Clinical trial NCT05659264: A Study to Evaluate the Safety of mRNA-0184 in Participants With Heart Failure
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Chronic Heart Failure
Keywords: Single ascending dose
Multiple ascending dose
mRNA-0184
Heart failure
Lead sponsor: ModernaTX, Inc.
Sponsor class: INDUSTRY
First posted: 2022-12-21
Enrollment: 48
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: 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.
Primary purpose: TREATMENT

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.

Eligibility 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. 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.

Primary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
timeFrame: Baseline up to Day 296
Secondary outcomes:
measure: Serum Concentrations of mRNA Encoding Relaxin-2-variable Light Chain Kappa (Rel2- vlk mRNA)
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Maximum Observed Plasma Concentration (Cmax) of Rel2-vlk mRNA
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Area Under the Curve From Time 0 to Time t (AUC0-t) of Rel2-vlk mRNA
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Maximum Observed Effect (Emax) of Rel2- vlk Protein
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Area Under the Effect-Time Curve (AUEC) of Rel2-vlk Protein
timeFrame: Day 1 (within 60 minutes predose) up to Day 183
measure: Number of Participants With Anti-polyethylene glycol (PEG) Antibodies
timeFrame: Baseline up to Day 183
measure: Number of Participants With anti-Rel2-vlk Protein Antibodies
timeFrame: Baseline up to Day 183
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama at Birmingham: The Kirklin Clinic
state: Alabama
city: Gainesville
country: United States
facility: University of Florida
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center For Clinical Research - ERN - PPDS
state: Florida
city: Tullahoma
country: United States
facility: Tennessee Center for Clinical Trials
state: Tennessee
city: Wroclaw
country: Poland
facility: Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
state: Dolnoslaskie
city: Bialystok
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Bialymstoku
state: Podlaskie
city: Katowice
country: Poland
facility: Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach
state: Slaskie
city: Poznan
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
state: Wielkopolskie
city: Dundee
country: United Kingdom
facility: Ninewells Hospital & Medical School
state: Angus
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
state: Cambridgeshire
city: London
country: United Kingdom
facility: University College Hospital
state: City Of London
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
state: Devon
city: Liverpool
country: United Kingdom
facility: The Royal Liverpool University Hospital
Study officials:
References: