A Research Study Comparing Different Doses of CDR132L With Placebo on the Structure and Function of the Heart in People With Heart Failure With Preserved Ejection Fraction and Left Ventricular Hypertrophy

Official title

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

Overview

This study will look into how CDR132L (a potential new medicine) works on the structure and function of the heart in people living with heart failure. Participants will either get CDR132L or placebo (a medicine which has no effect on the body), which treatment the participants get is decided by chance. The study will last for about 60 weeks.

Interventions

• Drug CDR132L
  CDR132L will be administered intravenously once every 4 weeks.
• Drug Placebo
  Placebo will be administered intravenously once every 4 weeks.

Primary outcome measures

• Main phase: Change in normalised microRNA-132-3p (miR-132) [Time frame: From baseline to week 24]

Secondary outcome measures (4)

• Main phase: Change in composite Z-score based on the 3 outcome measures LVMi (CMR), LAVi (CMR) and NT-proBNP [Time frame: From baseline to week 24]
• Main phase: Change in normalised miR-132 [Time frame: From baseline to week 24]
• Main phase: Number of adverse events [Time frame: From baseline to week 24]
• Extension phase: Number of adverse events [Time frame: From baseline to week 60]

Eligibility criteria

Inclusion criteria

• Age 40-84 years (both inclusive) at the time of signing the informed consent
• Documented symptomatic chronic heart failure (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
• Clinically stable and on optimised doses and unchanged drug classes of guideline-directed HF therapy ≥45 days prior to randomisation
• Left ventricular ejection fraction ≥50% as assessed by echocardiography at screening, measured by central laboratory
• Left ventricular hypertrophy assessed by echocardiography at screening measured by central laboratory with any of the following:

• LVMi (greater than) >88 gram per square meter (g/m\^2) for female participants and >102 g/m\^2 for male participants, using the truncated ellipsoid method measured by central laboratory
• LVMi >95 g/m2 for female participants and >115 g/m2 for male participants using the linear method (cube formula).
• Interventricular septum diameter measured in diastole (IVSd) in the parasternal long axis view ≥1.1 cm for female participants and ≥1.2 cm for male participants.
• Body mass index 18.5-40 kilogram per square meter (kg/m\^2) (both inclusive) and body weight less than or equal to (≤) 140 kilogram (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 picograms per milliliter (pg/mL); NT-proBNP ≥600 pg/mL if atrial fibrillation/flutter is present at time of screening, measured by central laboratory

Exclusion criteria

• Estimated glomerular filtration rate lesser than (<) 30 milliliter per minute (mL/min)/1.73 square meter (m\^2) at time of screening, measured by central laboratory
• 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
• Participants with CRT, pacemaker or implantable cardioverter-defibrillator
• Planned coronary revascularisation, pacemaker/cardioverter-defibrillator/CRT implantation, ablation of cardiac arrythmias and valve repair/replacement at the time of randomisation
• Stroke or transient ischemic attack within 12 months prior to randomisation
• Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator
• Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase >2.5 x upper limit of normal at screening, measured by central laboratory
• 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 \[HCM\]).
• Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 29 centers

• Univ of Alabama Birmingham — Birmingham
• TMC Hlthcr Clin Res Office — Tucson
• Pima Heart and Vascular — Tucson
• Valley Clinical Trials — Covina
• UCSD NAFLD Research Center — La Jolla
• Valley Clinical Trials — Northridge
• University of California, San Francisco — San Francisco
• University of California San Francisco UCSF — San Francisco
• … and 21 more centers

India · 15 centers

• Rhythm Heart Institute - A unit of Synergy Lifecare Pvt — Vadodara
• Sengupta Hospital and Research Institute — Nagpur
• All India Institute of Medical Sciences (AIIMS), Nagpur — Nagpur
• All India Institute of Medical Sciences (AIIMS), Nagpur — Nagpur
• G B Pant Institute of Postgraduate Medical Education and Research — New Delhi
• VMMC & Safdarjung Hospital — New Dehli
• VMMC & Safdarjung Hospital — New Dehli
• Government Siddhartha Medical College & Government General Hospital, Vijayawada — Vijayawada
• … and 7 more centers

Poland · 14 centers

• 4 Wojskowy Szpital Kliniczny Z Poliklinika Samodzielny Publiczny Zaklad Opieki Zdrowotnej — Wroclaw
• … and 13 more centers

Japan · 13 centers

• NIPPON MEDICAL SCHOOL HOSPITAL_Cardiovascular medicine — Bunkyo-ku, Tokyo
• Hyogo Prefectural HarimaHimeji General Medical Center_Cardiology — Himeji-shi, Hyogo
• National Hospital Organization Mito Medical Center_Cardiovascular medicine — Ibaraki
• Mitoyo General Hospital_Cardiovascular medicine — Kagawa
• Yokohama City University Medical Center_Cardiovascular Center — Kanagawa
• Yokohama City University Medical Center_Cardiovascular Center — Kanagawa
• Kagawa University Hospital_Cardiology — Kita-gun, Kagawa
• Kobe City Medical Center General Hospital_Cardiology — Kobe-shi, Hyogo
• … and 5 more centers

Canada · 12 centers

• St Pauls Hospital — Vancouver
• William Osler Hel Bra Civic Hs — Brampton
• Hamilton Hlth Sc. - General Site — Hamilton
• Hamilton General Hospital — Hamilton
• Premier Clinical Trial Research Network (PCTRN) — Hamilton
• Cardio Health Clinical Trials — Hamilton
• Cardio Health Clinical Trials — Mississauga
• University of Ottawa Heart Institute (UOHI) — Ottawa
• … and 4 more centers

Germany · 10 centers

• Sana Kliniken Berlin-Brandenburg GmbH - Lichtenberg — Berlin
• Charité - Campus Benjamin Franklin - Klinik für Kardiologie — Berlin
• Charité - Campus Virchow-Klinikum - Kardiologie, Angiologie und Intensivmedizin (CRU) — Berlin
• Uniklinik TU Dresden - Herzzentrum Dresden GmbH — Dresden
• Universitaetsklinikum Essen - Klinik für Kardiologie und Angiologie — Essen
• Universitätsklinikum Frankfurt aM - Kardiologie — Frankfurt am Main
• Universitätsklinikum Halle - Innere Medizin III — Halle
• Medizinische Hochschule Hannover - Kardiologie und Angiologie — Hanover
• … and 2 more centers

South Korea · 8 centers

Center list to be confirmed — check the primary protocol.

Spain · 8 centers

Center list to be confirmed — check the primary protocol.

United Kingdom · 8 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06979362 · NN6706-8212 · U1111-1313-3984 · 2024-515796-35 · jRCT2031250304

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