A prospective controlled trial to evaluate safety and efficacy of in vitro expanded recipient regulatory T cell therapy and tocilizumab together with donor bone marrow infusion in HLA-mismatched living donor kidney transplant recipients (Trex)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

Trial duration

24 Apr 2019 → ongoing

Decision date (initial)

2024-05-31

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-513459-34-00

EudraCT number

2018-003142-16

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

1) To examine the safety of Treg therapy together with tocilizumab and donor bone marrow in living donor kidney transplant recipients.
2) To assess chimerism levels within the first month post-transplant.

Secondary objectives 6

1. To demonstrate that the study protocol allows the initiation of a step-wise reduction of immunosuppression up to a point when patients receive drug monotherapy.
2. To gain insight as to whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.
3. To assess the frequency of biopsy-proven acute rejection episodes.
4. To assess the frequency of subclinical rejection episodes on surveillance biopsies.
5. To assess kidney graft function.
6. To assess the area-under-the-curve (AUC) of chimerism.

Conditions and MedDRA coding

Kidney transplantation

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 14

1. For recipients (study and control group): Patient has provided written informed consent.
2. For recipients (study and control group): Patient is 18 years or older.
3. For recipients (study and control group): Patient is a planned recipient of a living donor kidney transplant.
4. For recipients (study and control group): Patient is a planned recipient of an ABO-compatible kidney graft.
5. For recipients (study and control group): Patient is a planned recipient of a kidney graft from a donor that is not HLA-identical.
6. For recipients (study and control group): Patient is negative for DSA.
7. For recipients (study and control group): WOCBP must have a negative pregnancy test at inclusion.
8. For recipients (study and control group): WOCBP must be using an adequate method of contraception to avoid pregnancy throughout the study and for up to 12 weeks after the study in such a manner that the risk of pregnancy is minimized.
9. For donors (study group only): Participant has provided written informed consent.
10. For donors (study group only): Participant is 18 years or older.
11. For donors (study group only): Participant is suitable to donate bone marrow according to the guidelines of the Department of Blood Group Serology and Transfusion Medicine.
12. For donors (study group only): WOCBP must not be pregnant at inclusion (i.e. negative pregnancy test).
13. For donors (control group only): Participant has provided written informed consent to donate blood for immune monitoring analyses.
14. For donors (control group only): Participant is 18 years or older.

Exclusion criteria 9

1. For recipients (study and control group): Patient is EBV-negative on serology.
2. For recipients (study and control group): Patient is HIV-positive or suffering from chronic viral hepatitis.
3. For recipients (study and control group): Patient is CMV-negative and receiving a kidney from a CMV-positive donor.
4. For recipients (study and control group): Positive T-cell lymphocytotoxic cross match.
5. For recipients (study and control group): Patient with prior kidney transplant or non-renal solid organ transplant.
6. For recipients (study and control group): Patient has a known contraindication to any of the protocol-specified treatments
7. For recipients (study and control group): Patient had been diagnosed with a malignancy within 5 years prior to study entry, excluding non-metastatic basal or squamous cell carcinoma of the skin.
8. For recipients (study and control group): Female patients who are breast-feeding.
9. For recipients (study and control group): Female patients with a positive pregnancy test.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Co-primary endpoint 1 (safety) is defined as incidence of GVHD, impaired graft function [eGFR <35mL/min/1.73m2] or patient death, whichever occurs first, within 12 months post-transplant.
2. Co-primary endpoint 2 (efficacy) is defined as the individual peak chimerism levels within the first month post-transplant.

Secondary endpoints 6

1. To demonstrate that the study protocol allows the initiation of a step-wise reduction of immunosuppression up to a point when patients receive drug monotherapy.
2. To gain insight as to whether the study protocol leads to detectable changes in the immune system indicative of pro-tolerogenic immune modulation.
3. To assess the frequency of biopsy-proven acute rejection episodes.
4. To assess the frequency of subclinical rejection episodes on surveillance biopsies.
5. To assess kidney graft function.
6. To assess the area-under-the-curve (AUC) of chimerism.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Division of Transplantation

Public contact point

Organisation

Medical University Of Vienna

Contact name

Division of Transplantation

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications