NCT05659264已完成1 期
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
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 48
- 试验地点
- 14
- 主要终点
- Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
研究组 & 干预措施
SAD Stage: mRNA-0184
Experimental
Participants will receive a single dose of mRNA-0184.
干预措施: mRNA-0184 (Drug)
MAD Stage: mRNA-0184
Experimental
Participants will receive up to 4 doses of mRNA-0184 administered over a treatment period of up to 16 weeks.
干预措施: mRNA-0184 (Drug)
MAD Stage: Placebo
Placebo Comparator
Participants will receive placebo matching to mRNA-0184 administered over a treatment period of up to 16 weeks.
干预措施: Placebo (Drug)
结局指标
主要结局
Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
时间窗: Baseline up to Day 296
次要结局
- Serum Concentrations of Relaxin-2-variable Light Chain Kappa (Rel2- vlk) Protein(Day 1 (within 60 minutes predose) up to Day 183)
- Number of Participants With Anti-polyethylene glycol (PEG) Antibodies(Baseline up to Day 183)
- 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 Effect-Time Curve (AUEC) of Rel2-vlk Protein(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)
- Maximum Observed Effect (Emax) of Rel2- vlk Protein(Day 1 (within 60 minutes predose) up to Day 183)
- Number of Participants With anti-Rel2-vlk Protein Antibodies(Baseline up to Day 183)
研究者
研究点 (14)
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