FIH Phase I/IIa Trial Evaluating Safety of TUM012 to Minimize Ischemic Reperfusion Injury in Kidney Transplantation

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Ischemia-reperfusion Injury, Kidney Transplant; Complications

Intervention / Treatment
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* Drug: TUM012
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TUM012<br>Ex-vivo infusion | Drug: TUM012<br>* Ex-vivo infusion<br>* Other names: Ex-vivo infusion;|
| Placebo Comparator: Placebo<br>Ex-vivo infusion | Drug: Placebo<br>* Ex-vivo infusion<br>* Other names: Ex-vivo infusion;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse Events | Number of patients with confirmed IMP-related events | Three months from randomization | 
| Laboratory Analyses (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal, clinically significant, will as appropriate be reported as Adverse Events. | Three months from randomization | 
| 12-lead Electro-Cardiogram (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal, clinically significant | Three months from randomization | 
| Systolic/diastolic BP (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal clinically significant | Three months from randomization | 
| Pulse Rate (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal clinically significant | Three months from randomization | 
| Peripheral blood oxygenation (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal clinically significant | Three months from randomization | 
| Body temperature (Standard of Care Safety) | Assessment: normal, abnormal, not clinically significant, or abnormal clinically significant | Three months from randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploratory histological evaluation of kidney graft | Biopsy | Three months from randomization | 
| Exploratory kidney graft function | Number | Three months from randomization | 
| Exploratory Efficacy: Proteomics | Changed levels from baseline. | Three months from randomization | 
| Exploratory Efficacy: Markers of IR injury and thromboinflammation plasma level | Changed levels from baseline. | Three months from randomization | 
| Exploratory Efficacy: Cytokine release plasma level | Changed levels from baseline. | Three months from randomization | 
| Exploratory Efficacy: Immune cell graft recruitment plasma level | Changed levels from baseline. | Three months from randomization | 
| Exploratory Efficacy: Pharmacokinetics plasma concentration | Changed levels from baseline. | Three months from randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ex-vivo kidney allograft treatment, Transplant outcome