Living donor kidney transplantation MedDRA version: 20.0 Level: LLT Classification code 10023438 Term: Kidney transplant System Organ Class: 10042613 - Surgical and medical procedures
Conditions
Interventions
Product Name: MIC
Pharmaceutical Form: Suspension for injection
Other descriptive name: Allogeneic peripheral blood mononuclear cells incubated in vitro with mitomycin C
Concentration unit: million or
Sponsors
TolerogenixX GmbH
Eligibility
Sex/Gender
All
Inclusion 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 [GFR] =65 years) yes F.1.3.1 Number of subjects for this age range 40
Exclusion criteria
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 10. Active bacterial, mycotic or viral infection 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 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 6. Negative serological test result f
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Primary: Determine efficacy of MIC treatment in terms of achieving an operational tolerance-like phenotype compared to the SoC therapy;Secondary Objective: Key-secondary: Determine safety of MIC treatment versus SoC therapy based on number of patient-relevant infections as well as efficacy in terms of biopsy proven acute rejection, graft loss, graft dysfunction, or death Secondary: Determine safety and efficacy of MIC treatment based on further parameters Other: Determine safety and efficacy of MIC treatment based on other parameters;Primary end point(s): Proportion of patients who achieve an operational tolerance-like phenotype defined on Visit Day 367 as fulfilling all of the following criteria: • No acute rejection (biopsy-proven as >Banff Borderline or clinically suspected rejection according to evaluation of adjudication committee), graft loss, graft dysfunction (eGFR 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 Breg =3% measured on Visit Day 367 (patient has to be infection-free at time-point of measurement) • 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 ;Timepoint(s) of evaluation of this end point: • On day 367 • On day 0, 6, 37, 97,142, 187, 277, 367 • On day 367 • At day 277 and day 367 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Key secondary: • Number of patient-relevant infections during the first year after transplantation • 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 Secondary: • AEs including serious AEs and AEs of special interest • Frequency of local or systemic reactions as result of MIC application • Patient-, graft and death-censored graft survival • Incidence of biopsy-proven acute rejections and time to first rejection (>Banff Borderline) according to Banff 2018 criteria and confirmed by a blinded central pathologist • Molecular scores in molecular microscope diagnostic system (MMDx) reading on Visit Day 367 • 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 • 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 • 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 • eGFR (according to chronic kidney disease epidemiology collaboration [CKD-EPI]) • Incidence of CMV reactivation (CMV-DNA =1,000 copies/mL) • Incidence of BK virus replication =1,000 copies/mL • Incidence of BK virus associated nephropathy • Incidence of hospital readmissions after transplant surgery • Days in hospital, on intensive care (ICU)/intermediate care (IMC) and hours on mechanical ventilation upon re-admission • Change of quality of life (SF-36) on Visit Day 367 compared to Baseline • Incidence of new-onset diabetes mellitus after transplantation (fasting plasma glucose =7.0 mmol/L / 126 mg/dL with no calorie intake for at le | — |
Countries
Germany
Contacts
Public ContactCEO
TolerogenixX GmbH
Outcome results
None listed