A Study to Evaluate the Safety of mRNA-0184 in Participants With Heart Failure

The study includes a SAD stage and MAD stage; the stages of SAD and MAD may overlap. The SAD stage will begin first, and data from this stage will inform decisions about dose levels in subsequent SAD cohorts and in the MAD stage.

Key Inclusion Criteria:

• Documented diagnosis of heart failure (HF) based on medical records.
• Left ventricular ejection fraction (LVEF) ≥ 35% and < 50% at Screening, or documented within the 3 months before Screening, measured by transthoracic echocardiogram (TTE) or cardiac magnetic resonance imaging (MRI).
• New York Heart Association (NYHA) HF Class I or II.
• On a stable regimen of cardiovascular medication(s) for a duration of at least 4 weeks before Screening.

Key Exclusion Criteria:

• Hospitalized for cardiovascular causes within 3 months before Screening.
• Decompensated HF, acute myocarditis, hypertrophic and/or restrictive/constrictive cardiomyopathy, or moderate or severe valvular heart disease (as classified by echocardiography) at Screening or within the 3 months before Screening. Moderate tricuspid regurgitation is not exclusionary. Congenital heart disease as the primary etiology for heart failure will be excluded.
• Symptoms of angina pectoris at Screening.
• Severe obstructive or restrictive pulmonary pathology, including chronic obstructive pulmonary disease Gold Stage III or IV, current use of oxygen therapy, or Group 1, 3, 4, or 5 pulmonary hypertension. Group 2 pulmonary hypertension is not exclusionary.
• History of sustained ventricular tachycardia or atrial fibrillation/atrial flutter with a ventricular response ≥ 110 beats per minute (bpm) at the time of Screening.
• History of hypersensitivity to any components of the investigational product (IP).
• Participant has received or is expected to receive a COVID-19 vaccination within 7 days of the planned date of IP administration.
• For SAD cohort participants to be rolled over into the MAD stage, have experienced a dose-limiting toxicity (DLT) in a SAD cohort.
• Participation in another clinical study of another IP within 30 days before Screening or within 5 terminal elimination half-lives of the IP, whichever is longer.
• Any other clinically significant medical condition that, in the Investigator's opinion, could interfere with the interpretation of study results or limit the participant's participation in the study, including poorly controlled diabetes mellitus.