Phase 1B/2 Clinical Trial Assessing the Safety, Tolerability and Preliminary Efficacy of the Intravenous Administration of Allogeneic Placental Mesenchymal Cells for the Preemptive Treatment of Patients At Risk for Acute Kidney Injury Following Cardiac Surgery (MesAKI)

Phase 1B/2 Clinical Trial Assessing the Safety, Tolerability and Preliminary Efficacy of the Allogeneic Placental Mesenchymal Cells for the Preemptive Treatment of Patients At Risk for Acute Kidney Injury Following Cardiac Surgery

This clinical trial is designed to evaluate KELI-101 versus placebo for the prevention of acute kidney disease leading to chronic kidney disease in subjects at high risk for acute kidney injury following cardiac surgery. Half of the participants will receive KELI-101, while the other half will receive a placebo.

Study Overview

• Status: Not yet recruiting
• Conditions: Preemptive Therapy of Patients At Risk for Acute Kidney Injury Following Cardiac Surgery
• Intervention / Treatment: Drug: KELI-101; Other: Vehicle (placebo)

• Study Type: Interventional
• Enrollment (Estimated): 91
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Justinas Maciulaitis; Phone Number: +37068504325; Email: justinas.maciulaitis@keli.eu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Pre-operative

1. Age ≥ 45 years at screening.
2. Weigh at least 50 kg and maximum 150 kg to participate in the study and must have a body mass index (BMI) below 40; BMI = Body weight (kg) / [Height (m)]2.
3. Estimated kidney volume within normal ranges (110-190 ml for male and 90-150 ml for female, ultrasound method, ellipsoid formula)
4. High risk for AKI post CABG development as assessed by investigator e.g., >9 points by Acute Renal Failure after Cardiac Surgery (Thakar Score, Cleveland Clinic Score)

5. At screening, vital signs (systolic and diastolic blood pressure and pulse rate) will be assessed in the sitting position. Sitting vital signs should be within the following ranges:

   1. oral body temperature between 35.0-37.5 °C
   2. blood pressure (systolic 100-160 mmHg, diastolic < 100 mmHg)
   3. pulse rate (50-100/min) stable with or without medication(s) as per Investigator assessment.
6. Have a pre-operative (baseline) SCr and uNGAL collected within 30 days of surgery (if multiple laboratory results are available within this time window, the most recent SCr and uNGAL values before surgery will be used to establish the baseline)
7. No known change (increase or decrease) in SCr of ≥25% and uNGAL >200% at screening visit compared to a previous value not older than 6 weeks as documented by a local laboratory using standard assay methodology.
8. Willing and able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up.

9. Ability to give informed consent or have a legally acceptable representative do so for them.

   Peri-operative

10. Non-emergent cardiovascular surgery utilizing CPB with >1 hr duration time. Post-operative
11. ≥ 200% rise in uNGAL and uNGAL/Cr from baseline AND above cut-off of 34 ng/mg Cr (in nonCKD patients) within 4 hours of removal from CPB [the timeline and cut-off values TBD after Phase 1 (IA1)]

Exclusion Criteria:

Pre-operative

1. eGFR at screening <30 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation), or on dialysis.
2. Currently receiving renal replacement therapy.

3. Patients with bleeding risk at screening. The Investigator should make this determination in consideration of the participant's medical history and/or clinical or laboratory evidence of any of the following:

