A non blinded phase-II study with 3 randomized patient groups of individualized suppression of the patient's immune system with donor modified immune cells (MIC) compared to standard-of-care in kidney transplantation from living donors

Phase 1

• Conditions: iving donor kidney transplantation; MedDRA version: 20.0Level: LLTClassification code 10023438Term: Kidney transplantSystem Organ Class: 10042613 - Surgical and medical procedures; Therapeutic area: Body processes [G] - Immune system processes [G12]

• Registration Number: EUCTR2021-000561-33-DE
• Lead Sponsor: TolerogenixX GmbH

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-07-08
• Last Update Posted: 29 July 2024

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 126

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] <15 mL/min and/or on renal replacement therapy), who are in preparation for kidney transplantation from a live donor
2. Age =18 years, <75 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 (SARS-CoV-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:
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.
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.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 86
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

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 e 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

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified