Clinical trial NCT06840275: ASCs in Recently Diagnosed Non-ischemic Heart Failure
Official title: A Danish, Double-blind, Randomized Placebo-controlled Clinical Trial Evaluating Allogeneic Adipose Tissue Derived Mesenchymal Stromal Cell Therapy in Patients with Recently Diagnosed Non-ishemic Heart Failure with Reduced Ejection Fraction
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Non-Ischemic Heart Failure
Reduced Ejection Fraction Heart Failure
Keywords: allogeneic adipose tissue derived mesenchymal stromal cell
non-ischemic heart failure
mesenchymal stromal cell
Lead sponsor: Cell2Cure ApS
Sponsor class: INDUSTRY
First posted: 2025-02-21
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in left ventricular ejection fraction (I)
timeFrame: From enrollment to 6 months after the last infusion of C2C_ASC110 and placebo.
Secondary outcomes:
measure: Changes in left ventricular end systolic volume
timeFrame: From enrollment to 7 months and to 12 months.
measure: Change in left ventricular ejection fraction (II)
timeFrame: From enrollment to 7 months and to 12 months.
measure: Changes in left ventricular end diastolic volume
timeFrame: From enrollment to 7 months and to 12 months.
measure: Change in NYHA classification
timeFrame: From enrollment to 12 months.
measure: Change in KCCQ questionnaire score
timeFrame: From enrollment to 12 months.
measure: Change in EQ5D5L questionnaire score
timeFrame: From enrollment to 12 months.
measure: Change in 6 minutes walking test
timeFrame: From enrollment to 12 months.
measure: Change in Pro-BNP
timeFrame: From enrollment to 12 months.
measure: Incidence and severity of adverse reactions
timeFrame: From the first infusion of C2C_ASC110 and placebo to 12 months.
Other outcomes:
Locations:
city: København
country: Denmark
facility: Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, University of Copenhagen, Denmark
Study officials:
affiliation: Cardiology Stem Cell Centre, Department of Cardiology, The Heart Centre, Rigshospitalet, Copenhagen
name: Abbas A Qayyum, MD MSc PhD
role: PRINCIPAL_INVESTIGATOR
References: