Kidney TransplantationPhase 2NCT05365672
Clinical Trial With Donor Modified Immune Cells in Living Donor Kidney Transplantation
A Phase 2 study testing MIC in people with Kidney Transplantation, run by TolerogenixX GmbH at 8 sites in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 69 years
- Conditions the study is for
- Kidney Transplantation
- What is being tested?
- MIC
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 126 participants
- Where
- 8 sitesGermany
- Study dates
- 4 May 2022to Dec 2028
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 69 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Donors:
- Age ≥18 years and able to consent
- Ability to understand the nature and scope of the clinical trial
- Written consent form given prior to any trial-related procedures (including PBMC donation)
- Patients:
- 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
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- Age ≥18 years, <70 years
- ABO-blood group identical or compatible with donor
- First kidney transplantation
- Complement dependent cytotoxicity (CDC)-panel reactive antibodies <20%
- No detection of a donor-specific HLA-antibody in the Luminex-Assay (cutoff: mean fluorescence intensity [MFI] ≤1,000)
- Negative CDC crossmatch with the donor
- Negative PCR test result for severe acute respiratory syndrome coronavirus-2 (SARSCoV-2) at Screening
- Patient's living donor gave written consent for trial participation
- Ability to understand the nature and scope of the clinical trial
- Written informed consent given prior to any trial-related procedures
- Female patients of childbearing potential must:
- have a negative pregnancy test (blood) at Screening.
- 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.
- agree to abstain from breast feeding during the trial participation.
- 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.
Who cannot join
- Donors:
- Pregnant or breastfeeding
- Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study
- Severe psychiatric disease
- Severe cardiovascular diseases (i.e., heart insufficiency of grade NYHA III or IV)
- Severe neurological diseases
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- Severe liver or kidney diseases
- Any acute or chronic disease that may put the donor at risk in case of cell donation by leukapheresis
- Malignant neoplasms, except in situ carcinoma after complete removal
- 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)
- 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)
- 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)
- Known transmissible spongiform encephalopathies
- 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)
- Autoimmune diseases requiring systemic immunosuppressive therapy
- Allergies requiring systemic immunosuppressive therapy
- Immunosuppressive therapy within 6 months prior screening
- Known or suspected abuse of alcohol, drugs, or medicinal products
- Unexplained night sweats, unexplained fever, unexplained weight loss, prolonged unexplained cough or diarrhea, unexplained skin lesions, lymph gland swelling or thrush
- Dura mater and/or cornea grafts, allogeneic organ transplants, xenotransplants, pituitary hormones of human origin received
- 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
- 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
- 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
- Positive PCR test result for SARS-CoV-2 at Screening
- Hemoglobin <8.0 g/dL, thrombocytes <80,000/μL and/or leukocytes <3,000/μL
- Known history of hypersensitivity to components used in the leukapheresis setting (i.e., components of the anticoagulant acid citrate dextrose solution)
- 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:
- Preexisting severe psychiatric disorder
- Heart insufficiency of grade NYHA III or IV
- Severe liver disease (aspartate aminotransferase or alanine aminotransferase or gamma glutamyl transpeptidase ≥3 x ULN)
- Active infection of HIV, HBV, HCV, EBV or syphilis
- 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)
- 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)
- Malignant disease within 2 years prior to Screening, except basal cell carcinomas of the skin and in situ carcinomas
- Immunosuppressive therapy (e.g., for the treatment of an auto-immune disease) within 6 months prior Screening
- Preexisting vasculitis or collagenosis
- Known presence of irregular antibodies in Coombs test
- Vaccination within 4 weeks prior to Screening
- Spleen removed
- Known or suspected abuse of alcohol, drugs, or medicinal products
- Pregnant or breastfeeding
- Female patients who have a child with the donor or were pregnant from the donor due to possible sensitization
- 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)
- Any finding or medical condition prohibiting the inclusion in the trial according to the judgment of the investigator
- Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study
- Employees of the sponsor, or employees or relatives of the investigator
Trial locations and contacts
8 sites in 1 country. Contact the study team or a site near you to ask about taking part.
8 sites in 1 country
Germany8 sites, 8 recruiting
- Not yet recruiting
Medizinische Klinik mit Schwerpunkt Nephrologie und Internistische Intensivmedizin Charité - Universitätsmedizin Berlin
Berlin, 13353
- Recruiting
Universitätsklinikum Hamburg-Eppendorf, Universitäres Transplantations Centrum
Hamburg, 20246
- Recruiting
Innere Medizin V; Klinik für Hämatologie, Onkologie, Rheumatologie; Universitätsklinikum Heidelberg
Heidelberg, 69120
- Recruiting
Medizinische Klinik, Innere Medizin X Nephrologie - Nierenzentrum Universitätsklinikum Heidelberg
Heidelberg, 69120
- Recruiting
Transplantationszentrum München; Ludwig-Maximilians-Universität
Munich, 81377
- Not yet recruiting
Klinikum rechts der Isar, Abteilung Nephrologie, Technische Universität München
Munich, 81675
- Recruiting
Universitätsklinikum Münster, Transplantationsnephrologie
Münster, 48149
- Recruiting
Klinik für Nieren-, Hochdruck- und Autoimmunerkrankungen; Transplantationszentrum Stuttgart
Stuttgart, 70174
About this study
Official title: An Open, Randomized-controlled, Multi-center Phase-II Clinical Trial of Individualized Immunosuppression With Intravenously Administered Donor Modified Immune Cells (MIC) Compared to Standard-of-care in Living Donor Kidney Transplantation
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
- Being tested
- MIC, Standard of Care
- Keywords
- living donor kidney transplantation, TOL-2, modified immune cells, MIC, mitomycin C, peripheral blood mononuclear cells, PBMC, kidney donor, TolerogenixX, tolerance, immunosuppression, donor-specific unresponsiveness, EudraCT No. 2021-000561-33
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MICBiological
Single intravenous infusion of 1.5x10exp8 MIC per kg of body weight
Standard of CareOther
No application of the investigational medicinal product MIC
| Study group | Role | What they receive |
|---|---|---|
| MIC with low immunosuppression | Experimental | 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. Receives: Biological: MIC |
| MIC with minimal immunosuppression | Experimental | 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. Receives: Biological: MIC |
| Standard of care immunosuppression for transplantation | Other | 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. Receives: Other: Standard of Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
No acute rejection, graft loss, graft dysfunction
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated:
Criterium 1.: No acute rejection (biopsy-proven as >Banff Borderline or clinically suspected rejection according to evaluation of adjudication committee), graft loss, graft dysfunction (eGFR <30 mL/min), or death on Visit Day 367
Measured: On day 367 post investigational medicinal product application
No development of de novo donor-specific HLA- antibodies
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated:
Criterium 2.: No development of donor-specific HLA antibodies (DSA ≤1,000 MFI; values >1,000 MFI after Visit Day 6 has to be confirmed by second measurement after 4 weeks) until Visit Day 367 as measured by Luminex single antigen test
Measured: Between day 0 and day 367 post investigational medicinal product application
Induction of regulatory B cells (Breg) to ≥3%
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated:
Criterium 3.: Induction of Breg ≥3% measured on Visit Day 367 (patient has to be infection-free at timepoint of measurement)
Measured: On day 367 post investigational medicinal product application
Patient on tacrolimus therapy with ≤720 mg EC-MPS and no corticosteroids
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated:
Criterium 4.: Patient on tacrolimus therapy with ≤720 mg EC-MPS and no corticosteroids (as well as no other immunosuppressive drug) on Visit Day 277 and remaining on this therapy until Visit Day 367
Measured: Between days 277 and 367 post investigational medicinal product application
Secondary outcomes (23)
Key secondary: Number of patient-relevant infections during the first year after transplantation
Safety evaluation of MIC treatment versus standard of care therapy is based on number of patient-relevant infections during the first year after transplantation.
Patient-relevant infections are:
Pneumonia, and/or complicated urinary tract infection, and/or sepsis from any cause, and/or opportunistic infection.
