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

NCT06678399 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: KELI-101
• Study Type: interventional
• Target: 91
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Preemptive Therapy of Patients At Risk for Acute Kidney Injury Following Cardiac Surgery

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (21)

• Adverse events (AE) and adverse drug reactions (ADRs)

  From KELI -101 administration up to Day 90

• Serious AE (SAE) and Serious ADRs (SADRs)

  From KELI -101 administration up to Day 90

• Ratio of the highest SCr value within 6 days post-dose versus baseline

  From baseline to Day 7

• AKI stages 1, 2 and 3 as defined by modified AKI Network criteria

  From baseline to Day 7

• Ratio of the duration of AKI/AKD at Day 28

  From baseline to Day 28

Study Arms (5)

Low dose

EXPERIMENTAL

Drug: KELI-101

High dose

EXPERIMENTAL

Drug: KELI-101

Historical matched-control group

NO INTERVENTION

Best dose

EXPERIMENTAL

Drug: KELI-101

Placebo

PLACEBO COMPARATOR

Other: Vehicle (placebo)

Interventions

KELI-101 DRUG

KELI-101 consists of ex vivo expanded placental mesenchymal stromal cells (PMSCs) in a 10% cryopreservation solution.

Best dose; High dose; Low dose

Vehicle (placebo) OTHER

Plasmalyte

Placebo

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pre-operative
• Age ≥ 45 years at screening.
• 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.
• Estimated kidney volume within normal ranges (110-190 ml for male and 90-150 ml for female, ultrasound method, ellipsoid formula)
• 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)
• 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:
• oral body temperature between 35.0-37.5 °C
• blood pressure (systolic 100-160 mmHg, diastolic \< 100 mmHg)
• pulse rate (50-100/min) stable with or without medication(s) as per Investigator assessment.
• 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)
• 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.
• Willing and able to comply with visit schedule and study procedures including post-hospitalization discharge follow-up.
• Ability to give informed consent or have a legally acceptable representative do so for them.
• Peri-operative
• Non-emergent cardiovascular surgery utilizing CPB with \>1 hr duration time. Post-operative

You may not qualify if:

• Pre-operative
• eGFR at screening \<30 mL/min/1.73 m2 (calculated using CKD-EPI 2021 equation), or on dialysis.
• Currently receiving renal replacement therapy.
• 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:
• History of bleeding with suspected or confirmed bleeding disorder or any other high risk for bleeding in the opinion of the investigator.
• Thrombocytopenia: platelet count\< 100x109/L
• Platelet dysfunction: e.g., ADP-induced platelet aggregation lower than 60 %.
• Pre-existing coagulation factor deficiency: including, but not limited to, fibrinogen \< 2.5-2.8 g/L
• Any emergency surgeries performed less than 30 days before screening, including aortic dissection and/or significant congenital heart defects.
• Class IV heart failure according to the functional classification of the New York Heart Association (NYHA).
• Left ventricular ejection fraction \< 30% (based on the last available cardiac ultrasound).
• Scheduled to undergo cardiac surgery off CPB or with hypothermic circulatory arrest.
• 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).
• Have received cardiopulmonary resuscitation (CPR) within 30 days before cardiac surgery.
• 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.

Sponsors & Collaborators

• Kelifarma: lead

Central Study Contacts

Justinas Maciulaitis

CONTACT

+37068504325; justinas.maciulaitis@keli.eu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2024
• First Posted: November 7, 2024
• Study Start: April 1, 2025
• Primary Completion (Estimated): October 1, 2026
• Study Completion (Estimated): January 1, 2027
• Last Updated: November 7, 2024

Record last verified: 2024-11