < 85 years at the time of signing informed consent.
• Have an established diagnosis of ATTR CM with either wild-type TTR or hereditary TTR genotype as per local standardsa.
• Expected to be on stable doses of cardiovascular medical therapy 6 weeks prior to the randomisation visit.
• Known end-diastolic interventricular septal wall thickness ≥ 12 mm.
• Presently classified as New York Heart Association (NYHA) Class II-III.
• NT-proBNP concentration ≥ 650 pg/mL in sinus cardiac rhythm and > 1000 pg/mL in atrial fibrillation at screening.
• Completed ≥ 150 meters to ≤ 450 meters on the 6MWT at screening.
• Absolute neutrophil count ≥ 2.0 × 10^9 /L; platelet count ≥ 120 × 10^9 /L at screening.
• Aspartate transaminase (AST) and alanine transaminase (ALT) levels ≤ 2.5 × the upper limit of normal (ULN) and total bilirubin ≤ 2 × ULN at screening.
• Estimated glomerular filtration rate (eGFR) ≥ 25 mL/min/1.73 m^2 at screening.

Exclusion Criteria:

• Known or suspected hypersensitivity to study intervention(s) or related products.
• Previous dosing in this study.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of childbearing potential and not using highly effective contraceptive method. 
• Use of another approved or non-approved investigational medicinal product within 30 days or 5 half-lives of the investigational medicinal product (whichever is longer) before screening.
• Any disorder, which in the investigator’s opinion might jeopardise participant’s safety or compliance with the protocol.
• Current diagnosis or history of amyloid light chain or other non-ATTR amyloidosis.
• Cardiomyopathy not primarily caused by ATTR CM, for example, cardiomyopathy due to hypertension, valvular heart disease, or ischemic heart disease.
• A prior solid organ transplant.
• Planned solid organ transplant during the study.
• Presence or history of malignant neoplasm (other than basal or squamous cell skin cancer, insitu carcinomas of the cervix, or in-situ/high grade prostatic intraepithelial neoplasia (PIN) or low-grade prostate cancer) within 5 years before screening.
• Current treatment with calcium channel blockers with conduction system effects (e.g., verapamil, diltiazem). The use of dihydropyridine calcium channel blockers is allowed. The use of digoxin will only be allowed if required for management of atrial fibrillation with rapid ventricular response.
• Acute coronary syndrome, unstable angina, stroke, transient ischemic attack (TIA), coronary revascularisation, cardiac valve repair, or major surgery within 3 months of screening.
• Body weight > 120 kg (264.6 lb) at screening.
• Evidence of current or chronic hepatitis C virus or hepatitis B virus infection.
• History of or known seropositivity for human immunodeficiency virus (HIV).
• International normalised ratio (INR) >1.5 (unless participant is on anticoagulant therapy, in which case excluded if INR >3.5) .
• History of contrast allergy or adverse reactions to gadolinium-containing agents. Definitions:
  • Non-invasive diagnostic pathway will be confirmed by a centralised expert review;
  • Medical history/records are accepted;
  • Vitamin K antagonists; i.e. warfarin, acenocoumarol etc.;
  • Criterion not applicable for participants on therapy with direct-acting oral anticoagulants (DOACs).

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 9/28/23. Questions regarding updates should be directed to the study team contact.