Clinical trial NCT05246618: FIH Phase I/IIa Trial Evaluating Safety of TUM012 to Minimize Ischemic Reperfusion Injury in Kidney Transplantation
Official title: Phase I FIH Phase I/IIa Randomized Placebocontrolled Doubleblind Trial Evaluating Safety and Tolerability of ExVivo Deceased Donor Kidney Allograft Treatment With TUM012 to Minimize Ischemic Reperfusion Injury After Kidney Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ischemia-reperfusion Injury
Kidney Transplant; Complications
Keywords: Ex-vivo kidney allograft treatment
Transplant outcome
Lead sponsor: iCoat Medical AB
Sponsor class: INDUSTRY
Collaborators: name: CTC Clinical Trial Consultants AB
name: Region Skane
First posted: 2022-02-18
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: A first-in-human single center, randomized, double-blind, placebo-controlled trial, with primary objective to evaluate safety and tolerability of ex-vivo kidney allograft treatment with TUM012 to reduce ischemia-reperfusion injury in de novo kidney transplant recipients.

Detailed description: Graft ischemia and reperfusion related injury is still the leading cause of graft failure in Deceased Donor kidney transplantation. The aim of the trial is to evaluate the safety of ex-vivo treatment of kidney allografts from deceased-donors with TUM012 to diminish ischemia reperfusion related inflammation, and improve overall transplantat outcome.

Eligibility criteria: Inclusion Criteria:

* Standard and extended criteria donor ≥18 years of age, suitable for clinical transplantation and preserved by cold storage.
* Available, personally signed and dated Informed Consent Form (ICF)
* Male or female Chronic Kidney Disease (CKD) patient ≥18 years of age, with Glomerular Filtration Rate (GFR) ≤15 mL/min, awaiting their first kidney transplantation
* ABO-compatible, negative pre-transplant CDC class I and II crossmatch with no Donor Specific Antibodies (DSA), defined as ≤1 000 Mean Fluorescent Intensity (MFI).
* Patient is suitable for surgery, as judged by the investigator
* Completed vaccination program for pneumococcal disease, varicella zoster, measles, and SARS-CoV-2 virus

Exclusion Criteria:

* Surgically induced injuries compromising ex-vivo treatment and/or transplant outcome, as judged by the transplantation surgeon
* Previously undergone any organ and/or cell transplantations
* Patients with positive CDC class I and/or II crossmatch, or negative CDC class I and II crossmatch with pre-existing DSA \> 1,000 MFI
* ABO-incompatible DD KT
* Pregnant or breast-feeding woman
* Woman of child-bearing potential, unwilling to use an adequate contraceptive method
* Prior participation in clinical trial with (approved or non-approved) IMP within one month prior to screening for this trial.
* Prior malignancy diagnosis ≤5 years, except for adequately treated basal cell, or squamous cell skin cancer, and cervical carcinoma in situ
* Positive result for serum Human Immunodeficiency Virus (HIV), active hepatitis B-, or C-infection in pre-transplant evaluation
* Clinical signs of ongoing infectious disease, defined as C-Reactive Protein (CRP) \>10, unless stable since \>4 weeks (\<50% increase)
* Concomitant severe conditions requiring treatment and close monitoring, e.g., cardiac failure \>grade 3 New York Heart Association (NYHA), unstable coronary disease, or oxygen dependent Chronic Obstructive Pulmonary Disease (COPD)
* 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
* Patient unlikely to comply with trial procedures, restrictions, and requirements (e.g., caused by substance abuse, concurrent medical condition, etc.), as judged by investigator

Primary outcomes:
measure: Adverse Events
timeFrame: Three months from randomization
measure: Laboratory Analyses (Standard of Care Safety)
timeFrame: Three months from randomization
measure: 12-lead Electro-Cardiogram (Standard of Care Safety)
timeFrame: Three months from randomization
measure: Systolic/diastolic BP (Standard of Care Safety)
timeFrame: Three months from randomization
measure: Pulse Rate (Standard of Care Safety)
timeFrame: Three months from randomization
measure: Peripheral blood oxygenation (Standard of Care Safety)
timeFrame: Three months from randomization
measure: Body temperature (Standard of Care Safety)
timeFrame: Three months from randomization
Secondary outcomes:
measure: Exploratory histological evaluation of kidney graft
timeFrame: Three months from randomization
measure: Exploratory kidney graft function
timeFrame: Three months from randomization
measure: Exploratory Efficacy: Proteomics
timeFrame: Three months from randomization
measure: Exploratory Efficacy: Markers of IR injury and thromboinflammation plasma level
timeFrame: Three months from randomization
measure: Exploratory Efficacy: Cytokine release plasma level
timeFrame: Three months from randomization
measure: Exploratory Efficacy: Immune cell graft recruitment plasma level
timeFrame: Three months from randomization
measure: Exploratory Efficacy: Pharmacokinetics plasma concentration
timeFrame: Three months from randomization
Other outcomes:
measure: Patient survival
timeFrame: One year from randomization
measure: Incidence of graft rejection
timeFrame: One year from randomization
measure: Graft survival
timeFrame: One year from randomization
Locations:
city: Malmö
country: Sweden
facility: Skane University Hospital
Study officials:
affiliation: iCoat Medical AB
name: Ingegerd Dalfelt
role: STUDY_DIRECTOR
References: