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

A Phase 1, Adaptive, Open-Label, Single Ascending Dose to Single-Blind, Placebo-Controlled, Multiple Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of mRNA-0184 in Participants With Chronic Heart Failure

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.

Study Overview

• Status: Completed
• Conditions: Chronic Heart Failure
• Intervention / Treatment: Drug: Placebo; Drug: mRNA-0184

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 48
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Dolnoslaskie
    • Wroclaw, Dolnoslaskie, Poland, 50-556
      • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
  • Podlaskie
    • Bialystok, Podlaskie, Poland, 15-276
      • Uniwersytecki Szpital Kliniczny W Bialymstoku
  • Slaskie
    • Katowice, Slaskie, Poland, 40-635
      • Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach
  • Wielkopolskie
    • Poznan, Wielkopolskie, Poland, 61-848
      • Uniwersytecki Szpital Kliniczny W Poznaniu
• United Kingdom
  • Liverpool, United Kingdom, L7 8XP
    • The Royal Liverpool University Hospital
  • Angus
    • Dundee, Angus, United Kingdom, DD1 9SY
      • Ninewells Hospital & Medical School
  • Cambridgeshire
    • Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ
      • Addenbrooke's Hospital
  • City Of London
    • London, City Of London, United Kingdom, NW1 2BU
      • University College Hospital
  • Devon
    • Plymouth, Devon, United Kingdom, PL6 8DH
      • Derriford Hospital
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Cardiology PC
    • Birmingham, Alabama, United States, 35233
      • University of Alabama at Birmingham: The Kirklin Clinic
  • Florida
    • Gainesville, Florida, United States, 32608
      • University of Florida
    • Jacksonville, Florida, United States, 32216
      • Jacksonville Center For Clinical Research - ERN - PPDS
  • Tennessee
    • Tullahoma, Tennessee, United States, 37388
      • Tennessee Center For Clinical Trials

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: SAD Stage: mRNA-0184; Participants will receive a single dose of mRNA-0184.	Drug: mRNA-0184; mRNA-0184 dispersion for intravenous (IV) infusion
Experimental: MAD Stage: mRNA-0184; Participants will receive up to 4 doses of mRNA-0184 administered over a treatment period of up to 16 weeks.	Drug: mRNA-0184; mRNA-0184 dispersion for intravenous (IV) infusion
Placebo Comparator: MAD Stage: Placebo; Participants will receive placebo matching to mRNA-0184 administered over a treatment period of up to 16 weeks.	Drug: Placebo; 0.9% sodium chloride (normal saline) injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	Baseline up to Day 296

Secondary Outcome Measures

Outcome Measure	Time Frame
Serum Concentrations of mRNA Encoding Relaxin-2-variable Light Chain Kappa (Rel2- vlk mRNA)	Day 1 (within 60 minutes predose) up to Day 183
Maximum Observed Plasma Concentration (Cmax) of Rel2-vlk mRNA	Day 1 (within 60 minutes predose) up to Day 183
Area Under the Curve From Time 0 to Time t (AUC0-t) of Rel2-vlk mRNA	Day 1 (within 60 minutes predose) up to Day 183
Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein	Day 1 (within 60 minutes predose) up to Day 183
Maximum Observed Effect (Emax) of Rel2- vlk Protein	Day 1 (within 60 minutes predose) up to Day 183
Number of Participants With Anti-polyethylene glycol (PEG) Antibodies	Baseline up to Day 183
Number of Participants With anti-Rel2-vlk Protein Antibodies	Baseline up to Day 183
Area Under the Effect-Time Curve (AUEC) of Rel2-vlk Protein	Day 1 (within 60 minutes predose) up to Day 183

Collaborators and Investigators

• Sponsor: ModernaTX, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 5, 2022
• Primary Completion (Actual): December 17, 2024
• Study Completion (Actual): December 17, 2024

Study Registration Dates

• First Submitted: December 13, 2022
• First Submitted That Met QC Criteria: December 13, 2022
• First Posted (Actual): December 21, 2022

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 14, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Multiple ascending dose; Single ascending dose; mRNA-0184
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: mRNA-0184-P101; 2022-000784-46 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No