A clinical trial applying Regulatory T cells in kidney transplant recipients to investigate the safety and tolerability as an adjunctive therapy to the standard immunosuppressive therapy

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

10 Jun 2024 → ongoing

Decision date (initial)

2024-11-01

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-514398-23-00

EudraCT number

2021-006558-29

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Determine whether administering polyclonal ex-vivo expanded autologous Tregs to deceased donor kidney transplant recipients is safe. Investigate if adoptive Treg therapy modulates the immunological response such that the kidney transplant is tolerated and safe. Yield preliminary data that Treg therapy could potentially enable maintenance immunosuppressive therapy tapering or elimination, thereby improving recipients’ long-term prognosis.

Conditions and MedDRA coding

Solid organ transplantation (Kidney)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Chronic renal insufficiency with a GFR < 15 ml/min x 1.73 m², accepted by the organ transplantation conference, registered by ET (Eurotransplant; www.eurotransplant.org)
2. Age: 18 – 70 years of age
3. Willing and able to participate in the trial
4. Signed and dated written informed consent.* (*For patients unable to read and/or write, an oral informed consent observed by an independent witness is acceptable, if the patient has fully understood the oral information given by the Investigator. The witness should sign the consent form on behalf of the patient.)
5. Haematology: Hb ≥7.0 g/dl; platelets ≥80x10^9/l; total leukocyte count: ≥3.0x10^9/l
6. Karnofsky score: 40 – 90
7. Donor eligibility criteria: Individuals 18 years of age or more are eligible as donors. However, potential donors >50 years will be not eligible if they have more than 2 of the following risk factors; hypertension or serum creatinine >1.5 mg/dl at the time of explantation or an anticipated cold ischemia time of >24 h.

Exclusion criteria 29

1. Patient has previously received any tissue or organ transplant other than the planned kidney graft
2. HIV-positive or suffering chronic viral hepatitis
3. Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN (Upper Limit of Normal range)
4. Malignant or pre-malignant haematological conditions. Multiple myeloma, light or heavy chain deposition disease
5. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
6. Any condition which, according to the PI, would place the subject at undue risk
7. Ongoing treatment with systemic immunosuppressive drugs at study entry
8. 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
9. Female patients of childbearing age with a positive pregnancy test at enrolment
10. Female patients who are breast-feeding
11. All female patients of childbearing age* unless the patient is willing to maintain a highly effective method of birth control** for the duration of the study
12. Known contraindication to protocol-specified treatments / medications
13. AL amyloidosis with significant extrarenal involvement
14. Decompensated cirrhosis
15. Severe irreversible obstructive or restrictive lung disease
16. Severe uncorrectable and symptomatic cardiac disease that is deemed by cardiologists to preclude transplantation
17. Progressive central neurodegenerative disease
18. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
19. Any form of drug or alcohol abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel
20. Patients unable to give their informed consent (e.g. patients under legal guardianship)
21. Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
22. Known allergy/hypersensitivity to any component of the study product
23. Positive SARS-CoV-2 RT-PCR test
24. Persons who demonstrate dependency from the sponsor, investigator or trial site
25. Panel-reactive antibodies (PRA) grade > 20% within last 6 months before enrolment
26. Previous treatment with any desensitization procedure with or without intravenous immunoglobulin
27. Concomitant malignancy or history of malignancy within 5 years prior to study inclusion in the trial (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin or curatively treated renal cell carcinoma with complete nephrectomy)
28. Evidence of significant local or systemic infection
29. EBV-negative recipient receiving a kidney from an EBV-positive deceased-donor

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 4

1. Primary safety endpoint 1: Acute toxicity associated with infusion of Treg02, 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 cytomegalovirus (CMV), Epstein-Barr virus (EBV) and polyomavirus reactivation and/or disease, (b) early development of neoplasia
3. Primary safety endpoint 3: Chronic toxicity associated with Treg02 infusions, measured by evidence of: (a) malignancies arising directly from adoptive cellular therapy, (b) autoimmune disorders, (c) inflammatory pathologies, (d) anaemia, cytopenia or biochemical anomalies unrelated to the transplanted kidney functions
4. Primary clinical endpoint: Biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation

Secondary endpoints 7

1. Secondary indices of efficacy 1: Prevention of acute rejection (a): time to first acute rejection, b): severity of acute rejection episodes based on response to treatment and histological scoring, c): 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 or interstitial fibrosis/tubular atrophy) assessed by clinically impaired glomerular filtration rate (GFR) and histopathological (Banff staging) criteria measures
4. Secondary indices of efficacy 4: Incidence of post-transplant dialysis, inclusion on the transplant waiting list, or re-transplantation following graft loss through rejection (acute or chronic)
5. Secondary indices of efficacy 5: Reduced incidence of adverse events/rejections following tapering of immunosuppression (e.g. cardiovascular complications, drug toxicity, etc.)
6. Biomarker panel: measure functional and molecular indices reflecting the immune response as well as treatment safety and efficacy of regulatory T cells
7. Quality-of-life using the SF-12 QoL health survey

Investigational products

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

Test 7

Auxiliary 6

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 17 files

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

Application history

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