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

NCT05659264 | Completed Phase 1 DMC FDA Drug

• 2 other identifiers: mRNA-0184-P1012022-000784-46
• Study Type: interventional
• Target: 48
• Locations: 3 countries
• Sites: 14

Brief Summary

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.

Conditions

Chronic Heart Failure

Keywords

Single ascending dose; Multiple ascending dose; mRNA-0184; Heart failure

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

  Baseline up to Day 296

Secondary Outcomes (8)

• 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

Study Arms (3)

SAD Stage: mRNA-0184

EXPERIMENTAL

Participants will receive a single dose of mRNA-0184.

Drug: mRNA-0184

MAD Stage: mRNA-0184

EXPERIMENTAL

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

Drug: mRNA-0184

MAD Stage: Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

mRNA-0184 DRUG

mRNA-0184 dispersion for intravenous (IV) infusion

MAD Stage: mRNA-0184; SAD Stage: mRNA-0184

Placebo DRUG

0.9% sodium chloride (normal saline) injection

MAD Stage: Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Hospitalized for cardiovascular causes within 3 months before Screening.
• Symptoms of angina pectoris at Screening.
• 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.

Sponsors & Collaborators

• ModernaTX, Inc.: lead

Study Sites (14)

Cardiology PC

Birmingham, Alabama, 35211, United States

Location

University of Alabama at Birmingham: The Kirklin Clinic

Birmingham, Alabama, 35233, United States

Location

University of Florida

Gainesville, Florida, 32608, United States

Location

Jacksonville Center For Clinical Research - ERN - PPDS

Jacksonville, Florida, 32216, United States

Location

Tennessee Center for Clinical Trials

Tullahoma, Tennessee, 37388, United States

Location

Uniwersytecki Szpital Kliniczny w Poznaniu

Poznan, Greater Poland Voivodeship, 61-848, Poland

Location

Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu

Wroclaw, Lower Silesian Voivodeship, 50-556, Poland

Location

Uniwersytecki Szpital Kliniczny w Bialymstoku

Bialystok, Podlaskie Voivodeship, 15-276, Poland

Location

Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach

Katowice, Silesian Voivodeship, 40-635, Poland

Location

Ninewells Hospital & Medical School

Dundee, Angus, DD1 9SY, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, Cambridgeshire, CB2 0QQ, United Kingdom

Location

University College Hospital

London, City of London, NW1 2BU, United Kingdom

Location

Derriford Hospital

Plymouth, Devon, PL6 8DH, United Kingdom

Location

The Royal Liverpool University Hospital

Liverpool, L7 8XP, United Kingdom

Location

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: The single ascending dose (SAD) stage of this study is open-label and the multiple ascending dose (MAD) stage of this study is single-blind and placebo-controlled.

Study Record Dates

• First Submitted: December 13, 2022
• First Posted: December 21, 2022
• Study Start: December 5, 2022
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: March 17, 2025

Record last verified: 2025-03

Locations

GB (5); US (5); PL (4)