Allogeneic peripheral blood mononuclear cells incubated in vitro with mitomycin C for Living donor kidney transplantation | Kidney transplant

Inclusion criteria

• {"criterion_text":"- Donors: 1. Age ≥18 years and able to consent\n- Patients: 7. Negative CDC crossmatch with the donor\n- Patients: 8. Negative PCR test result for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) at Screening\n- Patients: 9. Patient's living donor gave written consent for trial participation\n- Patients: 10. Ability to understand the nature and scope of the clinical trial\n- Patients: 11. Written informed consent given prior to any trial-related procedures\n- Patients: 12. Female patients of childbearing potential must: a. have a negative pregnancy test (blood) at Screening. b. either commit to true abstinence from heterosexual contact or agree to use, and be able to comply with, 2 highly effective measures of contraception control (failure rate less than 1% per year when used consistently and correctly) without interruption, during the trial participation. Patients who discontinue mycophenolic acid derivate during the trial participation can switch to 1 highly effective contraceptive method 6 weeks after the end of mycophenolic acid derivative treatment. Reliable methods for this trial are: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable), intrauterine device, intrauterine hormone-releasing system, bilateral tubal occlusion, sexual abstinence or vasectomized sexual partner. Abstinence from heterosexual contact is only accepted as true abstinence: when this is in line with the preferred and usual lifestyle of the patient. (Periodic abstinence [e.g., calendar, ovulation, symptothermal, post-ovulation methods and withdrawal] is not an acceptable method of contraception.) Postmenopausal (no menses for at least 1 year without alternative medical cause) or surgically sterile female patients (tubal ligation, hysterectomy or bilateral oophorectomy) may be enrolled. c. agree to abstain from breast feeding during the trial participation.\n- Patients: 13. Male patients must practice true abstinence or agree to use a condom during sexual contact with a pregnant woman or a woman of childbearing potential during the trial participation and for at least 90 days after the end of trial participationmycophenolic acid derivative treatment, even if he has undergone a successful vasectomy.\n- Donors: 2. Ability to understand the nature and scope of the clinical trial\n- Donors: 3. Written consent form given prior to any trial-related procedures (including PBMC donation)\n- Patients: 1. Patient with CKD in stage 5 (e.g., estimated glomerular filtration rate [GFR] <15mL/min and/or on renal replacement therapy), who are in preparation for kidney transplantation from a live donor\n- Patients: 2. Age ≥18 years, <75 years\n- Patients: 3. ABO-blood group identical or compatible with donor\n- Patients: 4. First kidney transplantation\n- Patients: 5. Complement dependent cytotoxicity (CDC)-panel reactive antibodies <20%\n- Patients: 6. No detection of a donor-specific HLA-antibody in the Luminex-Assay (cutoff: mean fluorescence intensity [MFI] ≤1,000)"}

Exclusion criteria

• {"criterion_text":"- Donors: 1. Pregnant or breastfeeding\n- Donors: 18. Unexplained night sweats, unexplained fever, unexplained weight loss, prolonged unexplained cough or diarrhea, unexplained skin lesions, lymph gland swelling or thrush\n- Donors: 19. Dura mater and/or cornea grafts, allogeneic organ transplants, xenotransplants, pituitary hormones of human origin received\n- Donors: 2. Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study\n- Donors: 20. Stay of longer than 6 months in the United Kingdom between 1980 and 1996 and/or an operation and/or blood transfusion in the United Kingdom after 01-Jan 1980\n- Donors: 21. Operations or other invasive interventions (e.g., endoscopies, biopsies, catheter applications, acupunctures [except acupuncture with sterile and/or disposable needles]) within 4 months prior to Screening\n- Donors: 22. Any invasive exposure to blood (i.e., allogeneic blood components or plasma derivatives) or blood-contaminated injection needles or instruments, tattoos or piercings within 4 months prior to Screening\n- Donors: 23. Positive PCR test result for SARS-CoV-2 at Screening\n- Donors: 24. Hemoglobin <8.0 g/dL, thrombocytes <80,000/µL and/or leukocytes <3,000/µL\n- Donors: 25. Known history of hypersensitivity to components used in the leukapheresis setting (i.e., components of the anticoagulant acid citrate dextrose solution)\n- Donors: 26. Any finding or medical condition prohibiting the inclusion in the trial according to the judgment of the responsible leukapheresis physician (including assessment of the suitability of the veins for leukapheresis by the investigator)\n- Donors: 10. Active bacterial, mycotic or viral infection, except active infections that, in the investigator’s opinion, do not affect patient safety (e.g., foot fungus, nail fungus, or common warts)\n- Patients: 1. Preexisting severe psychiatric disorder\n- Patients: 2. Heart insufficiency of grade NYHA III or IV\n- Patients: 3. Severe liver disease (aspartate aminotransferase or alanine aminotransferase or gamma glutamyl transpeptidase ≥3 x ULN)\n- Donors: 3. Severe psychiatric disease\n- Patients: 4. Active infection of HIV, HBV, HCV, EBV, or syphilis\n- Patients: 5. Active bacterial, mycotic, or viral infection, except active infections that, in the investigator’s opinion, do not affect patient safety (e.g., foot fungus, nail fungus, or common warts)\n- Patients: 6. Negative serological test result for antibodies specific for Epstein-Barr virus (EBV) antigens (Note: EBV negative patients can be included if the donor is confirmed EBV negative)\n- Patients: 7. Malignant disease within 2 years prior to Screening, except basal cell carcinomas of the skin and in situ carcinomas\n- Patients: 8. Immunosuppressive therapy (e.g., for the treatment of an auto-immune disease) within 6 months prior Screening\n- Patients: 9. Preexisting vasculitis or collagenosis\n- Donors: 11. Known malaria infection; known infection of tuberculosis, Q fever, Salmonella typhi and paratyphi, or osteomyelitis (if not medically documented to have been cured for 2 years); known toxoplasmosis (except if symptom free for 6 months); after completion of treatment for rheumatic fever (except if treatment was completed for 2 years)\n- Patients: 10. Known presence of irregular antibodies in Coombs test\n- Patients: 11. Vaccination within 4 weeks prior to Screening\n- Patients: 12. Spleen removed\n- Patients: 13. Known or suspected abuse of alcohol, drugs, or medicinal products\n- Donors: 4. Severe cardiovascular diseases (i.e., heart insufficiency of grade NYHA III or IV)\n- Donors: 5. Severe neurological diseases\n- Donors: 6. Severe liver or kidney diseases\n- Donors: 7. Any acute or chronic disease that may put the donor at risk in case of cell donation by leukapheresis\n- Donors: 8. Malignant neoplasms, except in situ carcinoma after complete removal\n- Donors: 9. Known infections or exposures to human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), hepatitis E virus, West Nile virus (WNV; testing only required during WNV season [June 1st to November 30th of a year]), gonorrhea or syphilis, with the risk of transmission of infection\n- Donors: 13. Known protozoonosis (babesiosis, trypanosomiasis [e.g., chagas], leishmaniosis), known chronic bacterial infections as brucellosis, rickettsiosis, leprosy, relapsing fever, melioidosis, tularemia (except after assured healing according to documented medical assessment)\n- Donors: 14. Autoimmune diseases requiring systemic immunosuppressive therapy\n- Donors: 15. Allergies requiring systemic immunosuppressive therapy\n- Donors: 16. Immunosuppressive therapy within 6 months prior screening\n- Donors: 17. Known or suspected abuse of alcohol, drugs, or medicinal products"}

Primary endpoints

• {"endpoint_text":"- Proportion of patients who achieve an operational tolerance-like phenotype defined on Visit Day 367 as fulfilling all of the following criteria: 1. No acute rejection, graft loss, graft dysfunction or death; 2. No development of donor-specific HLA antibodies until Visit Day 367; 3. Induction of Breg ≥3% measured on Visit Day 367; 4. Patient on tacrolimus therapy with ≤720 mg ECMPS and no corticosteroids on Visit Day 277 and remaining on this therapy until Visit Day 367.","definition_or_measurement_approach":"Defined at Visit Day 367 by fulfilling all listed criteria: absence of acute rejection/graft loss/graft dysfunction/death; no development of donor-specific HLA antibodies until Day 367 (measured by Luminex single antigen test as per secondary endpoint definitions); induction of Breg ≥3% measured on Visit Day 367; assessment of immunosuppressive regimen (tacrolimus with ≤720 mg EC-MPS and no corticosteroids) at Visit Day 277 and maintained until Day 367."}

