Clinical Trial With Donor Modified Immune Cells in Living Donor Kidney Transplantation

NCT ID: NCT05365672

Last Updated: 2025-04-11

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 126 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-04
• Study Completion Date: 2028-12-31

Brief Summary

In this clinical trial the investigational medicinal product MIC is to be examined for its efficacy and safety in patients with living kidney transplantation. For this purpose the patients participating in the clinical trial and their associated kidney donors are randomly assigned to one of three treatment groups during the screening procedure. For the production of the investigational medicinal product MIC for the patients in the MIC therapy group mononuclear cells of the peripheral blood are obtained from the donors in a leukapheresis procedure. In the subsequent treatment phase, the patients in the MIC therapy group receive MIC as a weight-adjusted single dose administered intravenously. As part of the 12-month follow-up phase the kidney transplant and the corresponding immunosuppressive therapy will take place seven days later. Patients in the control group will receive a conventional standard immunosuppressive regimen without prior administration of the investigational medicinal product MIC after kidney transplantation. All patients taking part in this clinical trial are followed up for one year after kidney transplantation with regard to the efficacy and safety of MIC in regular visits at their study site. As the investigational medicinal product is an advanced therapy medicinal product (ATMP) all subjects will be monitored for a further 2 years after the end of the follow-up phase of the clinical trial.

A total of 63 transplant pairs, consisting of donor and transplant recipient, are to be included in the clinical trial. The 63 patients will be randomized 2:1 to be treated with MIC (MIC group) or without MIC (control group). Additionally, low immunosuppression or minimal immunosuppression treatments will be used in the patients in the MIC group.

Conditions

Kidney Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

MIC with low immunosuppression

Patients in MIC Arm A receive the investigational medicinal product MIC plus immunosuppression consisting of tacrolimus, mycophenolic acid derivative and corticosteroids (without IL-2 receptor antibody induction therapy).

Tacrolimus dose will be gradually reduced to 4-8 μg/L at Day 183 and the corticosteroid treatment will be stopped at Day 92 after gradual dose reduction.

Group Type: EXPERIMENTAL

MIC

Intervention Type: BIOLOGICAL

Single intravenous infusion of 1.5x10exp8 MIC per kg of body weight

MIC with minimal immunosuppression

Patients in MIC Arm B receive the investigational medicinal product MIC plus immunosuppression consisting of tacrolimus, mycophenolic acid derivative and corticosteroids (without IL-2 receptor antibody induction therapy).

Tacrolimus dose will be gradually reduced to 4-8 μg/L at Day 183 and the corticosteroid treatment will be stopped at Day 92 after gradual dose reduction.

The mycophenolic acid derivative will be stopped between Days 141 and 182.

Group Type: EXPERIMENTAL

MIC

Intervention Type: BIOLOGICAL

Single intravenous infusion of 1.5x10exp8 MIC per kg of body weight

Standard of care immunosuppression for transplantation

Patients of the Control Arm receive standard of care immunosuppression for kidney transplantations according to the Efficacy Limiting Toxicity Elimination (ELITE) symphony scheme (interleukin \[IL\]-2 receptor antibody induction therapy, tacrolimus, mycophenolic acid derivative and corticosteroids) without the investigational medicinal product MIC.

Group Type: OTHER

Standard of Care

Intervention Type: OTHER

No application of the investigational medicinal product MIC

Interventions

MIC

Single intravenous infusion of 1.5x10exp8 MIC per kg of body weight

Intervention Type: BIOLOGICAL

Standard of Care

No application of the investigational medicinal product MIC

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Donors:

1. Age ≥18 years and able to consent

2. Ability to understand the nature and scope of the clinical trial

3. Written consent form given prior to any trial-related procedures (including PBMC donation)

Patients:

1. Patient with CKD in stage 5 (e.g., estimated glomerular filtration rate [eGFR] <15 mL/min and/or on renal replacement therapy), who are in preparation for kidney transplantation from a live donor

2. Age ≥18 years, <70 years

3. ABO-blood group identical or compatible with donor

4. First kidney transplantation

5. Complement dependent cytotoxicity (CDC)-panel reactive antibodies <20%

6. No detection of a donor-specific HLA-antibody in the Luminex-Assay (cutoff: mean fluorescence intensity [MFI] ≤1,000)

7. Negative CDC crossmatch with the donor

8. Negative PCR test result for severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) at Screening

9. Patient's living donor gave written consent for trial participation

10. Ability to understand the nature and scope of the clinical trial

11. Written informed consent given prior to any trial-related procedures

12. Female patients of childbearing potential must:

1. have a negative pregnancy test (blood) at Screening.

2. 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.

3. agree to abstain from breast feeding during the trial participation.

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 mycophenolic acid derivative treatment, even if he has undergone a successful vasectomy.

