A Study to Evaluate the Safety of mRNA-0184 in Participants With Heart Failure
- Registration Number
- NCT05659264
- Lead Sponsor
- ModernaTX, Inc.
- 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.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 48
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SAD Stage: mRNA-0184 mRNA-0184 Participants will receive a single dose of mRNA-0184. MAD Stage: mRNA-0184 mRNA-0184 Participants will receive up to 4 doses of mRNA-0184 administered over a treatment period of up to 16 weeks. MAD Stage: Placebo Placebo Participants will receive placebo matching to mRNA-0184 administered over a treatment period of up to 16 weeks.
- Primary Outcome Measures
Name Time Method Number of Participants With Treatment-Emergent Adverse Events (TEAEs) Baseline up to Day 296
- Secondary Outcome Measures
Name Time Method Serum Concentrations of Relaxin-2-variable Light Chain Kappa (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 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 Effect-Time Curve (AUEC) of Rel2-vlk Protein 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 Maximum Observed Effect (Emax) of Rel2- vlk Protein Day 1 (within 60 minutes predose) up to Day 183 Number of Participants With anti-Rel2-vlk Protein Antibodies Baseline up to Day 183
Trial Locations
- Locations (14)
Jacksonville Center For Clinical Research - ERN - PPDS
🇺🇸Jacksonville, Florida, United States
Tennessee Center for Clinical Trials
🇺🇸Tullahoma, Tennessee, United States
Uniwersytecki Szpital Kliniczny w Bialymstoku
🇵🇱Bialystok, Podlaskie, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Poznan, Wielkopolskie, Poland
Ninewells Hospital & Medical School
🇬🇧Dundee, Angus, United Kingdom
University of Florida
🇺🇸Gainesville, Florida, United States
Derriford Hospital
🇬🇧Plymouth, Devon, United Kingdom
Addenbrooke's Hospital
🇬🇧Cambridge, Cambridgeshire, United Kingdom
University College Hospital
🇬🇧London, City Of London, United Kingdom
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
🇵🇱Wroclaw, Dolnoslaskie, Poland
Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach
🇵🇱Katowice, Slaskie, Poland
Cardiology PC
🇺🇸Birmingham, Alabama, United States
University of Alabama at Birmingham: The Kirklin Clinic
🇺🇸Birmingham, Alabama, United States
The Royal Liverpool University Hospital
🇬🇧Liverpool, United Kingdom