Modified Autologous Leukocyte Cells for the Treatment of Acute Kidney Injury After Cardiac Surgery

M2RLAB SL

Status and phase: Not yet enrolling; Phase 2

Conditions: Acute Kidney Injury

Treatments: Drug: M2RLAB 001; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT07052513

M2R.AKI.2021

2023-504610-30-01 (EU Trial (CTIS) Number)

Details and patient eligibility

About

The purpose of this clinical trial is to assess the efficacy and safety of cell therapy with modified leukocyte cells from the participant himself/herself versus placebo in patients who develop Acute Kidney Injury (AKI) within the first 48 hours after cardiac surgery.

The main questions it aims to answer are:

• Does cell therapy reduce the recovery time of kidney function?
• What medical problems do participants have when receiving cell therapy?

Researchers will compare cell therapy with a placebo (a look-alike substance that contains no drug) to see if cell therapy works to treat AKI. The safety of cell therapy with leukocyte cells will also be studied.

Full description

This is a Phase II, multi-center, randomized, placebo-controlled clinical trial, with 2 treatment arms and single blind. After being informed about the study, participants who meet the eligibility criteria will be randomized in 1:1 ratio to treatment with a single administration of cell therapy with leukocyte cells from the participant himself/herself or placebo (approximately 49 subjects per group).

Acute kidney injury (AKI) is one of the main complications after cardiac surgery. In fact, AKI after cardiac surgery is associated with high morbidity and mortality. Currently, there are no effective therapies for kidney injury after cardiac surgery, but there is evidence that recovery is possible if the injury processes are overcome. Thus, due to the lack of preventive and therapeutic options at present, cell therapy has gained importance in recent years in different clinical trials. Thus, within this context, the use of modified leukocyte cells as cell therapy is also an alternative for the treatment of AKI due to their powerful immunomodulatory effect. On the other hand, the use of placebo is justified because there is currently no other pharmacological treatment available to serve as an active control. A placebo-controlled study is optimal to evaluate the efficacy and safety of an experimental treatment.

Researchers hypothesized that cell therapy with autologous leukocyte cells can be safe, well tolerated and clinically beneficial versus placebo for participants who develop AKI within the first 48 hours after cardiac surgery.

This study consists of 3 phases: the initial phase, the observation phase, and the follow-up phase. The total duration of each participant in the trial will be 3 months:

• Initial phase: The patient undergoing cardiac surgery will sign the informed consent (IC) before the surgery (at a scheduled visit prior to his/her hospitalization or at the time of his/her hospitalization and prior to undergoing the procedure). As indicated in the Inclusion criteria, only participants who present AKI within the first 48 hours post cardiac surgery will be included. The participants who meet all the inclusion criteria and none of the exclusion criteria will be randomized in a 1:1 ratio to one of the two study groups. A volume of at least 60 mL of peripheral blood will be extracted from the patient, from which the cell therapy will be prepared (in cases where the patient is included in the experimental group) The investigational product/placebo will be administered to the patient within 36 hours of AKI diagnosis.
• Observation phase: It includes the period from when the patient receives the investigational drug/placebo until he or she is discharged from the hospital. This period lasts 16 to 20 days, depending on the clinical evolution of the participants. During this phase, participants will be followed and will undergo different tests in order to evaluate the effectiveness and safety of the investigational treatment vs. placebo.
• Follow-up phase: It includes the period from when the patient receives hospital discharge and ends 90 days from the date of inclusion of the participant in the study. At this stage, participants will be monitored to evaluate the efficacy and safety of the experimental cell therapy drug vs. placebo.

Enrollment: 98 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. Male or female participants older than 18 years of age, being able to understand and sign the Informed Consent.

2. Participants undergoing elective valvular and/or coronary cardiac surgery performed with extracorporeal circulation.

3. Present pre-operative AKI risk more or equal to 30 percent according to the Leicester Cardiosurgery scale.

4. Present AKI within the first 48 hours post cardiac surgery in one of the following classifications defined by the AKIN scale (Acute Kidney Injury Network):

   AKIN 1: An increase in serum creatinine by at least 0.3 mg/dL (more or equal to 26.4 micromol/L) from baseline, or an increase to more or equal to 150-200 percent (corresponding to a 1.5- to 2-fold increase) from baseline. In addition, the patient must have a positive acute tubular necrosis score within the first 48 hours post cardiac surgery, defined as the presence of at least 3 of the following 4 scenarios: Sodium excretion fraction more than 2 percent, urinary osmolality lower than 400 mOsm/kg, urine sodium more than 40 mmol/L, presence of shock or nephrotoxic agents.

   AKIN 2: An increase in serum creatinine to more than 200 percent and up to a maximum of 300 percent (corresponding to an increase of more than 2 and up to 3 times) over baseline.

   AKIN 3: An increase in serum creatinine to more than 300 percent (corresponding to more than 3-fold increase) over baseline, or an increase in serum creatinine levels to more or equal to 4.0 mg/dl (more or equal to 354 micromol/l) with an acute increase of at least 0.5 mg/dl (44 micromol/l).

5. In the case of women or men of childbearing age, for safety, those who undertake to follow the contraceptive measures required from their discharge from hospital until the end of their participation in the clinical trial.

Exclusion criteria

1. Chronic Kidney Disease (CKD) in stage IV or V (glomerular filtration rate [GFR] less than 30 ml/min).
2. AKI one month prior to heart surgery.
3. Participants who have previously undergone renal therapy.
4. Participants who are scheduled to start renal replacement therapy within the next 72 hours.
5. Interstitial glomerulonephritis or vasculitis.
6. Pregnancy.
7. Women in breastfeeding period
8. Renal transplant history.
9. Endocarditis.
10. Participants with mechanical assistance devices: extracorporeal membrane oxygenation (ECMO), left ventricular assist device (LVAD), right ventricular assist device (RVAD), intra-aortic balloon pumps (IABP).
11. Known severe ventricular dysfunction (left ventricular ejection fraction [LVEF] less than 30 percent).
12. Post-surgical septic infectious condition.
13. Positive serology for hepatitis C virus (HCV), hepatitis B virus antigen (HBSAg), human immunodeficiency virus (HIV) or syphilis (by VDRL/TP: Venereal Disease Research Laboratory/Treponema pallidum). This criterion will be assessed once it has been confirmed that the patient has developed AKI.
14. Participants enrolled in another clinical trial testing.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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98 participants in 2 patient groups, including a placebo group

Saline Solution for injection

Placebo Comparator group

Description:

Participants randomized to placebo will receive a single 10 mL dose Intravenous (IV) infusion of normal saline (0.9 percent) no later than 36 hours after the participant's diagnosis of AKI and inclusion in the study.

Treatment:

Drug: Placebo

Cell therapy with leukocyte cells from the participant himself/herself

Experimental group

Description:

Participants randomized to experimental group will receive a single 10 mL dose IV of leukocyte cells concentration of 6-15.4 x10\^6 cells/mL no later than 36 hours after the participant's diagnosis of AKI and inclusion in the study.

Treatment:

Drug: M2RLAB 001