A Study to Evaluate the Safety of mRNA-0184 in Participants With Heart Failure
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
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 Design
Arms and Interventions
| 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
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs) [Baseline up to Day 296]
Secondary Outcome Measures
- 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]
- Area Under the Effect-Time Curve (AUEC) of Rel2-vlk mRNA [Day 1 (within 60 minutes predose) up to Day 183]
- Stroke Volume (SV) [Baseline up to Day 183]
- Cardiac Output (CO) [Baseline up to Day 183]
- Cardiac Index (CI) [Baseline 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]
Eligibility Criteria
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.
-
Symptoms of angina pectoris at Screening.
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Severe obstructive or restrictive pulmonary pathology, including chronic obstructive pulmonary disease Gold Stage III or IV, current use of oxygen therapy, or pulmonary hypertension.
-
History of sustained ventricular tachycardia or atrial fibrillation/atrial flutter with a ventricular response ≥ 110 beats per minute (bpm) at the time of Screening.
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History of hypersensitivity to any components of the investigational product (IP).
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Participant has received a COVID-19 vaccination (irrespective of type of vaccine) or is anticipated to require a second dose of a 2-dose COVID-19 vaccine series within 7 days of the planned date of IP administration.
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For SAD cohort participants to be rolled over into the MAD stage, have experienced a dose-limiting toxicity (DLT) in a SAD cohort.
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Participation in another clinical study of another IP within 30 days before Screening or within 5 effective elimination half-lives of the IP, whichever is longer.
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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.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu | Wroclaw | Dolnoslaskie | Poland | 50-556 |
| 2 | Wojewodzki Specjalistyczny Szpital im Dr Wl Bieganskiego w Lodzi | Lódz | Lódzkie | Poland | 91-347 |
| 3 | Uniwersytecki Szpital Kliniczny w Bialymstoku | Bialystok | Podlaskie | Poland | 15-276 |
| 4 | Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach | Katowice | Slaskie | Poland | 40-635 |
| 5 | Ninewells Hospital & Medical School | Dundee | Angus | United Kingdom | DD1 |
| 6 | Derriford Hospital | Plymouth | Devon | United Kingdom | PL6 8DH |
Sponsors and Collaborators
- ModernaTX, Inc.
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- mRNA-0184-P101