The ONE Study ATDC Trial

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-03-19

Study Completion Date

2018-11-14

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

To collect evidence of the safety of administering autologous tolerogenic dendritic cells (ATDC) preparations to living-donor renal transplant recipients in the context of an international European Union funded consortium aimed at evaluationg cellular immunotherapy in solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced by ATDC therapy can evntually be used to reduce the need for conventional immunosuppression in transplant recipients.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Donor-Alloantigen-Reactive Regulatory T Cell (darTreg) Therapy in Renal Transplantation (The ONE Study )

NCT02244801

Kidney Disease

COMPLETED PHASE1

The ONE Study UK Treg Trial

NCT02129881

End-stage Renal Failure

COMPLETED PHASE1/PHASE2

Reference Group Trial for The ONE Study

NCT01656135

End-stage Renal Failure Kidney Graft Rejection

COMPLETED PHASE4

The ONE Study nTreg Trial (ONEnTreg13)

NCT02371434

Immunosuppressive Treatment of Living-donor Renal Transplantation

COMPLETED PHASE1/PHASE2

Assessment of T-cell Response and In-vitro Proof-of-concept of T-cell Engineering in Chronic ESKD Patients.

NCT06474169

Chronic Kidney Diseases

RECRUITING

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Decades of immunosuppressive drug development have produced an array of powerful pharmacological agents, but the various drawbacks associated 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 ONE Study aims to answer the question as whether ATDC treatment, or immunoregulatory cell-based therapy in general, has any place in the clinical management of solid organ transplant recipients.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Renal Failure, End Stage

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

ATDC Treatment

ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation.

Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus, as detailed below :

Prednidolone :

* D 0: 500 mg IV
* D 1: 125 mg IV
* D 2 to 14: 20.0 mg/d
* Wk 3 to 4: 15.0 mg/d
* Wk 5 to 8: 10.0 mg/d
* Wk 9 to 12: 5.0 mg/d
* Wk 13 to 14: 2.5 mg/d
* Wk 15 to End:Cessation

MMF (or biologic equiv.):

* D -7 to -2: 500 mg/d (250mg 2x/d)
* D -1 to 14: 2000 mg/d
* Wk 3 to 36: 1000 mg/d
* Wk 37 to 40: 750 mg/d
* Wk 41 to 44: 500 mg/d
* Wk 45 to 48: 250 mg/d
* Wk 49 to End:Cessation Note : MMF tapering will only happen if the 36-week protocol biopsy shows no signs of subclinical rejection and there is evidence of declining renal function or if the clinician has any other concern about MMF dose reduction.

Tacrolimus :

* ≤ 48 h pre-Tx to D 14: 3-12 ng/ml
* Wk 3 to 12: 3-10 ng/ml
* Wk 13 to 36: 3-8 ng/ml
* Wk 37 to End: 3-6 ng/ml

Group Type EXPERIMENTAL

ATDC_Nantes

Intervention Type BIOLOGICAL

ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation into recipients also recipients of a living donor renal transplantation.

Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus background immunosuppression ( as described in detail in the arm description)

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

ATDC_Nantes

ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation into recipients also recipients of a living donor renal transplantation.

Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus background immunosuppression ( as described in detail in the arm description)

Intervention Type BIOLOGICAL

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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. Eligible for leucapheresis prior to organ transplantation
6. Signed and dated written informed consent

1. Eligible for live kidney donation
2. Willing and able to provide a blood sample for The ONE Study IM Subproject
3. Willing to provide personal and medical/biological data for the trial analysis
4. Signed and dated written informed consent

Exclusion Criteria

1. Patient has previously received any tissue or organ transplant other than the planned kidney graft
2. Known contraindication to the protocol-specified treatments / medications (like known allergies to heparin)
3. Genetically identical to the prospective organ donor at the HLA loci (A.B.DR 0 mismatch)
4. PRA grade \> 0 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. ABO incompatibility
8. Presence of DSA (donor specific antibodies) detected by luminex prior transplantation
9. Evidence of significant local or systemic infection
10. HIV-positive, EBV-negative or suffering chronic viral hepatitis, syphilis serology- positive
11. Significant liver disease, defined as persistently elevated AST and/or ALT levels \> 2 x ULN (Upper Limit of Normal range)
12. Malignant or pre-malignant haematological conditions
13. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
14. Any condition which, in the judgement of the Investigator, would place the subject at undue risk
15. Ongoing treatment with systemic immunosuppressive drugs at inclusion (despite corticoids lower than 10 mg)
16. Participation in another clinical trial during the study or within 28 days prior to planned study entry
17. Exposure to an investigational product during the study or within 28 days prior to planned study entry
18. Female patients of child-bearing potential with a positive pregnancy test at enrolment and F01
19. Female patients who are breast-feeding
20. 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)
21. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
22. 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
23. Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

Criteria specific to the infusion of the ATDC\_Nantes:
24. Any pro-coagulant disposition, as evidenced 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
25. 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 evidenced by electrocardiography, echocardiography, radiology or cardiac catheterisation) or right heart hypertrophy or dysfunction
26. Known atrial or ventricular septal defects posing a risk of paradoxical embolism of infused cells or cell aggregates
27. Known hypersensitivity to any component of the cell product or components used in the manufacture of the cell product.

DONOR

1. Genetically identical to the prospective organ recipient at the HLA loci (A.B.DR 0 mismatch)
2. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation
3. 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
4. Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship).
5. ABO incompatibility

Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No