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

Kidney Transplant; Complications Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05246618
• Other study ID #: ATMIRe
• Status: Active, not recruiting
• Phase: Phase 1/Phase 2
• Start date: March 31, 2022
• Est. completion date: May 31, 2024

Study information

• Verified date: November 2023
• Source: iCoat Medical AB
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: May 31, 2024
• Est. primary completion date: July 31, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Ischemia
• Ischemia-reperfusion Injury
• Kidney Transplant; Complications
• Reperfusion Injury
• Wounds and Injuries

Intervention

Drug:
• TUM012
Ex-vivo infusion
• Placebo
Ex-vivo infusion

Locations

Country	Name	City	State
Sweden	Skane University Hospital	Malmö

Sponsors (3)

Lead Sponsor	Collaborator
iCoat Medical AB	CTC Clinical Trial Consultants AB, Region Skane

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Patient survival	Number	One year from randomization
Other	Incidence of graft rejection	Number	One year from randomization
Other	Graft survival	Number	One year from randomization
Primary	Adverse Events	Number of patients with confirmed IMP-related events	Three months from randomization
Primary	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
Primary	12-lead Electro-Cardiogram (Standard of Care Safety)	Assessment: "normal", "abnormal, not clinically significant", or "abnormal, clinically significant"	Three months from randomization
Primary	Systolic/diastolic BP (Standard of Care Safety)	Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"	Three months from randomization
Primary	Pulse Rate (Standard of Care Safety)	Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"	Three months from randomization
Primary	Peripheral blood oxygenation (Standard of Care Safety)	Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"	Three months from randomization
Primary	Body temperature (Standard of Care Safety)	Assessment: "normal", "abnormal, not clinically significant", or "abnormal clinically significant"	Three months from randomization
Secondary	Exploratory histological evaluation of kidney graft	Biopsy	Three months from randomization
Secondary	Exploratory kidney graft function	Number	Three months from randomization
Secondary	Exploratory Efficacy: Proteomics	Changed levels from baseline.	Three months from randomization
Secondary	Exploratory Efficacy: Markers of IR injury and thromboinflammation plasma level	Changed levels from baseline.	Three months from randomization
Secondary	Exploratory Efficacy: Cytokine release plasma level	Changed levels from baseline.	Three months from randomization
Secondary	Exploratory Efficacy: Immune cell graft recruitment plasma level	Changed levels from baseline.	Three months from randomization
Secondary	Exploratory Efficacy: Pharmacokinetics plasma concentration	Changed levels from baseline.	Three months from randomization