Exclusion Criteria

Donors:

1. Pregnant or breastfeeding

2. Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study

3. Severe psychiatric disease

4. Severe cardiovascular diseases (i.e., heart insufficiency of grade NYHA III or IV)

5. Severe neurological diseases

6. Severe liver or kidney diseases

7. Any acute or chronic disease that may put the donor at risk in case of cell donation by leukapheresis

8. Malignant neoplasms, except in situ carcinoma after complete removal

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 (Note: If tested positive for EBV immunoglobulin [Ig]M, an EBV PCR test has to be performed for confirmation)

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)

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)

12. Known transmissible spongiform encephalopathies

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)

14. Autoimmune diseases requiring systemic immunosuppressive therapy

15. Allergies requiring systemic immunosuppressive therapy

16. Immunosuppressive therapy within 6 months prior screening

17. Known or suspected abuse of alcohol, drugs, or medicinal products

18. Unexplained night sweats, unexplained fever, unexplained weight loss, prolonged unexplained cough or diarrhea, unexplained skin lesions, lymph gland swelling or thrush

19. Dura mater and/or cornea grafts, allogeneic organ transplants, xenotransplants, pituitary hormones of human origin received

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

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

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

23. Positive PCR test result for SARS-CoV-2 at Screening

24. Hemoglobin <8.0 g/dL, thrombocytes <80,000/μL and/or leukocytes <3,000/μL

25. Known history of hypersensitivity to components used in the leukapheresis setting (i.e., components of the anticoagulant acid citrate dextrose solution)

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)

Patients:

1. Preexisting severe psychiatric disorder

2. Heart insufficiency of grade NYHA III or IV

3. Severe liver disease (aspartate aminotransferase or alanine aminotransferase or gamma glutamyl transpeptidase ≥3 x ULN)

4. Active infection of HIV, HBV, HCV, EBV or syphilis

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)

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)

7. Malignant disease within 2 years prior to Screening, except basal cell carcinomas of the skin and in situ carcinomas

8. Immunosuppressive therapy (e.g., for the treatment of an auto-immune disease) within 6 months prior Screening

9. Preexisting vasculitis or collagenosis

10. Known presence of irregular antibodies in Coombs test

11. Vaccination within 4 weeks prior to Screening

12. Spleen removed

13. Known or suspected abuse of alcohol, drugs, or medicinal products

14. Pregnant or breastfeeding

15. Female patients who have a child with the donor or were pregnant from the donor due to possible sensitization

16. Known history of hypersensitivity to the cellular components or to any other constituent/excipient in the pharmaceutical formulation of MIC (e.g., components of the SSP+ buffer as electrolytes (sodium chloride, potassium chloride, magnesium), citrate and phosphate, traces of mitomycin C, human albumin, or EDTA)

17. Any finding or medical condition prohibiting the inclusion in the trial according to the judgment of the investigator

18. Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study

19. Employees of the sponsor, or employees or relatives of the investigator

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 69 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

FGK Clinical Research GmbH

INDUSTRY

Sponsor Role: collaborator

TolerogenixX GmbH

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian Morath, Prof.Dr.med.

Role: PRINCIPAL_INVESTIGATOR

University Hospital Heidelberg

Locations

Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charité - Universitätsmedizin Berlin

Berlin, , Germany

Site Status: NOT_YET_RECRUITING

Universitätsklinikum Hamburg-Eppendorf, Universitäres Transplantations Centrum

Hamburg, , Germany

Site Status: RECRUITING

Innere Medizin V; Klinik für Hämatologie, Onkologie, Rheumatologie; Universitätsklinikum Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Medizinische Klinik, Innere Medizin X Nephrologie - Nierenzentrum Universitätsklinikum Heidelberg

Heidelberg, , Germany

Site Status: RECRUITING

Transplantationszentrum München; Ludwig-Maximilians-Universität

Munich, , Germany

Site Status: RECRUITING

Klinikum rechts der Isar, Abteilung Nephrologie, Technische Universität München

Munich, , Germany

Site Status: NOT_YET_RECRUITING

Universitätsklinikum Münster, Transplantationsnephrologie

Münster, , Germany

Site Status: RECRUITING

Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen; Transplantationszentrum Stuttgart

Stuttgart, , Germany

Site Status: RECRUITING

Countries

Germany

Central Contacts

Matthias Schaier, Prof.Dr.med.

Role: CONTACT

schaier@tolerogenixx.com

+49 162 2638 005

References

Morath C, Schmitt A, Schmitt M, Wang L, Kleist C, Opelz G, Susal C, Tran TH, Scherer S, Schwenger V, Kemmner S, Fischereder M, Stangl M, Hauser IA, Sommerer C, Nusshag C, Kalble F, Speer C, Benning L, Bischofs C, Sauer S, Schubert ML, Kunz A, Huckelhoven-Krauss A, Neuber B, Mehrabi A, Schwab C, Waldherr R, Sander A, Busch C, Czock D, Bohmig GA, Reiser J, Roers A, Muller-Tidow C, Terness P, Zeier M, Daniel V, Schaier M. Individualised immunosuppression with intravenously administered donor-derived modified immune cells compared with standard of care in living donor kidney transplantation (TOL-2 Study): protocol for a multicentre, open-label, phase II, randomised controlled trial. BMJ Open. 2022 Nov 11;12(11):e066128. doi: 10.1136/bmjopen-2022-066128.

Reference Type: DERIVED

PMID: 36368749 (View on PubMed)

Other Identifiers

TOL-2

Identifier Type: -

Identifier Source: org_study_id