Measured: On day 367 post investigational medicinal product application
Key secondary: Biopsy proven acute rejection, graft loss, graft dysfunction, or death
Safety evaluation of MIC treatment versus standard of care therapy is also based on 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
Measured: On day 367 post investigational medicinal product application
Number of Adverse Events (AEs) including serious AEs and AEs of special interest
Determine safety and efficacy of MIC treatment based on AE outcome
Measured: From screening through study completion, 3 years estimated.
Frequency of local or systemic reactions as result of MIC application
Determine safety and efficacy of MIC treatment based on further parameters other than comparison to standard of care therapy
Measured: From day 0 through study completion, 3 years estimated.
Monitoring of patient survival
Determine safety and efficacy of MIC treatment based on further parameters other than comparison to standard of care therapy: Monitoring for death of patient.
Measured: On Visit Days 187 and 367 post investigational medicinal product application
Monitoring of graft kidney survival
Determine safety and efficacy of MIC treatment based on further parameters other than comparison to standard of care therapy: Monitoring for death of grafted kidney.
Measured: On Visit days 187 and 367 post investigational medicinal product application
Incidence of biopsy-proven acute rejections and time to first rejection (>Banff Borderline)
Assessment is done according to current version Banff criteria and confirmed by a blinded central pathologist
Measured: On Visit Days 97 and 142 post investigational medicinal product application
Molecular scores in molecular microscope diagnostic system (MMDx)
Molecular biopsy analysis using MMDx will be done
Measured: On Visit Day 367 post investigational medicinal product application
Percentage of patients who achieved tacrolimus and EC-MPS dual therapy or tacrolimus monotherapy
Percentage of patients who achieved tacrolimus and EC-MPS dual therapy in the MIC Arm A or Control Arm or tacrolimus monotherapy in the MIC Arm B
Measured: On day 367 post investigational medicinal product application
Amount of donor-specific HLA antibodies (DSA)
DSA measurement (>1,000 MFI; confirmed by second measurement after 4 weeks for assessments after Day 6) will be done by blinded Luminex single antigen test
Measured: On Visit Days 6, 187 and 367 post investigational medicinal product application
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
Measured: On Visit Day 37 post investigational medicinal product application
Assessment of estimated Glomerular Filtration Rate (eGFR) [CKD-EPI])
Measurement of eGFR according to chronic kidney disease epidemiology collaboration (CKD-EPI)
Measured: From screening through study completion, 3 years estimated.
Assessment of the incidence of cytomegalovirus (CMV) reactivation (CMV-DNA ≥1,000 copies/mL)
CMV amount will be measured as CMV-DNA copies/mL
Measured: From screening through study completion, 3 years estimated.
Assessment of the incidence of BK virus replication ≥10,000 copies/mL
BK virus amount will be measured as DNA copies/mL
Measured: From screening through study completion, 3 years estimated.
Assessment of the incidence of BK virus associated nephropathy
Nephropathy will be assessed using biopsy material
Measured: From screening through study completion, 3 years estimated.
Assessment of the incidence of hospital readmissions after transplant surgery
Assessment of the number of patients who had hospital readmissions after transplant surgery
Measured: On days 5, 7, 37, 97, 142, 187, 277, 367, month 24, 36 post investigational medicinal product application
Assessment of days in hospital, on intensive care and hours on mechanical ventilation upon re-admission
Assessment of days in hospital, on intensive care and hours on mechanical ventilation (the treatment to help a person breathe when they find it difficult or are unable to breathe on their own) that patients needed upon hospital re-admission after transplant surgery
Measured: On day -14 to -7 and 367 post investigational medicinal product application
Change in quality of life as assessed by questionnaire
The SF-36 questionnaire with 36 questions will be used to assess the change in quality of life between screening and first year after treatment
Measured: Between day -14 to -7 and 367 post investigational medicinal product application
Incidence of new-onset diabetes mellitus after transplantation
Assessment of incidence of diabetes mellitus after transplantation by measuring fasting plasma glucose (≥7.0 mmol/L / 126 mg/dL) with no calorie intake for at least 8 hours
Measured: From day 0 through study completion, 3 years estimated.
