The ONE Study UK Treg Trial

Conditions

End-stage Renal Failure

Brief summary

A study to assess cell therapy as a treatment to prevent kidney transplant rejection. The trial will involve purification of naturally occurring regulatory T cells (nTregs) from living-donor renal transplant recipients. The cells will then be grown in the laboratory and re-infused into the patient five days after the kidney transplant. This trial is part of an international European Union funded consortium aimed at evaluating cellular immunotherapy in solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced by nTreg therapy can eventually be used to recude the need for conventional immunosuppression in transplant recipients.

Detailed description

Decades of immunosuppressive drug development has produced an array of powerful pharmacological agents, but the various drawbacks with these treatments leaves considerable room for improvement. By harnessing the power of suppressive mechanisms in the human immune system, regulatory cell therapy may be able to support peripheral tolerance and induce a level of donor-specific unresponsiveness that allows for a reduction in the use of conventional immunosuppression in organ transplant recipients. Several alternative regulatory cell types have been identified as potential adjunct immunotherapies for solid organ transplantation and are now approaching a stage of development that would allow clinical testing in an early-stage trial. The EU-funded international ONE study consortium aims to answer the question as to whether Treg treatment, or other immunoregulatory cell-based therapies, can be advanced in the clinical management of solid organ transplant recipients. This particular Treg trial aims to explored the potential of Treg therapy as an adjunct immunosuppressive treatment in living-donor renal transplant recipients through a clinical protocol design shared by other investigators in the ONE study group testing additional regulatory cell therapies in seperate trials.

McCallion O, Cross AR, Brook MO, Hennessy C, Ferreira R, Trzupek D, Mulley WR, Kumar S, Soares M, Roberts IS, Friend PJ, Lombardi G, Wood KJ, Harden PN, Hester J, Issa F.

2024-12-277 citations

10.1016/j.medj.2024.11.014

Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials.

Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Böger CA, Scottà C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Öllinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyó J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK.

2020-05-01321 citations

10.1016/s0140-6736(20)30167-7

Interventions

BIOLOGICALAutologous regulatory T Cell Product

Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed in the arm description.

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

No

Inclusion criteria

Recipient Inclusion Criteria 1. Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor 2. Aged at least 18 years 3. Able to commence the immunosuppressive regimen at the protocol-specified time point 4. Willing and able to participate in The ONE Study IM and HEC subprojects 5. Signed and dated written informed consent

Exclusion criteria

1. Patient has previously received any tissue or organ transplant 2. Known contraindication to the protocol-specified treatments / medications 3. Genetically identical to the prospective organ donor at the HLA loci (0-0-0 mismatch) 4. PRA grade \> 40% within 6 months prior to enrolment 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. Evidence of significant local or systemic infection 8. EBV-negative; serologically positive for anti-HIV-1,2; HBsAg; Anti-HBc; Anti-HCV-ab; Anti-HTLV-1,2 or syphilis (Treponema palladium) 9. Significant liver disease, defined as persistently elevated AST and/or ALT levels \> 2 x ULN (Upper Limit of Normal range) 10. Malignant or pre-malignant haematological conditions 11. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives 12. Any condition which, in the judgement of the Investigator, would place the subject at undue risk 13. Ongoing treatment with systemic immunosuppressive drugs at study entry 14. Participation in another clinical trial during the study or within 28 days prior to planned study entry 15. Female patients of child-bearing potential with a positive pregnancy test at enrolment 16. Female patients who are breast-feeding 17. All female patients of child-bearing potential UNLESS: 1. The patient is willing to maintain a highly effective method of birth control for the duration of the study 2. The career, lifestyle, or sexual orientation of the patient ensures that there is no risk of pregnancy for the duration of the study (at the discretion of the Investigator) 18. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule 19. Any form of substance 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 freely give their informed consent (e.g. individuals under legal guardianship). Donor Inclusion Criteria 1. Eligible for live kidney donation 2. Aged at least 18 years 3. An ABO blood type compatible with the organ recipient 4. Willing and able to provide a blood sample for The ONE Study IM Subproject 5. Willing to provide personal and medical/biological data for the trial analysis 6. Signed and dated written informed consent.

Design outcomes

Primary

Measure	Time frame
Incidence of biopsy-confirmed acute rejection.	60 weeks

Secondary

Measure	Time frame
Severity of acute rejection episodes	60 weeks
Total immunosuppressive burden	60 weeks
Incidence of chronic graft dysfunction	60 weeks
Time to first acute rejection episode	60 weeks
Incidence of adverse drug reactions	60 weeks
Incidence of major and/or opportunistic infections	60 weeks
Incidence of neoplasia.	60 weeks
Incidence of graft loss through rejection	60 weeks

Countries

United Kingdom

Outcome results

None listed