Secondary endpoints

• {"endpoint_text":"- Key secondary: Number of patient-relevant infections during the first year after transplantation\n- Key secondary: Proportion of patients with acute rejection (biopsy-proven as >Banff Borderline or clinically suspected rejection according to evaluation of adjudication committee), graft loss, graft dysfunction or death on Visit Day 367\n- AEs including serious AEs and AEs of special interest\n- Frequency of local or systemic reactions as result of MIC application\n- Patient-, graft and death-censored graft survival\n- Incidence of biopsy-proven acute rejections and time to first rejection (>Banff Borderline) according to current version Banff criteria and confirmed by a blinded central pathologist\n- Molecular scores in molecular microscope diagnostic system (MMDx) reading on Visit Day 367\n- Percentage of patients who achieved tacrolimus and EC-MPS dual therapy (MIC Arm A, Control Arm) or tacrolimus monotherapy (MIC Arm B) on Visit Day 367\n- Development of donor-specific HLA-antibodies (>1,000 MFI; confirmed by second measurement after 4 weeks for assessments after Day 6) until Visit Days 6, 187 and 367, as measured by Luminex single antigen test\n- Occurrence of delayed function of the kidney graft after transplantation, defined as dialysis within the first week after transplantation, except for one dialysis for hyperkalemia\n- eGFR (according to chronic kidney disease epidemiology collaboration [CKD-EPI])\n- Incidence of CMV reactivation (CMV-DNA ≥1,000 copies/mL)\n- Incidence of BK virus replication ≥1,000 copies/mL\n- Incidence of BK virus associated nephropathy\n- Incidence of hospital readmissions after transplant surgery\n- Days in hospital, on intensive care (ICU)/intermediate care (IMC) and hours on mechanical ventilation upon re-admission\n- Change of quality of life (SF-36) on Visit Day 367 compared to Baseline\n- Incidence of new-onset diabetes mellitus after transplantation (fasting plasma glucose ≥7.0 mmol/L / 126 mg/dL with no calorie intake for at least 8 hours)\n- Therapeutic intensity score and blood pressure on Visit Day 367 compared to Baseline\n- Breg percentage\n- Anti-donor T cell response to the donor\n- Cumulative steroid dose until Visit Day 367","definition_or_measurement_approach":"Measurements and timepoints provided where specified: infections counted during first year post-transplant; acute rejection defined as biopsy-proven >Banff Borderline or clinically suspected per adjudication committee; AE/SAE reporting per safety monitoring; local/systemic reactions following MIC application; MMDx molecular scores on Visit Day 367; tacrolimus/EC-MPS therapy status assessed on Visit Day 367 (and tacrolimus/EC-MPS dosing evaluated including EC-MPS ≤720 mg at Visit Day 277 as in primary endpoint); donor-specific HLA-antibodies measured by Luminex single antigen test (>1,000 MFI, confirmation by repeat measurement after 4 weeks for assessments after Day 6) at Visit Days 6, 187 and 367; delayed graft function defined as dialysis within first week except one dialysis for hyperkalemia; eGFR by CKD-EPI; CMV and BK virus thresholds defined (≥1,000 copies/mL); QoL via SF-36 change from baseline to Visit Day 367; new-onset diabetes mellitus defined by fasting plasma glucose ≥7.0 mmol/L (126 mg/dL) with ≥8h fasting; multiple other endpoints assessed at specified visits up to Day 367."}

Methods

• Site-based recruitment at participating transplant centers (listed study sites across Germany).
• Use of recruitment materials: recruitment arrangements document (K1_Recruitment arrangements), recruitment video (K2_Recruitment material_Filmscript recruitment video), and flyer/brochure (K2_Recruitment material_Flyer-Brochure) as indicated in trial documents.

Germany

Earliest CTIS Part Ii Submission Date

11-07-2024

Latest Decision Or Authorization Date

12-03-2026

Processing Time Days

609

Number Of Sites

8

Number Of Participants

126

Primary sponsor

Full Name

TolerogenixX GmbH

Organisation Type

Pharmaceutical company

Country Of Registered Address

Germany

Contract research organisations

Name

FGK Clinical Research GmbH

Responsibilities

Multiple sponsor duties (codes: 947661, 947662, 947663, 947664, 947665, 947666, 947667, 947668); contact ractis@fgk-cro.com

Name

Viedoc Technologies AB

Responsibilities

IVRS – treatment randomisation; electronic data capture / randomisation services (contact info: info_se@viedoc.com)

Third parties

• {"country":"Germany","full_name":"FGK Clinical Research GmbH","duties_or_roles":"Sponsor duties codes: 947661, 947662, 947663, 947664, 947665, 947666, 947667, 947668","organisation_type":"Pharmaceutical company"}
• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg; Institut für Immunologie, Abt. Transplantationsimmunologie","duties_or_roles":"Extended immunological monitoring","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Medizinische Klinik Innere Medizin X, Nephrologie - Nierenzentrum, Universitätsklinikum Heidelberg","duties_or_roles":"Genomic and proteomic analysis","organisation_type":"Health care"}
• {"country":"Canada","full_name":"ATAGC - Alberta Transplant Applied Genomics Centre, Transcriptome Science Inc.; Univ of Alberta","duties_or_roles":"MMDx molecular microarray biopsy analysis","organisation_type":"Health care / Academic"}
• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR","duties_or_roles":"Hygieneinstitut Virologie: SARS-CoV-2 testing; other duties (code 4)","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Universitaetsklinik Heidelberg, Zentrallabor","duties_or_roles":"Laboratory services (code 4)","organisation_type":"Health care"}
• {"country":"Germany","full_name":"Universitaetsklinikum Heidelberg AöR (pathology)","duties_or_roles":"Institut für Pathologie; Histopathology","organisation_type":"Hospital/Clinic/Other health care facility"}
• {"country":"Germany","full_name":"Institut für Klinische Transfusionsmedizin und Zelltherapie Heidelberg gGmbH","duties_or_roles":"Donor specific serology/virology testing","organisation_type":"Health care"}
• {"country":"Sweden","full_name":"Viedoc Technologies AB","duties_or_roles":"IVRS – treatment randomisation; other data capture/randomisation duties (codes 947658, 947659 / code 7)","organisation_type":"Non-Pharmaceutical company (vendor)"}
• {"country":"Austria","full_name":"VIETAC - Vienna Transplant and Complement Laboratories; Medical University of Vienna","duties_or_roles":"Torque Teno virus level analysis","organisation_type":"Health care / Academic"}