A research study comparing CDR132L with placebo on the structure and function of the heart in people with heart failure with reduced/mildly reduced ejection fraction and left ventricular hypertrophy

Prior treatment

• Participants with an episode of acute kidney failure or acute kidney injury, at the discretion of the investigator, within 90 days prior to randomisation.
• Myocardial infarction, unstable angina pectoris or HF hospitalisation within 30 days prior to screening.
• Participants receiving intravenous HF medications within 45 days prior to randomisation.
• Stroke or transient ischemic attack within 12 months prior to randomisation.

Other illness

• Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis.
• Planned coronary revascularisation, pacemaker/cardioverter-defibrillator/CRT implantation, ablation of cardiac arrythmias or valve repair/replacement at the time of randomisation.
• Known genetic (or highly suspected due to family history) cause of increased cardiac mass (including dilated cardiomyopathy, Fabry disease and likely pathogenic or pathogenic variants within hypertrophic cardiomyopathy [HCM])).

Lab values

• eGFR <30 mL/min/1.73 m2 at time of screening, measured by central laboratory.
• Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase >2.5x upper limit of normal at screening, measured by central laboratory.

Other

• Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator.

• Age 40-84 years (both inclusive) at the time of signing the informed consent.
• Documented symptomatic HF diagnosed ≥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 ≥45 days prior to randomisation.
• LVEF <50% as assessed by echocardiography at screening, measured by central laboratory.
• Left ventricular hypertrophy or left ventricular dilatation assessed by echocardiography at screening measured by central laboratory with any of the following: a. LVMi >88 g/m2 for female participants and >102 g/m2 for male participants, using the truncated ellipsoid method. b. LVMi >95 g/m2 for female participants and >115 g/m2 for male participants, using the linear method (cube formula). c. Left ventricular end-diastolic diameter indexed to body surface area (LVEDDi) >3.1 cm/m2 for female participants and >3.0 cm/m2 for male participants.
• Body mass index 18.5-40 kg/m2 (both inclusive) and body weight ≤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 ≥300 pg/mL; NT-proBNP ≥600 pg/mL if atrial fibrillation/flutter is present at time of screening, measured by central laboratory.