"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."

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Novo Nordisk A/S

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Cardiovascular Diseases [C14]

Trial duration

26 Jun 2025 → ongoing

Decision date (initial)

2025-05-28

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Novo Nordisk A/S

External identifiers

EU CT number

2024-515796-35-00

WHO UTN

U1111-1313-3984

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacokinetic, Therapy, Safety, Pharmacodynamic, Efficacy, Dose response

To confirm superiority of 00 mg/kg CDR132L Q4W versus placebo Q4W, both added to standard of care, on change in normalised miR-132 from baseline to week 24 in participants with HFpEF and LVH.

Secondary objectives 4

1. To compare the effect of 3 dose levels of CDR132L Q4W (00, 00, 00 mg/kg) versus placebo Q4W on the composite Z-score based on the 3 outcome measures LVMi (CMR), LAVi (CMR) and NTproBNP.
2. To compare the effect of 2 lower dose levels of CDR132L Q4W (00, 00 mg/kg) versus placebo Q4W on normalised miR-132.
3. To compare the effect of 3 dose levels of CDR132L Q4W (00, 00, 00 mg/kg) versus placebo Q4W on safety and tolerability.
4. To compare the effect of 3 dose levels of CDR132L Q4W (00, 00, 00 mg/kg) versus placebo Q4W regardless of re-randomisation at week 24 on safety and tolerability.

Conditions and MedDRA coding

Heart Failure with Preserved Ejection Fraction and Left Ventricular Hypertrophy.

Regulatory references

Scientific advice from competent authorities

Food And Drug Administration

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. 1. Age 40-84 years (both inclusive) at the time of signing the informed consent.
2. 2. Documented symptomatic HF diagnosed ≥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. 3. Clinically stable and on optimised doses and unchanged drug classes of guideline-directed HF therapy ≥45 days prior to randomisation.
4. 4. Left ventricular ejection fraction ≥50% as assessed by echocardiography at screening, measured by central laboratory.
5. 5. Left ventricular hypertrophy 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. 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.
6. 7. 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).
7. 8. NT-proBNP ≥300 pg/mL; NT-proBNP ≥600 pg/mL if atrial fibrillation/flutter is present at time of screening, measured by central laboratory.

Exclusion criteria 11

1. 1. Estimated glomerular filtration rate <30 mL/min/1.73 m2 at time of screening, measured by central laboratory.
2. 10. 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]).
3. 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.
4. 3. Myocardial infarction, unstable angina pectoris or HF hospitalisation within 30 days prior to screening.
5. 4. Participants receiving intravenous HF medications within 45 days prior to randomisation.
6. 5. Participants with CRT, pacemaker or implantable cardioverter-defibrillator.
7. 6. Planned coronary revascularisation, pacemaker/cardioverter-defibrillator/CRT implantation, ablation of cardiac arrythmias and valve repair/replacement at the time of randomisation.
8. 7. Stroke or transient ischemic attack within 12 months prior to randomisation.
9. 8. Participants with potential disruption of the blood-brain barrier (e.g., multiple sclerosis), in the opinion of the investigator.
10. 9. Known history of severe liver disease and/or alanine aminotransferase or aspartate aminotransferase >2.5× upper limit of normal at screening, measured by central laboratory.
11. 11. Participants with suspected or diagnosed cardiac amyloidosis or sarcoidosis

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Change in normalised miR-132 from baseline (V2) to week 24 (V14). Unit:  Ratio to baseline

Secondary endpoints 4

1. Change in composite Z-score based on the 3 outcome measures LVMi (CMR), LAVi (CMR) and NT-proBNP from baseline (V2) to week 24 (V14). Unit: Score
2. Change in normalised miR-132 from baseline (V2) to week 24 (V14). Unit: Ratio to baseline
3. Number of adverse events from baseline (V2) to week 24 (V14). Unit: Count
4. Number of adverse events From baseline (V2) to week 60 (V27). Unit: Count

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Novo Nordisk A/S

Sponsor organisation

Novo Nordisk A/S

Address

Novo Alle 1

City

Bagsvaerd

Postcode

2880

Country

Denmark

Scientific contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Public contact point

Organisation

Novo Nordisk A/S

Contact name

EU Submission Hub

Third parties 14

Locations

3 EU/EEA countries · 30 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 44 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

7 submissions — initial application plus substantial / non-substantial modifications