Eight-Treg study: a phase I dose escalation trial of adoptive immunotherapy with autologous ex vivo expanded regulatory CD8+ T cells in living donor kidney transplant recipients

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire De Nantes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Not possible to specify

Trial duration

3 Mar 2025 → ongoing

Decision date (initial)

2024-12-20

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: Safety

To evaluate the safety of an IV infusion of the experimental drug “Eight Treg” the day before the graft in combination with classical maintenance IS drugs (corticosteroids, tacrolimus, MPA) in renal transplant recipients from a living donor up to 3 months post-transplantation.

Secondary objectives 3

1. To evaluate the long-term safety of the infusion of the experimental drug “Eight Treg” on the (absence or low) occurrence of a dose limiting toxicity at 6 and 12 months post-graft and (no or low stage of) graft inflammation at 3-months post-graft
2. To evaluate exploratory efficacy criteria of the experimental drug “Eight Treg” translationally on the (lower) total immunosuppressive burden at one post-transplant year and on the (lower) incidence, duration and severity of infections during the first year post-graft compared to historical data from previously reported studies using standard IS regimens
3. To deepen fundamental knowledges on CD8+ Tregs such as their persistence and migration to the graft after infusion and their impact on graft inflammation, peripheral blood immune cells counts, phenotype and reactivity against donor cells, from before to 12 months post transplant and compared CD8+Tregs in patients with standard IS regimens

Conditions and MedDRA coding

chronic renal failure requiring kidney transplantation

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Man or woman with chronic renal failure requiring kidney transplantation and approved to receive a primary kidney allograft from a living donor.
2. Speaking and understanding French
3. Weight between 50 and 100 kg
4. Up-to-date vaccination against SARS Cov2 depending on the health situation and the rules in force with last recall done at least 6 to 1 month prior to visit 1
5. Negative microlymphocytotoxicity (LCT) and flow cytometry crossmatches regardless of HLA compatibility
6. Signed and dated written informed consent
7. Aged at least of 18 years the day the consent is signed
8. Able to commence the IS regimen at the protocol-specified time point
9. As a precautionary measure, women of childbearing age should use an effective method of birth control, and male participants should use contraception to avoid partner pregnancy for the duration of the trial.
10. Affiliated or beneficiary of a social security scheme

Exclusion criteria 19

1. Patient has previously received any tissue or organ transplant other than the planned kidney graft
2. Any vaccine (or vaccine recall) dated within 3 months on visit 1 except the SARS Cov2
3. Participation in another clinical trial during the study or within 28 days prior to the planned study entry and / or exposure to an investigational product during the study or within 28 days prior to the planned study entry (date of signature of the consent collection form).
4. Women who are pregnant (or planning to be during the course of the study) or breastfeeding or women with a positive pregnancy test on enrolment (visit 1, screening failure).
5. Psychological, familial, sociological or geographical factors that potentially hampering compliance with the study protocol and follow-up visit schedule
6. Any form of drug abuse, psychiatric disorder, or other condition that, in the opinion of the investigator, may invalidate communication with the investigator and/or designated study personnel
7. Any pro-coagulant disposition, as evidences by a past history of thromboembolic disease or abnormal laboratory coagulation parameters which, in the judgement of the investigator, would place the subject at undue risk
8. Any condition resulting in a substantial reduction in the volume of the pulmonary vasculature or an increase in the pulmonary vascular resistance. Any disease or disease process leading to substantially elevated pulmonary arterial pressure (as evidences by electrocardiography, echocardiography, radiology or cardiac catheterization) or right heart hypertrophy or dysfunction.
9. Known atrial or ventricular septal defects posing a risk of paradoxical embolism of infused cells or cell aggregates.
10. Patients unable to freely give their informed consent (e.g. patients under guardianship, curatorship, protection of justice).
11. Patients deprived of their liberty.
12. Genetically identical to the prospective organ donor at the HLA loci
13. Known contraindication to the protocol-specified treatments / medications or components used in the manufacture of the experimental drug
14. Previous treatment with any desensitisation procedure (with or without IVIg)
15. Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal / squamous cell carcinoma of the skin).
16. Evidence of significant local or systemic infection on visit 1
17. Malignant or pre-malignant haematological conditions
18. Ongoing treatment with systemic IS drugs at visit 1 (except corticoids < 10 mg).
19. 4. Panel Reactive Antibodies (PRA) or “Taux de Greffons Incompatibles” (TGI) grade > 0 within 6 months prior to enrolment.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Occurrence of a dose-limiting toxicity up to visit 10, at 3 months post-graft. A Dose-Limiting Toxicity (DLT) is defined as a clinically significant AE or abnormal laboratory value:  Unrelated to the kidney transplant, intercurrent illness, or concomitant medications  Grade 3, 4 or 5 non-hematologic toxicity (with exceptions)

Secondary endpoints 4

1. Occurrence of a DLT up to 6- and 12-months post-graft, and anatomopathological and im-munohistological (HD) analysis of the graft biopsies at 1- and 3-months post-graft.
2. Incidence, duration and severity of infections, and total immunosuppressive burden at one-year post-graft.
3. 3 Real time follow-up of blood cell count, analysis of the DSA and of cytokines in plasma and urine; kinetic of absolute count of blood cells and high density spectral immunophenotyping at protein and transcriptional levels of PBMC; tracking the infused cells in blood; identifying Tregs clones emerging; evaluating the suppressive capacity of circulating Tregs; evaluating the reac-tivity of circulating T cells ; immunohistochemical staining and spatial transcriptomic of graft biopsies
4. 4 Comparison of blood Tregs profile, emerging clones, and donor reactive T cells; and perturba-tion of graft infiltrate after cell therapy compared to standard treatment from a control biocollec-tion (DIVAT declared on 09/05/2011 under the n°DC-2011-1399) and historical databases.

Investigational products

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

Test 1

Auxiliary 6

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire De Nantes

Sponsor organisation

Centre Hospitalier Universitaire De Nantes

Address

5 Allee De L Ile Gloriette, Cs 69301 Cs 69301

City

Nantes Cedex 1

Postcode

44093

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Diego CANTAROVICH

Public contact point

Organisation

Centre Hospitalier Universitaire De Nantes

Contact name

Diego CANTAROVICH

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

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