CDR 132L / Hannover Medical School, Novo Nordisk - LARVOL DELTA

8212-Preserved: 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 (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Novo Nordisk A/S

Trial initiation date • Cardiovascular • Congestive Heart Failure • Heart Failure

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 (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Novo Nordisk A/S

Trial initiation date • Cardiovascular • Congestive Heart Failure • Heart Failure

NN6706-8230: A study understanding how much CDR132L enters the bloodstream after injection under the skin compared to injection into a vein in healthy participants (clinicaltrialsregister.eu) - P1 | N=32 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P1 trial • Cardiovascular • Heart Failure

Effects of CDR132L on cardiac structure and function in heart failure with preserved ejection fraction and left ventricular hypertrophy: the 8212-Preserved trial (HEART FAILURE 2026) - No abstract available

Cardiovascular • Congestive Heart Failure • Heart Failure • IL2RG

Selective inhibition of microRNA-132 with CDR132L in patients with heart failure with reduced/mildly reduced ejection fraction and left ventricular hypertrophy: the 8282-Reduced trial (HEART FAILURE 2026) - No abstract available

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • IL2RG • MIR132

Nanotechnology-driven heart targeting to fulfil the potential of cardiac microRNA therapies. (PubMed, Int J Pharm) - "Even fewer microRNA therapeutics have reached clinical trials, only CDR132L and MRG-110. Consequently, targeted microRNA nanotherapies could be pivotal in overcoming the current bottleneck and realizing the therapeutic potential of microRNAs in the heart. In conclusion, this review offers an outlook of the future applicability of microRNA therapies leveraging the latest advances in non-viral targeted delivery with nanocarriers."

Journal • Review • Cardiovascular • Heart Failure • IL2RG

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 (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

8212-Preserved: 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 (clinicaltrials.gov) - P2 | N=200 | Recruiting | Sponsor: Novo Nordisk A/S | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Congestive Heart Failure • Heart Failure

MiR-132 inhibition improves myocardial strain in a large animal model of chronic left ventricular adverse remodelling. (PubMed, Eur Heart J Imaging Methods Pract) - P1, P2 | "LV and LA motion and contractility were improved by repeated monthly dosing of CDR132L in a large animal model of HF with reduced ejection fraction model with first dose given one month post-MI. The results highlight the translational value and usability of MRI-based cardiac strain imaging in HF drug development and support further clinical development of CDR132L."

Journal • Preclinical • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • IL2RG • MIR132

8282-Reduced: 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 (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

8212-Preserved: 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 (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Novo Nordisk A/S

New P2 trial • Cardiovascular • Congestive Heart Failure • Heart Failure

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=294 | Completed | Sponsor: Cardior Pharmaceuticals GmbH | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

Novo Nordisk Gets CDSCO Panel Nod To study CDR132L (Medical Dialogues) - "Novo Nordisk has got the go-ahead from the Subject Expert Committee (SEC) functional under the Central Drug Standard Control Organisation (CDSCO) to conduct the clinical trial of CDR132L 45.2 (45,2) mg/vial, a synthetic oligonucleotide that's being developed to treat heart failure. This came after Novo Nordisk presented phase 2 clinical study protocol no. NN6706-8282 version 1.0 dated 21 November 2024."

New P2 trial • Heart Failure

Exploring the role of pericardial miRNAs and exosomes in modulating cardiac fibrosis. (PubMed, Cardiovasc Pathol) - "Presenting the first human miRNA antisense drug trial, inhibition of miR-132 by intravenous administration of a novel antisense oligonucleotide, CDR132L, established efficacy in reducing miR-132 in plasma samples in a dose-dependent manner. We screened the literature, provided an overview of the miRNAs and exosomes present in PF, and drew a connection to those miRNAs previously elucidated in cardiac fibrosis and HF. Further, we speculate about clinical implications and potential delivery methods."

