Phase 2, Multicentre, Randomised, Double-blind, Placebo-controlled Safety and Efficacy Study of CDR132L on Reverse Cardiac Remodelling in Participants with Heart Failure with Preserved Ejection Fraction and Left Ventricular Hypertrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 10
- 主要终点
- Change in miR-132
研究概览
简要总结
This is an interventional multinational, multicentre, randomised, parallel, double-blind, placebo-controlled study.
The overall purpose of the present phase 2 study is to investigate the efficacy and safety of CDR132L in adult participants with heart failure with preserved ejection fraction (HFpEF) and left ventricular hypertrophy (LVH), as an add-on to standard of care (SoC) therapy.
The study comprises a 48-week treatment period consisting of a 24-week main phase followed by a 24-week extension phase, and a 12-week follow-up period.
The main phase is designed to investigate:
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the efficacy of CDR132L on suppression of plasma microRNA-132-3p (miR-132) levels
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which dose of CDR132L is optimal for reducing plasma levels of miR-132 in this patient population.
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the efficacy of CDR132L on inducing cardiac reverse remodelling over a 24-week period as evaluated on a 3-item Z-score composed of left ventricular mass indexed to body surface area (LVMi), left atrial volume indexed to body surface area (LAVi) and N-terminal pro B-type natriuretic peptide (NT-proBNP).
The extension phase is designed to investigate:
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whether effects on plasma miR-132 levels and 3-item Z-score are observed between weeks 24 and 48 in participants continuing treatment with CDR132L versus changing to placebo in the extension phase
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if maintenance dosing is needed, and what dose and frequency are required to maintain effects.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 盲法
- Participant and Investigator Blinded
入排标准
- 年龄范围
- 40.00 Year(s) 至 84.00 Year(s)（—）
- 性别
- All
入选标准
- •1.Age 40-84 years (both inclusive) at the time of signing the informed consent.
- •2.Documented symptomatic HF diagnosed greater than or equal to 90 days prior to screening with at least weekly need for oral diuretic treatment, and New York Heart Association class II−III at screening.
- •3.Clinically stable and on optimised doses and unchanged drug classes of guideline-directed HF therapy greater than or equal to 30 days prior to randomisation.
- •4.Left ventricular ejection fraction greater than or equal to 50% as assessed by echocardiography at screening, measured by central laboratory.
- •5.LVMi greater than 88 g per m2 for female participants and greater than 102 g per m2 for male participants as assessed by echocardiography at screening, using the truncated ellipsoid method measured by central laboratory.
- •6.LAVi greater than or equal to 29 mL per m2 as assessed by echocardiography at screening, measured by central laboratory.
- •7.Body mass index 18.5-40 kg per m2 (both inclusive) and body weight less than or equal to 140 kg.
- •Body mass index is calculated in the electronic case report form based on height and body weight at the screening visit (visit 1).
- •8.NT-proBNP greater than or equal to 300 pg per mL; NT-proBNP greater than or equal to 600 pg per mL if atrial fibrillation or flutter is present at time of screening, measured by central laboratory.
排除标准
- •Estimated glomerular filtration rate less than 30 mL per min per 1.73 m2 at time of screening, measured by central laboratory.
- •2.Participants with an episode of acute kidney failure or acute kidney injury, at the discretion of the investigator, within 90 days prior to randomisation.
- •3.Myocardial infarction, unstable angina pectoris or HF hospitalisation within 30 days prior to screening.
- •4.Participants receiving intravenous HF medications within 30 days prior to randomisation.
- •5.Participants with CRT, pacemaker or implantable cardioverter-defibrillator.
- •6.Planned coronary revascularisation, pacemaker or cardioverter-defibrillator or CRT implantation, ablation of cardiac arrythmias and valve repair or replacement at the time of randomisation.
- •7.Stroke or transient ischemic attack within 12 months prior to randomisation.
- •8.Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator.
- •9.Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase greater than 2.5 x upper limit of normal at screening, measured by central laboratory.
- •10.Known genetic cause of increased cardiac mass (including likely pathogenic variants within dilated cardiomyopathy, hypertrophic cardiomyopathy and Fabry disease).
- •Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis.
结局指标
主要结局
Change in miR-132
时间窗: From baseline (V2) to | week 24 (V14)
次要结局
- Supportive secondary efficacy:(Change in composite Z-score based on the 3 outcome measures LVMi(CMR),LAVi (CMR))