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

Chronic Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05659264
• Other study ID #: mRNA-0184-P101
• Secondary ID: 2022-000784-46
• Status: Recruiting
• Phase: Phase 1
• Start date: December 5, 2022
• Est. completion date: March 6, 2025

Study information

• Verified date: February 2024
• Source: ModernaTX, Inc.
• Contact: Moderna Clinical Trials Support Center
• Phone: 1-877-777-7187
• Email: clinicaltrials[@]modernatx.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 98
• Est. completion date: March 6, 2025
• Est. primary completion date: March 6, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Heart Failure
• Heart Failure

Intervention

Drug:
• mRNA-0184
mRNA-0184 dispersion for intravenous (IV) infusion
• Placebo
0.9% sodium chloride (normal saline) injection

Locations

Country	Name	City	State
Poland	Uniwersytecki Szpital Kliniczny w Bialymstoku	Bialystok	Podlaskie
Poland	Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach	Katowice	Slaskie
Poland	Wojewodzki Specjalistyczny Szpital im Dr Wl Bieganskiego w Lodzi	Lódz	Lódzkie
Poland	Uniwersytecki Szpital Kliniczny w Opolu	Opole	Opolskie
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Poznan	Wielkopolskie
Poland	Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu	Wroclaw	Dolnoslaskie
United Kingdom	Addenbrooke's Hospital	Cambridge	Cambridgeshire
United Kingdom	Ninewells Hospital & Medical School	Dundee	Angus
United Kingdom	The Royal Liverpool University Hospital	Liverpool
United Kingdom	University College Hospital	London	City Of London
United Kingdom	Derriford Hospital	Plymouth	Devon
United States	Cardiology PC	Birmingham	Alabama
United States	University of Alabama at Birmingham: The Kirklin Clinic	Birmingham	Alabama
United States	University of Florida	Gainesville	Florida
United States	Jacksonville Center For Clinical Research - ERN - PPDS	Jacksonville	Florida
United States	Tennessee Center for Clinical Trials	Tullahoma	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
ModernaTX, Inc.

Countries where clinical trial is conducted

United States,  Poland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)		Baseline up to Day 296
Secondary	Serum Concentrations of mRNA Encoding Relaxin-2-variable Light Chain Kappa (Rel2- vlk mRNA)		Day 1 (within 60 minutes predose) up to Day 183
Secondary	Maximum Observed Plasma Concentration (Cmax) of Rel2-vlk mRNA		Day 1 (within 60 minutes predose) up to Day 183
Secondary	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
Secondary	Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein		Day 1 (within 60 minutes predose) up to Day 183
Secondary	Maximum Observed Effect (Emax) of Rel2- vlk Protein		Day 1 (within 60 minutes predose) up to Day 183
Secondary	Area Under the Effect-Time Curve (AUEC) of Rel2-vlk Protein		Day 1 (within 60 minutes predose) up to Day 183
Secondary	Number of Participants With Anti-polyethylene glycol (PEG) Antibodies		Baseline up to Day 183
Secondary	Number of Participants With anti-Rel2-vlk Protein Antibodies		Baseline up to Day 183