Phase I study to evaluate the safety of mRNA-0184 in participants with heart failure

Phase 1

• Conditions: Chronic heart failure; Circulatory System; Heart failure

• Registration Number: ISRCTN79552451
• Lead Sponsor: Moderna France

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2022-10-21
• Last Update Posted: 14 November 2022
• Study Completion: 2024-07-04

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 98

Inclusion Criteria

1. Age =18 years at the time of informed consent
2. Documented diagnosis of HF based on medical records
3. Left ventricular ejection fraction (LVEF) =35% and <50% at Screening, or documented within the 3 months before Screening, measured by TTE or cardiac magnetic resonance imaging (MRI)
4. New York Heart Association (NYHA) HF Class I or II
5. On a stable regimen of cardiovascular medication(s) for a duration of at least 4 weeks before Screening
6. Heart rate =50 bpm at Screening
7. Systolic blood pressure =110 mmHg and =160 mmHg at Screening
8. Sexually active female participants of childbearing potential and sexually active male participants of reproductive potential agree to use a highly effective method of contraception during the study and for 6 months after the last administration of IP

Exclusion Criteria

1. Hospitalized for cardiovascular causes within 3 months before Screening
2. 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
3. Symptoms of angina pectoris at Screening
4. Severe obstructive or restrictive pulmonary pathology, including chronic obstructive pulmonary disease Gold Stage III or IV current use of oxygen therapy, or pulmonary hypertension
5. History of sustained ventricular tachycardia or atrial fibrillation/atrial flutter with a ventricular response =110 bpm at the time of Screening
6. Severe renal impairment defined as one or both of the following:
6.1. Estimated glomerular filtration rate (eGFR) <30 ml/min/1.73 m², calculated using the Simplified Modification of Diet in Renal Disease equation
6.2. Current or planned dialysis or ultrafiltration
7. Prolonged QTcF >450 ms at Screening
8. Laboratory abnormality within an exclusionary threshold at Screening
9. For female participants, positive pregnancy test at Screening or Baseline or currently breastfeeding
10. Hypersensitivity to acetaminophen/paracetamol or H1-receptor or H2-receptor blockers
11. History of hypersensitivity to any components of the IP
12. Active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), hepatitis B (known positive hepatitis B surface antigen [HBsAg] result), hepatitis C virus (HCV), or HIV (positive HIV-1/HIV-2 antibodies). Participants with a past or resolved hepatitis virus B (HBV) infection(defined as the presence of hepatitis B core antibody and absence of HBsAg) are eligible. Participants positive for HCV antibody are eligible only if polymerase chain reaction is negative for HCV ribonucleic acids (RNA)
13. Participant has received a COVID-19 vaccination (irrespective of type of vaccine) or is anticipated to require a second dose of a two-dose COVID-19 vaccine series within 7 days of the planned date of IP administration
14. For SAD cohort participants to be rolled over into the MAD stage, have experienced a DLT in a SAD cohort
15. 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
16. Has a positive urine drug screen for any of the following nonprescription drugs of abuse at Screening: alcohol, opiates, cocaine, phencyclidine, amphetamines, methamphetamines, barbiturates, benzodiazepines, or methadone. Positive drug screens for benzodiazepines or opiates will not be exclusionary if prescribed concomitant medications can justify the result
17. 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

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<br> 1. Incidence and severity of TEAEs, SAEs, and TEAEs leading to treatment discontinuation. This is measured at 26 weeks for the SAD stage, 8 weeks for the MAD stage Q2W, 12 weeks for the MAD stage Q3W and 16 weeks for the MAD stage Q4W.<br> 2. Vital signs, weight, physical examination findings, ECG results, and laboratory findings (including hematology, serum chemistry, urinalysis, and coagulation parameters). This is measured at 26 weeks for the SAD stage, 8 weeks for the MAD stage Q2W, 12 weeks for the MAD stage Q3W and 16 weeks for the MAD stage Q4W.<br>