Determination of therapeutic intensity score (TIS) based on blood pressure on Visit Day 367 compared to Baseline
Assessment of the TIS as a summary measure that accounts for the number and the relative doses of blood pressure medications for a patient by a blinded adjudication committee one year after treatment
Measured: On day -14 to -7 and 367 post investigational medicinal product application
Breg percentage
Assessment of the percentage of regulatory B cells of the white blood cell population measured from blood samples by Fluorecscence Activated Cell Sorting (FACS)
Measured: On day 367 post investigational medicinal product application
Anti-donor T cell response to the donor
Anti-donor T cell response will be assessed from blood samples using the mixed lymphocyte reaction in vitro assay
Measured: From day 0 through study completion, 3 years estimated.
Cumulative steroid dose during the first year after treatment
Assessment of the overall amount of steroids given to the patient as immunosuppressive treatment during the first year after transplantation
Measured: On day 367 post investigational medicinal product application
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 May 2022
- Study start4 May 2022
- Primary completionDec 2026 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Kidney TransplantationStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 126 participants (estimated)
Sponsor and investigators
- Lead sponsor
- TolerogenixX GmbH
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Responsible party
- Sponsor
- Investigators
- Christian Morath, Prof.Dr.med., Principal investigator, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05365672
- Sponsor's protocol ID
- TOL-2
- Status last verified
- Apr 2025
- First submitted
- 26 Apr 2022
- Last updated
- 11 Apr 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 36368749
Study at a glance
From the registry record, last updated by the sponsor on 11 Apr 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open, Randomized-controlled, Multi-center Phase-II Clinical Trial of Individualized Immunosuppression With Intravenously Administered Donor Modified Immune Cells (MIC) Compared to Standard-of-care in Living Donor Kidney Transplantation
- ClinicalTrials.gov ID
- NCT05365672
- Acronym / sponsor ID
- TOL-2
- Conditions
- Kidney Transplantation
- Keywords
- living donor kidney transplantation, TOL-2, modified immune cells, MIC, mitomycin C, peripheral blood mononuclear cells, PBMC, kidney donor
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 126 participants (estimated)
- Lead sponsor
- TolerogenixX GmbHIndustry (pharma, biotech, devices)
- Collaborators
- FGK Clinical Research GmbH
- Study start
- 4 May 2022 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 9 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| MIC with low immunosuppression | Experimental | Biological: MICPatients 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. |
| MIC with minimal immunosuppression | Experimental | Biological: MICPatients 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. |
| Standard of care immunosuppression for transplantation | Other | Other: Standard of CarePatients 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. |
Who may qualify
- Ages
- 18 to 69 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Age ≥18 years and able to consent
- Ability to understand the nature and scope of the clinical trial
- Written consent form given prior to any trial-related procedures (including PBMC donation)
- 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
- Age ≥18 years, <70 years
Key exclusion criteria (47 listed)
- Pregnant or breastfeeding
- Participation in an interventional clinical trial within 30 days prior to Screening or in observation period of a competing study
- Severe psychiatric disease
- Severe cardiovascular diseases (i.e., heart insufficiency of grade NYHA III or IV)
- Severe neurological diseases
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MICSingle intravenous infusion of 1.5x10exp8 MIC per kg of body weight | Biological | MIC with low immunosuppression, MIC with minimal immunosuppression |
| Standard of CareNo application of the investigational medicinal product MIC | Other | Standard of care immunosuppression for transplantation |
Primary outcome
No acute rejection, graft loss, graft dysfunction
Time frame: On day 367 post investigational medicinal product application
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated: Criterium 1.: No acute rejection (biopsy-proven as >Banff Borderline or clinically suspected rejection according to evaluation of adjudication committee), graft loss, graft dysfunction (eGFR <30 mL/min), or death on Visit Day 367
No development of de novo donor-specific HLA- antibodies
Time frame: Between day 0 and day 367 post investigational medicinal product application
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated: Criterium 2.: No development of donor-specific HLA antibodies (DSA ≤1,000 MFI; values >1,000 MFI after Visit Day 6 has to be confirmed by second measurement after 4 weeks) until Visit Day 367 as measured by Luminex single antigen test
Induction of regulatory B cells (Breg) to ≥3%
Time frame: On day 367 post investigational medicinal product application
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated: Criterium 3.: Induction of Breg ≥3% measured on Visit Day 367 (patient has to be infection-free at timepoint of measurement)
Patient on tacrolimus therapy with ≤720 mg EC-MPS and no corticosteroids
Time frame: Between days 277 and 367 post investigational medicinal product application
Proportion of patients who achieve an operational tolerance-like phenotype compared to standard of care therapy defined on Visit Day 367 as fulfilling four criteria that are evaluated: Criterium 4.: Patient on tacrolimus therapy with ≤720 mg EC-MPS and no corticosteroids (as well as no other immunosuppressive drug) on Visit Day 277 and remaining on this therapy until Visit Day 367
23 secondary outcomes
Key secondary: Number of patient-relevant infections during the first year after transplantation
Time frame: On day 367 post investigational medicinal product application
Key secondary: Biopsy proven acute rejection, graft loss, graft dysfunction, or death
Time frame: On day 367 post investigational medicinal product application
Number of Adverse Events (AEs) including serious AEs and AEs of special interest
Time frame: From screening through study completion, 3 years estimated.
