A Danish, double-blind, randomized placebo-controlled clinical trial evaluating allogeneic adipose tissue derived mesenchymal stromal cell therapy in patients with recently diagnosed non-ischemic heart failure with reduced ejection fraction.

The primary objective of this trial is to investigate the efficacy and safety of intravenous infusion of allogeneic adipose tissue-derived mesenchymal stromal stem cells (C2C_ASC110) in patients with recently diagnosed non-ischemic heart failure with reduced ejection fraction in restoring cardiac function compared to placebo (CryoStor CS10). This objective addresses the clinical need for therapeutic interventions capable of restoring myocardial function in patients with newly diagnosed non-ischemic cardiomyopathy, a condition associated with progressive ventricular dysfunction and adverse clinical outcomes.

The sponsor did not provide information regarding the total number of participants enrolled in this clinical trial. The study population included both male and female adults over 18 years of age and elderly participants. Participants were diagnosed with non-ischemic heart failure with reduced ejection fraction. Key selection criteria included an initial left ventricular ejection fraction (LVEF) of 40% or less, with subsequent medication optimization within the preceding 12 months, and a current LVEF of 45% or less documented by echocardiography, CT, or MRI. Participants exhibited symptomatic heart failure classified as NYHA (New York Heart Association) class II to III. Elevated plasma Pro-BNP levels were required, with thresholds of greater than 300 pg/ml in patients with sinus rhythm and greater than 422 pg/ml in those with atrial fibrillation. The trial did not involve vulnerable populations. No specific information regarding lifestyle considerations such as diet, physical activity, or habits was provided by the sponsor.

This clinical trial investigates the efficacy and safety of intravenous infusion of allogenic adipose-tissue-derived mesenchymal stem cells (C2C_ASC110) in patients with recently diagnosed non-ischemic heart failure with reduced ejection fraction compared to placebo (CryoStor CS10). The study is designed as a double-blind, randomized, placebo-controlled trial conducted in Denmark. The trial is classified as a Phase II efficacy and safety study. The investigational product C2C_ASC110 contains allogenic adipose-tissue-derived mesenchymal stem cells administered via infusion, with a maximum daily dose of 110 million organisms and a maximum total dose of 220 million organisms over a treatment period of one day. The placebo consists of CryoStor CS10, a freezing medium containing DMSO used in the cryopreservation and formulation of the investigational product.

The primary efficacy endpoint is the change in left ventricular ejection fraction (LVEF) at 6 months after the last C2C_ASC110 infusion compared to the placebo group. Secondary efficacy endpoints include changes in left ventricular end-systolic volume (LVESV), LVEF, and left ventricular end-diastolic volume (LVEDV) at 7 and 12 months follow-up. Additional secondary endpoints assess changes in NYHA classification, 6-minute walking test results, KCCQ and EQ5D5L questionnaire scores, supplementary echocardiographic measures, and Pro-BNP levels. Safety endpoints include the incidence and severity of serious adverse reactions (SARs) and suspected unexpected serious adverse reactions (SUSARs) evaluated at 12 months follow-up.

Principal inclusion criteria require participants to be over 18 years of age, diagnosed with non-ischemic heart failure with initial LVEF ≤ 40% and subsequently up-titrated to maximal tolerable heart failure medication within the last 12 months, symptomatic heart failure (NYHA II-III), LVEF ≤ 45% documented by echocardiography, CT, or MRI after medication up-titration, and elevated plasma Pro-BNP levels (> 300 pg/ml in sinus rhythm or > 422 pg/ml in atrial fibrillation). For patients receiving an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronisation Therapy (CRT), reduced LVEF must be documented at least after 1 and 3 months, respectively.

The estimated recruitment start date is February 2, 2026, with an estimated trial end date of February 2, 2029, resulting in an overall trial duration of approximately three years. Participant involvement extends through the 12-month follow-up period following treatment administration. The study protocol includes a screening visit for eligibility assessment, treatment administration visit, and follow-up visits at 6, 7, and 12 months post-treatment to evaluate efficacy and safety outcomes. Conditions that may lead to early termination from the study are not specified in the provided information.

The experimental treatment consists of C2C_ASC110, an allogeneic adipose-tissue-derived mesenchymal stem cell therapy administered via intravenous infusion. The active substance comprises allogenic adipose-tissue-derived mesenchymal stem cells, which represent a structurally diverse substance classified as cell therapy. The product is manufactured by Cell2Cure APS and is also referred to as CellReady. The maximum daily dose is 110 million organisms, with a maximum total dose of 220 million organisms administered over the treatment period of 1 day. The pharmaceutical form is designed for infusion delivery, and the therapy is categorized as an advanced therapy medicinal product of cell origin with somatic cell type characteristics.

The comparator treatment in this double-blind, randomized, placebo-controlled clinical trial is CryoStor CS10, which serves as the placebo. CryoStor CS10 is a freezing medium for cells that contains dimethyl sulfoxide (DMSO) at a concentration of 10%. This product has been utilized for cryopreservation of C2C_ASC110 and is incorporated within the formulation of C2C_ASC110 as an excipient. CryoStor CS10 is a serum-free, animal component-free product manufactured according to current Good Manufacturing Practice (cGMP) principles and formulated with United States Pharmacopeia (USP)-grade components to minimize variability. The product has been previously used as an excipient for cryopreservation in other approved cell-based therapies, including genetically modified autologous cell products for treatment of blood cancers that have received marketing authorization in the European Union, United States, and Canada. CryoStor CS10 is not regarded as a novel excipient due to its established use in approved medicinal products.

Efficacy will be assessed using **left ventricular ejection fraction (LVEF)** as the primary endpoint. The primary efficacy endpoint is the change in LVEF at 6 months after the last infusion of C2C_ASC110 compared to the placebo group receiving CryoStor CS10 infusion. Secondary efficacy endpoints include changes in **left ventricular end-systolic volume (LVESV)**, LVEF, and **left ventricular end-diastolic volume (LVEDV)** at 7 and 12 months follow-up. Additional secondary efficacy endpoints encompass changes in **NYHA classification**, 6-minute walking test, KCCQ and EQ5D5L questionnaire responses, additional echocardiographic measures, and **Pro-BNP** levels. LVEF will be documented by echocardiography, CT, or MRI performed after up-titration of **heart failure** medication. Safety endpoints include the incidence and severity of serious adverse reactions and suspected unexpected serious adverse reactions evaluated at 12 months follow-up.