A Trial to Assess Efficacy and Safety of ex Vivo Allograft Admin of iCM012 Solution 2 mg/ml to Improve Its Function in Recipients of DCD Kidneys

A Randomized, Placebo-controlled, Double-blind Phase 2b Trial to Assess the Efficacy and Safety of ex Vivo Allograft Admin of iCM012 Solution 2 mg/mL to Improve Allograft Function in Recipients of Donation After Circulatory Death Kidneys

Randomized (1:1), placebo controlled, double blind efficacy trial. 200 patients will be followed up for 12 months post transplantation. The primary endpoint will be Delayed Graft Function (DGF) defined as the requirement for dialysis within 7 days post transplantation.

Study Overview

• Status: Not yet recruiting
• Conditions: Ischemia-reperfusion Injury; Kidney Transplant; Complications
• Intervention / Treatment: Drug: iCM012 solution 2 mg/mL; Drug: Placebo

Detailed Description

The present trial aims to evaluate if iCM012 solution 2 mg/mL can improve short and mid-term allograft function of controlled donation after circulatory death (DCD) kidneys at high risk for Ischemia Reperfusion Injury (IRI) -induced graft dysfunction as assessed by primarily DGF and secondary as estimated glomerular filtration rates (eGFR). The trial will also generate additional efficacy, safety, and exploratory data.

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Ingegerd Dalfelt; Phone Number: 46708433348; Email: ingegerd.dalfelt@icoatmedical.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

To be eligible for use in this trial, an allograft must meet the following criterion:

1. Controlled DCD donors Maastricht category III from 55 to 75 years of age.

   To be eligible to participate in this trial, a patient must meet all the following criteria:

2. Available, personally signed and dated Informed Consent Form.
3. Male or female chronic kidney disease (CKD) ≥ 18 years of age, on dialysis > 12 months, awaiting their first kidney transplantation.
4. AB0-compatible, negative pre-transplantation Complement Dependent Cytotoxicity (CDC) and/or flow cytometric class I and II crossmatch, or negative virtual class I and II crossmatch, and no pre-existing donor specific antibodies (Mean Fluorescent Intensity under center specific cut-off for negative value).
5. Completed vaccination program according to local standard practice or as deemed relevant by the investigator.

Exclusion Criteria:

An allograft that meets any of the following criteria will be excluded from use in this trial:

1. Surgically induced injuries or anatomical vascular variations compromising ex vivo treatment and/or transplantation outcome, as judged by the investigator.
2. DCDs with persistent and significant deterioration of kidney function (30% decrease in eGFR from baseline) and/or on dialysis within two (2) weeks prior to organ procurement and/or anuria > 12 hours before surgery.

3. Extracorporeal membrane oxygenation treatment of the donor

   A patient who meets any of the following criteria will be excluded from participation in this trial:

