Clinical trial NCT06582485: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Ischemia-reperfusion Injury
Kidney Transplant; Complications
Keywords: Ex-vivo kidney allograft treatment
kidney transplantation
Transplant outcome
Ischemia-reperfusion Injury
Lead sponsor: iCoat Medical AB
Sponsor class: INDUSTRY
First posted: 2024-09-03
Enrollment: 200
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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 \&gt; 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 \&gt; 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.

Primary outcomes:
measure: Delayed Graft Function (DGF)
timeFrame: First 7 postoperative days.
Secondary outcomes:
measure: eGFR over 12 months post transplantation
timeFrame: 12 months post transplantation
measure: Primary non-function
timeFrame: 12 months post transplantation
measure: Number of Participants with prolonged DGF
timeFrame: 14 days post transplantation
measure: Number of Participants with functional DGF
timeFrame: First 7 days post-transplantation
measure: Duration of dialysis sessions (hours)
timeFrame: First 30- and 90-days post-transplantation
measure: Number of dialysis sessions
timeFrame: First 30- and 90-days post-transplantation
measure: Changes in Quality of Life
timeFrame: 12 months post transplantation
measure: Incidence of de novo Human Leukocyte Antigen (HLA) antibodies within 12 months
timeFrame: 12 months post transplantation
measure: Incidence of biopsy-proven allograft rejection within 12 months
timeFrame: 12 months post transplantation
measure: Tubular cell injury assessed by exploratory urinary biomarkers
timeFrame: 12 months post transplantation
Other outcomes:
Locations:
Study officials:
affiliation: iCoat Medical
name: Ingegerd Dalfelt
role: STUDY_CHAIR
References: