A clinical trial applying Regulatory T cells in liver transplant recipients to investigate the safety and tolerability when stopping standard immunosuppression.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Charite Universitaetsmedizin Berlin KöR

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02]

Trial duration

21 Jul 2025 → ongoing

Decision date (initial)

2025-02-06

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

Determine that autologous polyclonal ex-vivo expanded Tregs (Treg02) therapy in liver transplant recipients who are already receiving tacrolimus monotherapy is safe, well tolerated and modulates the immunologic response in the patient to enable permanent withdrawal of immunosuppression

Secondary objectives 2

1. investigating preliminary efficacy of Treg02 on graft survival and function
2. investigate the effect of Treg02 on quality-of-life and immune cell subsets in peripheral blood

Conditions and MedDRA coding

Solid organ transplantation (Liver)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Adult patients (≥18 years of age) with end-stage liver disease who have had single liver transplant
2. >24 months, < 60 months from the date of liver transplantation
3. Stable liver function as determined by clinical studies; direct bilirubin (< 17.1 µmol/l or 1 mg/dl, total bilirubin < 2.2 mg/dl, albumin > 3 g/l and ALT < 62 IU/l (< 2 ULN).
4. Inflammation grade < 4 and fibrosis stage < 3 in accordance with grading and staging recommendations
5. RAI < 3 at the last biopsy or at inclusion
6. At least 6 months stable on tacrolimus monotherapy with target trough levels of 5 ng/ml without complications
7. No evidence of hepatic autoimmune disease (primary biliary cholangitis, primary sclerosing cholangitis, autoimmune hepatitis)
8. Haematology: Hb ≥ 7.0 g/dl; platelets ≥ 80x10^9/l; total leukocyte count: ≥ 3.0x10^9/l
9. In the investigator’s opinion, is able and willing to comply with all the trial requirements
10. Willing and able to give signed and dated informed consent* for participation in the trial participate in the trial
11. Negative SARS-CoV-2 test (depending on current recommendations)
12. No evidence of marked abnormality in latest liver protocol biopsy around 1 year post LT or at inclusion

Exclusion criteria 14

1. Patient has previously received any tissue or organ transplant other than single liver transplant
2. Known contraindication to the protocol-specified treatments / medications
3. Liver transplant dysfunction defined as fibrosis stage >3, Albumin <3 g/l and ALT >62 IU/l (>2 ULN)
4. Severe irreversible obstructive or restrictive lung disease
5. Previous treatment with any desensitization procedure with or without intravenous immunoglobulin
6. HCC patients with high risk of recurrence as defined >G1/2, >L0, >V0 and > unifocal as defined by Edmondson-Steiner HCC grading scheme
7. Concomitant malignancy or history of malignancy prior to study inclusion in the trial (excluding successfully treated non-metastatic basal/squamous cell carcinoma of the skin, successfully embolized HCC)
8. Active or systemic immune disease that precludes discontinuation of immunosuppression
9. Evidence of significant local or systemic infection
10. HCV-RNA serum positive, HIV positive, HBV surface antigen or HBV-DNA detected in serum at the day of inclusion into the trial
11. Ongoing treatment with systemic immunosuppressive drugs other than tacrolimus at study entry
12. Malignant or pre-malignant haematological conditions. Multiple myeloma, light or heavy chain deposition disease
13. Participation in another clinical trial during the study or within 5 times as the half-life time of the drug used in the previous trial prior to planned study entry
14. Known allergy/hypersensitivity to any component of the study product

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

1. Primary safety endpoint 1: Acute toxicity associated with infusion of Treg02 will be assessed by evidence of: (a) pulmonary complications, (b) immunological reactions resulting in anaphylactic reactions, immediate cardiovascular compromise, or other acute organ failure, (c) Treg therapy associated biochemical perturbation (significant deviations in biomarker data) as assessed by the immunological impact of the infused cells or apoptosis of Tregs and release of cellular contents
2. Primary safety endpoint 2: Over-suppression of the immune system by assessing evidence of: (a) major and/or opportunistic infections, especially increased frequency of CMV, EBV and HBV, HCV reactivation and/or disease, (b) (early) development of neoplasia, (c) relevant anomalies in laboratory analysis unrelated to the transplanted liver functions
3. Primary clinical endpoint: Incidence of acute and/or chronic rejection and the prevalence of AEs. The principal measure of immunomodulation is biopsy-proven acute rejection (BPAR) within 14 months following Treg transfer. Histopathological grading of biopsy material will be assessed by the established Banff criteria.

Secondary endpoints 6

1. Secondary indices of efficacy 1: Prevention of acute rejection: (a) Time to acute rejection episode, (b) Severity of acute rejection episodes based on response to treatment and histological scoring, (c) The level of total immunosuppression at the final trial visit
2. Secondary indices of efficacy 2: Incidence of patients treated for subclinical acute rejection based on histopathological findings
3. Secondary indices of efficacy 3: Prevention of chronic graft dysfunction (chronic rejection) will be assessed by clinically impaired levels of liver enzymes) and histopathological (Banff staging) criteria measures
4. Secondary indices of efficacy 4: Reduced incidence of adverse events/rejections following tapering of immunosuppression (e.g. cardiovascular complications, drug toxicity, etc.)
5. Biomarker panel: Measure functional and molecular indices reflecting the immune response as well as treatment safety and efficacy of Tregs by a validated set of biomarkers; as detailed in the Clinical trial protocol.
6. Assess health-related quality of life by the SF-12 questionnaire

Investigational products

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

Test 4

Auxiliary 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Charite Universitaetsmedizin Berlin KöR

Sponsor organisation

Charite Universitaetsmedizin Berlin KöR

Address

Augustenburger Platz 1, Wedding Wedding

City

Berlin

Postcode

13353

Country

Germany

Scientific contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Prof. Dr. med. Petra Reinke

Public contact point

Organisation

Charite Universitaetsmedizin Berlin KöR

Contact name

Prof. Dr. med. Petra Reinke

Third parties 2

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

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 12 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

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