ASCs in Recently Diagnosed Non-ischemic Heart Failure (ARIISE)

Cell to Cure ApS

Status and phase: Begins enrollment this month; Phase 2

Conditions: Non-Ischemic Heart Failure; Reduced Ejection Fraction Heart Failure

Treatments: Other: Cryostor CS10; Drug: Allogeneic adipose tissue-derived mesenchymal stem cells

Study type: Interventional

Funder types: Industry

Identifiers

NCT06840275

U1111-1315-7011 (Other Identifier)

ARIISE

2025-520837-22-00 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The goal of this clinical trial is to investigate the efficacy and safety of intravenous infusions of allogeneic adipose tissue-derived mesechymal stromal cells in patients with recently diagnosed non-ischemic heart failure in restoring cardiac function compared to placebo. The primary outcome of this trial is the change in left ventricular ejection fraction 6 month after treatment compared to placebo. Participants will be given two treatments with one month apart of either allogeneic adipose tissue-derived mesechymal stromal cells or placebo.

Full description

Non-ischemic heart failure (NIHF) is the leading reason for heart transplantation. The disease can be caused by several different factors, which include genetic disposition, inflammation, hypertension, alcohol consumption, and arrhythmia. Regardless of the aetiology, immune activation in myocardium leads to collagen deposition and decreases the function of heart. There are currently no treatment options, which reverse the inflammatory component in NIHF.

For the past decade, cell therapy has been tested as treatment option for ischemic and non-ischemic heart failure. Especially the mesenchymal stromal cell (MSC) has shown encouraging results for their potential to improve cardiac function in patients with non-ischemic heart failure along with its safety. The cardiac improvement may be related to the immunomodulation as MSC is known by its ability to modulate the immune system and has successfully been applied clinically as a novel active immunosuppressor.

We aim to conduct a clinical trial in which patients recently diagnosed with NIHF will be randomized to either treatment with two intravenous infusions of allogeneic MSCs obtained from adipose tissue (C2C_ASC110) or placebo (Cryostor® CS10) 4 weeks apart. The objective is to evaluate the safety and effect of MSCs on cardiac function.

The long-term perspective is that the information gathered from this study can lead to a new treatment option for this specific group of patients, who currently have no further treatment options and a poor prognosis.

Enrollment: 90 estimated patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patients above 18 years of age
• Written informed consent
• Anticipated to be able to participate during the entire study period
• Diagnosed with non-ischemic heart failure with initial LVEF ≤ 40% and then 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 performed after up-titration of heart failure medication (documentation of reduced LVEF at least after 1 and 3 months if implantation of a device either an Implantable Cardioverter Defibrillator (ICD) or Cardiac Resynchronisation Therapy (CRT), respectively)
• Plasma Pro-BNP > 300 pg/ml (> 35 pmol/L) in patients with sinus rhythm and plasma Pro-BNP > 422 pg/ml (> 49 pmol/L) in patients with atrial fibrillation.

Exclusion criteria

• NYHA I or IV heart failure
• Documented ischemic heart failure
• On-going alcohol abuse
• Implantation of CRT within 3 months or ICD within 1 month
• Acute coronary syndrome with elevation of CKMB (Creatine Phosphatase-Myocardial Band) or troponins, stroke or transitory cerebral ischemia within six weeks of inclusion
• Expected to undergo screening for heart transplantation during the study time
• Listed for heart transplantation
• Other cardiac revascularization treatments to be performed
• Moderate to severe aortic stenosis (valve area < 1.1 cm2) or clinically significant mitral valve disease
• Diminished functional capacity for other reasons such as: chronic obstructive pulmonary disease (COPD) with forced expiratory volume (FEV) < 1 L/min or body mass index > 35kg/m2
• Clinically significant anaemia (haemoglobin < 6 mmol/L), leukopenia (leucocytes < 2 109/L), leucocytosis (leucocytes >14 109/L) or thrombocytopenia (thrombocytes < 50 109/L)
• History with malignant disease within five years of inclusion or current suspected malignancy - except treated skin cancer other than melanoma
• Patients with known hypersensitivity to DMSO and Dextran-40.
• Pregnant women
• Other experimental treatment within four weeks from baseline tests
• Participation in another interventional trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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90 participants in 2 patient groups, including a placebo group

Allogeneic adipose tissue-derived mesenchymal stromal cells (C2C_ASC110)

Experimental group

Description:

Intravenous infusion of allogeneic adipose tissue-derived mesenchymal stromal cells (C2C\_ASC110) 1 month apart.

Treatment:

Drug: Allogeneic adipose tissue-derived mesenchymal stem cells

CryoStor® CS10

Placebo Comparator group

Description:

Intravenous infusion of CryoStor® CS10 1 month apart.

Treatment:

Other: Cryostor CS10