Frequency of local or systemic reactions as result of MIC application
Time frame: From day 0 through study completion, 3 years estimated.
Monitoring of patient survival
Time frame: On Visit Days 187 and 367 post investigational medicinal product application
Monitoring of graft kidney survival
Time frame: On Visit days 187 and 367 post investigational medicinal product application
Incidence of biopsy-proven acute rejections and time to first rejection (>Banff Borderline)
Time frame: On Visit Days 97 and 142 post investigational medicinal product application
Molecular scores in molecular microscope diagnostic system (MMDx)
Time frame: On Visit Day 367 post investigational medicinal product application
Percentage of patients who achieved tacrolimus and EC-MPS dual therapy or tacrolimus monotherapy
Time frame: On day 367 post investigational medicinal product application
Amount of donor-specific HLA antibodies (DSA)
Time frame: On Visit Days 6, 187 and 367 post investigational medicinal product application
Occurrence of delayed function of the kidney graft after transplantation
Time frame: On Visit Day 37 post investigational medicinal product application
Assessment of estimated Glomerular Filtration Rate (eGFR) [CKD-EPI])
Time frame: From screening through study completion, 3 years estimated.
Assessment of the incidence of cytomegalovirus (CMV) reactivation (CMV-DNA ≥1,000 copies/mL)
Time frame: From screening through study completion, 3 years estimated.
Assessment of the incidence of BK virus replication ≥10,000 copies/mL
Time frame: From screening through study completion, 3 years estimated.
Assessment of the incidence of BK virus associated nephropathy
Time frame: From screening through study completion, 3 years estimated.
Assessment of the incidence of hospital readmissions after transplant surgery
Time frame: On days 5, 7, 37, 97, 142, 187, 277, 367, month 24, 36 post investigational medicinal product application
Assessment of days in hospital, on intensive care and hours on mechanical ventilation upon re-admission
Time frame: On day -14 to -7 and 367 post investigational medicinal product application
Change in quality of life as assessed by questionnaire
Time frame: Between day -14 to -7 and 367 post investigational medicinal product application
Incidence of new-onset diabetes mellitus after transplantation
Time frame: From day 0 through study completion, 3 years estimated.
Determination of therapeutic intensity score (TIS) based on blood pressure on Visit Day 367 compared to Baseline
Time frame: On day -14 to -7 and 367 post investigational medicinal product application
Breg percentage
Time frame: On day 367 post investigational medicinal product application
Anti-donor T cell response to the donor
Time frame: From day 0 through study completion, 3 years estimated.
Cumulative steroid dose during the first year after treatment
Time frame: On day 367 post investigational medicinal product application
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Apr 2025.
- Derived from this study: PubMed 36368749Morath 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Christian Morath, Prof.Dr.med. principal investigator
University Hospital Heidelberg
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing MIC in people with Kidney Transplantation, run by TolerogenixX GmbH at 8 sites in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 21 inclusion and 47 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 11 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Matthias Schaier, Prof.Dr.med. (+49 162 2638 005, schaier@tolerogenixx.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
No acute rejection, graft loss, graft dysfunction (time frame: On day 367 post investigational medicinal product application). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05365672, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Apr 2025.