   1. History of bleeding with suspected or confirmed bleeding disorder or any other high risk for bleeding in the opinion of the investigator.
   2. Thrombocytopenia: platelet count< 100x109/L
   3. Platelet dysfunction: e.g., ADP-induced platelet aggregation lower than 60 %.
   4. Pre-existing coagulation factor deficiency: including, but not limited to, fibrinogen < 2.5-2.8 g/L
4. Any emergency surgeries performed less than 30 days before screening, including aortic dissection and/or significant congenital heart defects.
5. Class IV heart failure according to the functional classification of the New York Heart Association (NYHA).
6. Left ventricular ejection fraction < 30% (based on the last available cardiac ultrasound).
7. Scheduled to undergo cardiac surgery off CPB or with hypothermic circulatory arrest.
8. Cardiogenic shock or hemodynamic instability within four weeks before surgery, requiring inotropes or vasopressors or mechanical devices such as intra-aortic balloon counter-pulsation (IABP).
9. Have received cardiopulmonary resuscitation (CPR) within 30 days before cardiac surgery.
10. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or until the expected pharmacodynamic (PD) effect has returned to baseline, whichever is longer; or longer if required by local regulations.
11. Patients who are post-nephrectomy
12. Uncontrolled diabetes (glycolyzed HGB <7 or another cut-off as per clinical guidelines for a particular patient)
13. Have ongoing sepsis, history of sepsis or uncontrolled infection within the past 8 weeks or untreated diagnosed infection before screening visit. Sepsis is defined as the presence of a confirmed pathogen, along with fever or hypothermia and hypoperfusion or hypotension.
14. Prescribed nephrotoxic medicines (aminoglycosides, glycopeptides, radiocontrast or other agents) within the past week, leading to increased sCr >25%
15. Recent (within the last three years) and/or recurrent history of autonomic dysfunction (e.g., recurrent episodes of fainting, palpitations, etc.).
16. Pregnant or nursing (lactating) women

17. Women of child-bearing potential are defined as all women physiologically capable of becoming pregnant unless they are using highly effective methods of contraception while taking study treatment and until the end of the study. Highly effective contraception methods include:

    1. Total abstinence (when this is in line with the preferred and usual lifestyle of the participant. Periodic abstinence (e.g., calendar, ovulation, post-ovulation methods) and withdrawal are not acceptable methods of contraception.
    2. Female bilateral tubal ligation, female sterilization (have had surgical bilateral oophorectomy with or without hysterectomy) or total hysterectomy at least six weeks before taking study treatment. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment.
    3. Male sterilization (at least 6 months before screening). For female participants in the study, the vasectomized male partner should be the sole partner for that participant.
    4. Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS), or other forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for example, hormone vaginal ring or transdermal hormone contraception Peri-, postoperative
18. Anemia and hemotransfusion.
19. History of oncological disorders.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Quadruple

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Other: Vehicle (placebo); Plasmalyte
Experimental: Low dose	Drug: KELI-101; KELI-101 consists of ex vivo expanded placental mesenchymal stromal cells (PMSCs) in a 10% cryopreservation solution.
Experimental: High dose	Drug: KELI-101; KELI-101 consists of ex vivo expanded placental mesenchymal stromal cells (PMSCs) in a 10% cryopreservation solution.
No Intervention: Historical matched-control group
Experimental: Best dose	Drug: KELI-101; KELI-101 consists of ex vivo expanded placental mesenchymal stromal cells (PMSCs) in a 10% cryopreservation solution.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-emergent adverse events (TEAE)	To assess the acute and middle-term toxicity of the intrarenal arterial administration of KELI -101	From KELI -101 administration up to Day 90
Ratio of the acute kidney disease (AKD) leading to chronic kidney disease (CKD)	To assess the effect of KELI -101 on AKD leading to CKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	From baseline to Day 90

