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

Moderna

Status and phase: Active, not recruiting; Phase 1

Conditions: Chronic Heart Failure

Treatments: Drug: Placebo; Drug: mRNA-0184

Study type: Interventional

Funder types: Industry

Identifiers

NCT05659264

2022-000784-46 (EudraCT Number)

mRNA-0184-P101

Details and patient eligibility

About

The primary objective of this study is to evaluate the safety and tolerability of single and multiple doses at escalating dose levels of mRNA-0184.

Full description

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.

Enrollment: 98 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: Single Blind

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98 participants in 3 patient groups, including a placebo group

SAD Stage: mRNA-0184

Experimental group

Description:

Participants will receive a single dose of mRNA-0184.

Treatment:

Drug: mRNA-0184

MAD Stage: mRNA-0184

Experimental group

Description:

Participants will receive up to 4 doses of mRNA-0184 administered over a treatment period of up to 16 weeks.

Treatment:

Drug: mRNA-0184

MAD Stage: Placebo

Placebo Comparator group

Description:

Participants will receive placebo matching to mRNA-0184 administered over a treatment period of up to 16 weeks.

Treatment:

Drug: Placebo