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

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Ischemia-reperfusion Injury; Kidney Transplant; Complications
• Intervention / Treatment: Drug: TUM012; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Estimated): 18
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Sweden
  • Malmö, Sweden, SE-205 02
    • Skane University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TUM012; Ex-vivo infusion	Drug: TUM012; Ex-vivo infusion; Other Names: Ex-vivo infusion
Placebo Comparator: Placebo; Ex-vivo infusion	Drug: Placebo; Ex-vivo infusion; Other Names: Ex-vivo infusion

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient survival	Number	One year from randomization
Incidence of graft rejection	Number	One year from randomization
Graft survival	Number	One year from randomization

Collaborators and Investigators

• Sponsor: iCoat Medical AB
• Collaborators: Region Skane; CTC Clinical Trial Consultants AB
• Investigators: Study Director: Ingegerd Dalfelt, iCoat Medical AB

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2022
• Primary Completion (Actual): July 31, 2023
• Study Completion (Estimated): May 31, 2024

Study Registration Dates

• First Submitted: November 28, 2021
• First Submitted That Met QC Criteria: February 15, 2022
• First Posted (Actual): February 18, 2022

Study Record Updates

• Last Update Posted (Actual): December 5, 2023
• Last Update Submitted That Met QC Criteria: November 29, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Ex-vivo kidney allograft treatment; Transplant outcome
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Postoperative Complications; Ischemia; Wounds and Injuries; Reperfusion Injury
• Other Study ID Numbers: ATMIRe

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