Phase 2, Multicentre, Randomised, Double-blind, Placebo-controlled Safety and Efficacy Study of CDR132L on Reverse Cardiac Remodelling in Participants with Heart Failure with Reduced/Mildly Reduced Ejection Fraction and Left Ventricular Hypertrophy
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- Novo Nordisk
- 入组人数
- 200
- 试验地点
- 9
- 主要终点
- To confirm superiority of 4.52 mg/kg CDR132L Q4W versus placebo Q4W, both added to standard of care, on change in miR-132 from baseline to week 24 in participants with HFrEF/HFmrEF and LVH.
研究概览
简要总结
Synopsis
This is an interventional, multinational, multicentre, randomised, parallel, double-blind,
placebo-controlled study.
Rationale:
The overall purpose of this phase 2 study is to investigate the efficacy and safety of CDR132L in
adult participants with heart failure (HF) with mildly reduced ejection fraction (HFmrEF) and
reduced ejection fraction (HFrEF), i.e., left ventricular ejection fraction (LVEF) less than 50%, 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:
The efficacy of CDR132L on suppression of plasma microRNA-132-3p (miR-132) levels
The efficacy of CDR132L on inducing cardiac reverse remodelling over a 24-week period as
evaluated by a 3-item Z-score composed of left ventricular end-diastolic volume indexed to
body surface area (LVEDVi), left ventricular end-systolic volume indexed to body surface
area (LVESVi) and N-terminal pro B-type natriuretic peptide (NT-proBNP).
The extension phase is designed to investigate:
The efficacy of CDR132L on suppression of plasma miR-132 levels and on inducing cardiac
reverse remodelling as evaluated by the 3-item Z-score after 48 weeks of treatment.
The main phase and extension phase, including the follow-up period, will provide data on safety,
including renal safety in participants with estimated glomerular filtration rate (eGFR) down to
30 mL per min per 1.73 m2, to support selection of the study population for phase 3.
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 85.00 Year(s)（—）
- 性别
- All
入选标准
- •Age 40-84 years (both inclusive) at the time of signing the informed consent.
- •Documented symptomatic HF diagnosed greater than or equal to 180 days prior to screening with at least weekly need for oral diuretic treatment, and New York Heart Association class II−III at screening.
- •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.
- •LVEF lesser than 50 percentage as assessed by echocardiography at screening, measured by central laboratory.
- •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.
- •LAVi greater than or equal to 29 mL per m2 as assessed by echocardiography at screening, measured by central laboratory.
- •Body mass index 18.5-40 kg per m2 (both inclusive) and body weight lesser 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).
- •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
- •1.eGFR 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.Planned coronary revascularisation, pacemaker/cardioverter-defibrillator/CRT implantation, ablation of cardiac arrythmias or valve repair/replacement at the time of randomisation.
- •6.Stroke or transient ischemic attack within 12 months prior to randomisation.
- •7.Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator 8.Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase greater than 2.5x upper limit of normal at screening, measured by central laboratory 9.Known genetic cause of increased cardiac mass (including likely pathogenic variants within dilated cardiomyopathy, hypertrophic cardiomyopathy and Fabry disease).
- •10.Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis.
结局指标
主要结局
To confirm superiority of 4.52 mg/kg CDR132L Q4W versus placebo Q4W, both added to standard of care, on change in miR-132 from baseline to week 24 in participants with HFrEF/HFmrEF and LVH.
时间窗: From baseline (V2) to | week 24 (V14)
Change in miR-132
时间窗: From baseline (V2) to | week 24 (V14)
次要结局
- Main Phase:(1. To compare the effect of 4.52 mg/kg CDR132L Q4W versus placebo Q4W on the composite Z-score based on the 3 outcome measures LVEDVi, LVESVi and NT-proBNP.)