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

Primary Purpose

Chronic Heart Failure

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
mRNA-0184
Placebo
Sponsored by
ModernaTX, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Heart Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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. 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.

Sites / Locations

  • Cardiology PC
  • University of Alabama at Birmingham: The Kirklin Clinic
  • University of Florida
  • Jacksonville Center For Clinical Research - ERN - PPDS
  • Tennessee Center for Clinical Trials
  • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we WroclawiuRecruiting
  • Wojewodzki Specjalistyczny Szpital im Dr Wl Bieganskiego w Lodzi
  • Uniwersytecki Szpital Kliniczny w BialymstokuRecruiting
  • Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w KatowicachRecruiting
  • Uniwersytecki Szpital Kliniczny w Poznaniu
  • Ninewells Hospital & Medical SchoolRecruiting
  • Addenbrooke's HospitalRecruiting
  • University College HospitalRecruiting
  • Derriford Hospital
  • The Royal Liverpool University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

SAD Stage: mRNA-0184

MAD Stage: mRNA-0184

MAD Stage: Placebo

Arm Description

Participants will receive a single dose of mRNA-0184.

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Serum Concentrations of mRNA Encoding Relaxin-2-variable Light Chain Kappa (Rel2- vlk mRNA)
Maximum Observed Plasma Concentration (Cmax) of Rel2-vlk mRNA
Area Under the Curve From Time 0 to Time t (AUC0-t) of Rel2-vlk mRNA
Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein
Maximum Observed Effect (Emax) of Rel2- vlk Protein
Area Under the Effect-Time Curve (AUEC) of Rel2-vlk mRNA
Number of Participants With Anti-polyethylene glycol (PEG) Antibodies
Number of Participants With anti-Rel2-vlk Protein Antibodies

Full Information

First Posted
December 13, 2022
Last Updated
September 29, 2023
Sponsor
ModernaTX, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05659264
Brief Title
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

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
November 18, 2022 (Actual)
Primary Completion Date
May 7, 2024 (Anticipated)
Study Completion Date
May 7, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
ModernaTX, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
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.
Masking
Participant
Allocation
Randomized
Enrollment
98 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
SAD Stage: mRNA-0184
Arm Type
Experimental
Arm Description
Participants will receive a single dose of mRNA-0184.
Arm Title
MAD Stage: mRNA-0184
Arm Type
Experimental
Arm Description
Participants will receive up to 4 doses of mRNA-0184 administered over a treatment period of up to 16 weeks.
Arm Title
MAD Stage: Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo matching to mRNA-0184 administered over a treatment period of up to 16 weeks.
Intervention Type
Drug
Intervention Name(s)
mRNA-0184
Intervention Description
mRNA-0184 dispersion for intravenous (IV) infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
0.9% sodium chloride (normal saline) injection
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
Time Frame
Baseline up to Day 296
Secondary Outcome Measure Information:
Title
Serum Concentrations of mRNA Encoding Relaxin-2-variable Light Chain Kappa (Rel2- vlk mRNA)
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Maximum Observed Plasma Concentration (Cmax) of Rel2-vlk mRNA
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Area Under the Curve From Time 0 to Time t (AUC0-t) of Rel2-vlk mRNA
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Maximum Observed Effect (Emax) of Rel2- vlk Protein
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Area Under the Effect-Time Curve (AUEC) of Rel2-vlk mRNA
Time Frame
Day 1 (within 60 minutes predose) up to Day 183
Title
Number of Participants With Anti-polyethylene glycol (PEG) Antibodies
Time Frame
Baseline up to Day 183
Title
Number of Participants With anti-Rel2-vlk Protein Antibodies
Time Frame
Baseline up to Day 183

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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. 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Moderna Clinical Trials Support Center
Phone
1-877-777-7187
Email
clinicaltrials@modernatx.com
Facility Information:
Facility Name
Cardiology PC
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35211
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Alabama at Birmingham: The Kirklin Clinic
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Florida
City
Gainesville
State/Province
Florida
ZIP/Postal Code
32608
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Jacksonville Center For Clinical Research - ERN - PPDS
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32216
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Tennessee Center for Clinical Trials
City
Tullahoma
State/Province
Tennessee
ZIP/Postal Code
37388
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wroclawiu
City
Wroclaw
State/Province
Dolnoslaskie
ZIP/Postal Code
50-556
Country
Poland
Individual Site Status
Recruiting
Facility Name
Wojewodzki Specjalistyczny Szpital im Dr Wl Bieganskiego w Lodzi
City
Lódz
State/Province
Lódzkie
ZIP/Postal Code
91-347
Country
Poland
Individual Site Status
Not yet recruiting
Facility Name
Uniwersytecki Szpital Kliniczny w Bialymstoku
City
Bialystok
State/Province
Podlaskie
ZIP/Postal Code
15-276
Country
Poland
Individual Site Status
Recruiting
Facility Name
Gornoslaskie Centrum Medyczne im. prof. Leszka Gieca Slasiego Uniwersytetu Medycznego w Katowicach
City
Katowice
State/Province
Slaskie
ZIP/Postal Code
40-635
Country
Poland
Individual Site Status
Recruiting
Facility Name
Uniwersytecki Szpital Kliniczny w Poznaniu
City
Poznan
State/Province
Wielkopolskie
ZIP/Postal Code
61-848
Country
Poland
Individual Site Status
Not yet recruiting
Facility Name
Ninewells Hospital & Medical School
City
Dundee
State/Province
Angus
ZIP/Postal Code
DD1
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Addenbrooke's Hospital
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB20QQ
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
University College Hospital
City
London
State/Province
City Of London
ZIP/Postal Code
NW1 2BU
Country
United Kingdom
Individual Site Status
Recruiting
Facility Name
Derriford Hospital
City
Plymouth
State/Province
Devon
ZIP/Postal Code
PL6 8DH
Country
United Kingdom
Individual Site Status
Not yet recruiting
Facility Name
The Royal Liverpool University Hospital
City
Liverpool
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Individual Site Status
Recruiting

12. IPD Sharing Statement

Learn more about this trial

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

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