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events (AE) and adverse drug reactions (ADRs)	To assess tolerability and all AE (related or not related to study drug) after IRA administration of KELI -101	From KELI -101 administration up to Day 90
Serious AE (SAE) and Serious ADRs (SADRs)	To assess all serious AE (related or not related to study drug) after IRA administration of KELI -101	From KELI -101 administration up to Day 90
Ratio of the highest SCr value within 6 days post-dose versus baseline	To assess the effect of KELI -101 on SCr level, versus mean matched historical control SCr level	From baseline to Day 7
AKI stages 1, 2 and 3 as defined by modified AKI Network criteria	To assess the effect of KELI -101 on the incidence and severity of AKI in high-risk patients undergoing major cardio-vascular surgery, versus mean matched historical control SCr level For historical control: To assess the incidence and severity of AKI in high-risk patients undergoing major cardiovascular surgery in relation to preoperative Scr levels.	From baseline to Day 7
Ratio of the duration of AKI/AKD at Day 28	To assess the effect of KELI -101 on duration of AKI/AKD	From baseline to Day 28
Ratio of incidence and duration of renal replacement therapy (RRT) Day 28	To assess the effect of KELI -101 on incidence and duration of RRT	From baseline to Day 28
Occurrence of major adverse kidney event (MAKE) at Day 7/10/30/90 (MAKE7/10/30/90)	To assess the effect of KELI -101 on Major Adverse Kidney Events composite (MAKE7/10/30/90)	From Day 7 to Day 90
Occurrence of major adverse reno cardiovascular event at Day 7/10/30/90 (MARCE7/10/30/90)	To assess the effect of KELI -101 on Major Adverse Reno Cardiovascular Events composite (MARCE7/10/30/90)	From Day 7 to Day 90
Ratio of the AKI leading to CKD	To assess the effect of KELI -101 on incidence of AKI to CKD transition;	From baseline to Day 90
Ratio of duration of stay in ICU	To assess the effect of KELI -101 on length of ICU-stay	From baseline to discharge from ICU
Ratio of incidence and completeness of recovery of AKI/AKD at Day 90	To assess the effect of KELI -101 on complete or partial recovery and non-recovery of AKI/AKD	From baseline to Day 90
Ratio of CKD severity as per eGFR and albuminuria at Day 90	To assess the effect of KELI -101 on sustained decline in renal function	Day 90
For matched control cohort: Increased uNGAL and uNGAL/Cr in patients that develop AKI	To assess the magnitude of Increased uNGAL and uNGAL/Cr values in urine in patients that develop AKI as compared to those without developed AKI (21 patients for AKI patients and 10 non-AKI patients' cohorts)	Timepoints of 3 Pre-CPB (D-30, D-10 to D-3 and D-1) and 5 (6) after CPB initiation: (CPB-H2, CPB-H3-4, CPB-H5-6, CPB-H9-12, (CPB-H24), and one immediately post-CPB time point (+5 to 15 min), optional
For matched control cohort: Prognostic value of increased uNGAL and uNGAL/Cr, duration, and area under curve in patients that develop AKI as compared to patients that do not develop AKI	To assess the magnitude of Increased uNGAL and uNGAL/Cr values, duration, and area under curve in patients that develop AKI as compared to those without developed AKI (21 patients for AKI patients and 10 non-AKI patients' cohorts)	Timepoints of 3 Pre-CPB (D-30, D-10 to D-3 and D-1) and 5 (6) after CPB initiation: (CPB-H2, CPB-H3-4, CPB-H5-6, CPB-H9-12, (CPB-H24), and one immediately post-CPB time point (+5 to 15 min), optional
Ratio of the acute kidney disease (AKD) at Day 10 leading to chronic kidney disease (CKD) at Day 90	To assess the effect of KELI -101 on AKD leading to CKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	From baseline to Day 90
Ratio of incidence and duration of RRT Day 28	To assess the effect of KELI -101 on incidence and duration of RRT	From baseline to Day 28
Occurrence of major adverse kidney event at Day 90 (MAKE90)	To assess the effect of KELI -101 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	Day 90
Occurrence of major adverse kidney event at Day 30 (MAKE30)	To assess the effect of KELI -101 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	Day 28+2 (Phone call)
Occurrence of individual components of the MAKE criteria at Days 30 or 90	To assess the effect of KELI -101 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	Day 28+2 (Phone call)
Occurrence of individual components of the MARCE criteria at Days 7/10/30/90	To assess the effect of KELI -101 on the incidence of AKD in high-risk patients undergoing major cardio-vascular surgery, versus placebo	From Day 7 to Day 90
CKD severity as per eGFR and albuminuria at Day 90	To assess the effect of KELI -101 on sustained decline in renal function	Day 90

Collaborators and Investigators

• Sponsor: Kelifarma

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027

Study Registration Dates

• First Submitted: November 5, 2024
• First Submitted That Met QC Criteria: November 5, 2024
• First Posted (Estimated): November 7, 2024

Study Record Updates

• Last Update Posted (Estimated): November 7, 2024
• Last Update Submitted That Met QC Criteria: November 5, 2024
• Last Verified: November 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Renal Insufficiency; Acute Kidney Injury; Wounds and Injuries
• Other Study ID Numbers: KELI-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No