Journal • Review • Atrial Fibrillation • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • Ventricular Tachycardia • IL2RG • MIR132

REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Cardior Pharmaceuticals GmbH | N=130 ➔ 0 | Not yet recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Cardiovascular • Congestive Heart Failure • Heart Failure

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=294 | Active, not recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Recruiting ➔ Active, not recruiting | Trial primary completion date: Apr 2024 ➔ Sep 2024

Enrollment closed • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

Efficacy and safety of CDR132L in patients with reduced left ventricular ejection fraction after myocardial infarction: Rationale and design of the HF-REVERT trial. (PubMed, Eur J Heart Fail) - "The HF-REVERT trial may underpin the concept of miR-132 inhibition to prevent or reverse cardiac remodelling in post-MI HF. The results will inform the design of subsequent outcome trials to test CDR132L in HF."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • MIR132

HF-REVERT: Study to Assess Efficacy and Safety of CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Trial completion date: Nov 2024 ➔ Apr 2025

Trial completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction

REMOD-REVERT: Reverse Remodeling Effects of CDR132L in Patients With Heart Failure With Mildly Reduced or Preserved Ejection Fraction and Cardiac Hypertrophy (clinicaltrials.gov) - P2 | N=130 | Not yet recruiting | Sponsor: Cardior Pharmaceuticals GmbH | Trial completion date: May 2025 ➔ Sep 2025 | Initiation date: Dec 2023 ➔ Apr 2024 | Trial primary completion date: May 2025 ➔ Sep 2025

Trial completion date • Trial initiation date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure

microRNA-132 Inhibition Improves Cardiac Function and Reduces Remodeling in Patients With Heart Failure With Reduced Ejection Fraction (HFrEF): An Exploratory Subgroup Analysis of the CDR132L First-in-Human Study (AHA 2023) - "Analysis of the HFrEF subgroup in this FiH trial, although limited by the small patient numbers, indicatively underlines the encouraging benefits of CDR132L, a novel antisense drug, on LV function and cardiac remodeling as established in previous large animal HF models."

Clinical • P1 data • Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Immunology • IL2RG • LCN2 • MIR132

Plasma miR-132 Serves as a Blood Biomarker for Monitoring Treatment Efficacy of miR-132 Targeting Drugs Using a Novel CE-Marked Kit System (AHA 2023) - P1 | "Plasma miR-132 was validated as a suitable target engagement and therapy monitoring biomarker and the newly developed CE-marked kit "CardiorHealth miR-132 Plasma PCR Kit (IVD)" fulfilled its intended use to quantify plasma miR-132 and can be used for monitoring treatment with drugs targeting miR-132."

Biomarker • Clinical • Cardiovascular • Myocardial Infarction • IL2RG • KEAP1 • MIR132

miR-132 Inhibition Shows Anti-Hypertrophic Effects in Preclinical Heart Failure Models and in Exploratory Pharmacodynamic Parameters of a First-in-Human Phase 1b Clinical Trial (AHA 2023) - P1 | "Our results confirm beneficial effects of CDR132L treatment on pathological cardiac remodeling in HF."

P1 data • PK/PD data • Preclinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • LCN2 • MIR132

miR-132 Inhibitor CDR 132L Attenuates Cardiac Remodeling by Exhibiting Anti-Fibrotic Effects (AHA 2023) - P1 | "By blocking aberrant miR-132 expression, CDR132L is capable to halt and reverse pathological cardiac remodeling partly due to its anti-fibrotic effects."

Cardiovascular • Congestive Heart Failure • Fibrosis • Heart Failure • Myocardial Infarction • IL2RG • MIR132

The Novel Antisense Oligonucleotide CDR132L Improves Cardiac Function in Heart Failure Across Different Species (AHA 2023) - "Pharmacological miR-132 inhibition by CDR132L improved cardiac function in multi-species models of HF, highlighting the therapeutic potential for clinical use in HF patients."

Cardiovascular • Congestive Heart Failure • Heart Failure • IL2RG • MIR132

Efficacy and Safety of miR-132 Inhibitor CDR132L in Patients With Reduced Left Ventricular Ejection Fraction After Myocardial Infarction: Rationale for and Design of the HF-REVERT Trial (AHA 2023) - P2 | "This trial may therefore underpin the concept of miR-132 inhibition to prevent/reverse cardiac remodeling in HF patients. The results will inform the design of a subsequent outcome trial to test the effect of CDR132L in HF patients."

Clinical • Cardiovascular • Congestive Heart Failure • Heart Failure • Myocardial Infarction • IL2RG • MIR132