4. If not tolerating/eligible for thymoglobulin induction and tacrolimus or Cyclosporine A (CyA)-based maintenance immunosuppressants.
5. Previously undergone any organ and/or cell transplantations.
6. Positive CDC and or flow cytometric class I and/or II crossmatch, and/or positive virtual crossmatch.
7. Highly sensitized patients defined by Panel Reactive Antibody (PRA) level equal or higher than 98%.
8. AB0-incompatible deceased donor kidney transplantation.
9. Pregnant or breast-feeding woman.
10. Woman of child-bearing potential, not using an adequate contraceptive method.
11. Prior participation in a clinical trial with (approved or non-approved) IMPs within 1 month prior to screening for this trial.
12. Prior malignancy diagnosis ≤ 5 years, except for adequately treated basal cell, or squamous cell skin cancer, and carcinoma in situ, or judged as irrelevant by the investigator.
13. Positive result for serum human immunodeficiency virus (HIV), active hepatitis B or C infection in pre-transplantation evaluation.
14. History of severe drug allergy or hypersensitivity, or known hypersensitivity, or intolerance to any of the IMPs or its/their excipients.
15. Concomitant severe conditions requiring treatment and close monitoring, as judged by the investigator.
16. History of any other clinically significant disease or disorder which, in the opinion of the investigator, may either put the patient at increased risk because of participation in the trial, or influence the results or the patient's ability to participate in the trial.
17. Unlikely to comply with trial procedures, restrictions, and requirements (e.g., caused by substance abuse, concurrent medical condition, etc.), as judged by the investigator.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active treatment iCM012 solution 2 mg/mL; iCM012 solution 2 mg/mL - 200 mL Investigational Medicinal Product (IMP) solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.	Drug: iCM012 solution 2 mg/mL; 200 mL IMP solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.
Placebo Comparator: Placebo; Placebo - 200 mL IMP solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.	Drug: Placebo; 200 mL IMP solution is administered ex vivo by gravity as single infusion through the renal artery/-ies over a period of 5-10 minutes.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Delayed Graft Function (DGF)	DGF is defined as the need for dialysis within the first 7 postoperative days.	First 7 postoperative days.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
eGFR over 12 months post transplantation	Estimated Glomerular Filtration Rate using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation with four (4) variables (serum creatinine, age, gender, and ethnicity)	12 months post transplantation
Primary non-function	Primary non-function (PNF) describes the condition in which the kidney never functions adequately after transplantation, and the patient continues to need dialysis despite the transplantation. The diagnosis of PNF generally does not become established before 2 to 3 months after transplantation. Assessed up to 12 months after transplantation	12 months post transplantation
Number of Participants with prolonged DGF	Number of Participants with prolonged DGF (defined as requirement for dialysis more than 14 days post transplantation)	14 days post transplantation
Number of Participants with functional DGF	Number of Participants with functional DGF (defined as no serum creatinine decrease by at least 10% daily on 3 consecutive days within the first 7 days post-transplantation)	First 7 days post-transplantation
Duration of dialysis sessions (hours)	Duration of dialysis sessions within the first 30- and 90-days post-transplantation. Measured in hours.	First 30- and 90-days post-transplantation
Number of dialysis sessions	Number of dialysis sessions within the first 30- and 90-days post-transplantation	First 30- and 90-days post-transplantation
Changes in Quality of Life	Quality of Life EuroQol - five dimensions - three levels (EQ-5D-3L) Assessed through standardized questionnaires, results combined to single summary index (0-1: 0 is death, 1 is perfect health).	12 months post transplantation
Incidence of de novo Human Leukocyte Antigen (HLA) antibodies within 12 months	Incidence of de novo Human Leukocyte Antigen antibodies within 12 months	12 months post transplantation
Incidence of biopsy-proven allograft rejection within 12 months	Incidence of biopsy-proven allograft rejection within 12 months	12 months post transplantation
Tubular cell injury assessed by exploratory urinary biomarkers	Tubular cell injury assessed by exploratory urinary biomarkers; details not yet decided.	12 months post transplantation

Collaborators and Investigators

• Sponsor: iCoat Medical AB
• Investigators: Study Chair: Ingegerd Dalfelt, iCoat Medical

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2025
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: August 27, 2024
• First Submitted That Met QC Criteria: August 30, 2024
• First Posted (Actual): September 3, 2024

Study Record Updates

• Last Update Posted (Actual): April 3, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: kidney transplantation; Ex-vivo kidney allograft treatment; Transplant outcome; Ischemia-reperfusion Injury
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Postoperative Complications; Pathologic Processes; Ischemia; Reperfusion Injury
• Other Study ID Numbers: EMPIRe; 2024-513990-33-00 (Ctis)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data (IPD) collected in this study will be made available to participating trial patients through the investigational site and to the public through publications.
• IPD Sharing Time Frame: After End of Trial
• IPD Sharing Access Criteria: Individual participant data (IPD) collected in this study will be made available to participating trial patients through the investigational site and to the public through publications, as well as on the company website.
• IPD Sharing Supporting Information Type: CSR

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