Autologous expanded regulatory CD8+ T cell therapy for living-donor kidney transplant recipients

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

This trial will test whether infusing a patient's own expanded regulatory CD8+ T cells (Eight Treg) around a living-donor kidney transplant can help the graft survive better and lower the need for standard immunosuppressive drugs.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 9 (estimated)
• Ages: 18 Years to 99 Years
• Sex: All
• Sponsor: Nantes University Hospital (Academic / other)
• Locations: 1 site (Nantes)
• Trial ID: NCT06777719 on ClinicalTrials.gov

What this trial studies

This Phase 1, single-center interventional trial at CHU de Nantes administers autologous ex vivo expanded regulatory CD8+ T cells (Eight Treg) to selected adult living-donor kidney recipients alongside the protocol immunosuppressive regimen. Cells are generated from the patient's own immune cells, expanded in the laboratory, and infused to try to promote immune regulation and graft tolerance. The primary aim is to determine safety and feasibility with close monitoring for adverse events and graft function after transplantation. Secondary observations include preliminary signals on immunosuppressive drug requirements and immune biomarkers.

Who should consider this trial

Good fit: Adults (≥18 years) approved for a primary living-donor kidney transplant who weigh 50–100 kg, have negative LCT and flow cytometry crossmatches, speak French, and are affiliated with a social security scheme are the intended candidates.

Not a fit: Patients receiving deceased-donor transplants, those who fail crossmatch screening, minors, non–French speakers, or people with contraindications to cell therapy are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, the therapy could reduce long-term dependence on conventional immunosuppressive drugs and lower related risks such as infections, malignancies, and chronic graft dysfunction.

How similar studies have performed: Early-phase trials of regulatory cell therapies—primarily CD4+ Tregs—have shown acceptable safety and some promising signs of lowering immunosuppression, but CD8+ regulatory T cell therapy is relatively novel with limited human data.

Eligibility criteria

for kidney transplant recipient: pre-Inclusion Criteria:

1. Man or woman with chronic renal failure requiring kidney transplantation and approved to receive a primary kidney allograft from a living donor.
2. Weight between 50 and 100 kg.
3. 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.
4. Negative microlymphocytotoxicity (LCT) and flow cytometry crossmatches regardless of HLA compatibility
5. Signed and dated written informed consent \*.
6. Aged at least of 18 years the day the consent is signed.
7. Able to commence the IS regimen at the protocol-specified time point.
8. 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.
9. Affiliated or beneficiary of a social security scheme.
10. Speaking and understanding French.

Inclusion Criteria:

1. WOCBP must have a negative serum pregnancy test.
2. Respects the following conditions:

   * Condition 1: number of CD8+ Tregs / ml of blood \> 2.096x106 CD8+ Tregs / weight
   * Condition 2 (depending on the dose level considered):

     * Dose 1: number of CD8+ Tregs / ml of blood \> 1.15x104 CD8+ Tregs + 3.18x103 CD8+ Tregs / weight
     * Dose 2: number of CD8+ Tregs / ml of blood \> 4.6x104 CD8+ Tregs + 3.18x103 CD8+ Tregs / weight
     * Dose 3: number of CD8+ Tregs / ml of blood \> 9.22x104 CD8+ Tregs + 3.18x103 CD8+ Tregs / weight

Pre-Exclusion Criteria:

1. Patient has previously received any tissue or organ transplant other than the planned kidney graft.
2. Genetically identical to the prospective organ donor at the HLA loci.
3. Known contraindication to the protocol-specified treatments / medications or components used in the manufacture of the experimental drug.
4. Presence of donor-specific antibodies (DSA) detected prior transplantation determined by Luminex within 3 months or presence of cytotoxic DSA determined by cell-based CDC assay.
5. Previous treatment with any desensitisation procedure (with or without IVIg).
6. 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).
7. ABO incompatibility
8. Evidence of significant local or systemic infection on visit 1.
9. Malignant or pre-malignant haematological conditions.
10. Ongoing treatment with systemic IS drugs at visit 1 (except corticoids \< 10 mg).
11. Any vaccine (or vaccine recall) dated within 3 months on visit 1 except the SARS Cov2\*.
12. 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).
13. 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).
14. Psychological, familial, sociological or geographical factors that potentially hampering compliance with the study protocol and follow-up visit schedule.
15. 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.
16. 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.
17. 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.
18. Known atrial or ventricular septal defects posing a risk of paradoxical embolism of infused cells or cell aggregates.
19. Patients unable to freely give their informed consent (e.g. patients under guardianship, curatorship, protection of justice).
20. Patients deprived of their liberty.

Exclusion Criteria:

1. Human Immunodeficiency Virus (HIV)-positive, Epstein-Barr Virus (EBV)-negative (if donor is EBV positive), HTLV positive, syphilis-positive serology or suffer from chronic viral hepatitis.
2. Significant liver disease, defined as persistently elevated Aspartate Transaminase (AST) and / or Alanine Transaminase (ALT) levels \> 2 x upper limit of normal range.

Donor:

Pre-Inclusion Criteria:

1. Willing and able to provide a blood and an urine sample for the immune monitoring.
2. Willing to provide personal and medical/biological data for the trial analysis.
3. Signed and dated written informed consent \*.
4. Aged at least of 18 years the day the consent is signed.
5. Affiliated or beneficiary of a social security scheme.
6. Speaking and understanding French.

Where this trial is running

Nantes

• CHU de Nantes — Nantes, France (Recruiting)

Study contacts

• Study coordinator: Gilles BLANCHO

Conditions Kidney Transplantation; Kidney transplantation; living donor kidney; immunotherapy; CD8+ T cells