Reference Group Trial for The ONE Study

Study Overview
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Brief Summary
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To investigate the progression of the immunological response in living-donor kidney transplant recipients treated with a standard immunosuppressive regimen. Clinical, immunological, and health-economic data collected during this Reference Group Trial will be used to corroborate historical renal transplantation statistics and generate reference ranges for future clinical studies that will test immunoregulatory cell therapy as an adjunct immunosuppressive treatment in renal transplantation.

Official Title
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Reference Group Trial for The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation

Conditions
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End-stage Renal Failure, Kidney Graft Rejection

Intervention / Treatment
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* Other: Blood drawing for immune monitoring and questionnaires


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Organ Donor: A prospective donor is eligible for the research if all of the following inclusion criteria apply: Eligible for live kidney donation Aged at least 18 years An ABO blood type compatible with the organ recipient Willing and able to provide a blood sample for The ONE Study Subprojects Willing to provide personal and medical/biological data for the trial Signed and dated written informed consent. In signing the donor information sheet/informed consent form (DIS/ICF), organ donors agree to provide a blood sample for the IM Subproject, and permit access to their medical records for the collection of specified demographic and medical/biological data for the trial. Organ Recipient: Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor Aged at least 18 years Able to commence the immunosuppressive regimen at the protocol-specified time point Willing and able to participate in The ONE Study subprojects Signed and dated written informed consent. Exclusion Criteria: Organ Donor: If a prospective donor fulfils any of the following criteria, then they are ineligible for the trial: Genetically identical to the prospective organ recipient at the HLA loci Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation 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 Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship). Organ Recipient: Patient has previously received, or is scheduled to receive, any tissue or organ transplant other than the planned kidney graft Known sensitivity to tacrolimus, mycophenolate, or corticosteroids Genetically identical to the prospective organ donor at the HLA loci PRA grade > 40% within 6 months prior to enrolment Previous treatment with any desensitisation procedure (with or without IVIg) 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) Evidence of significant local or systemic infection HIV-positive, EBV-negative or suffering chronic viral hepatitis Significant liver disease, defined as persistently elevated AST and/or ALT levels >2 x ULN (Upper Limit of Normal range) Malignant or pre-malignant haematological conditions Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives Any condition which, in the judgement of the Investigator, would place the subject at undue risk Ongoing treatment with systemic immunosuppressive drugs at study entry Participation in another clinical trial during the study or within 28 days prior to planned study entry Female patients of child-bearing potential with a positive pregnancy test at enrolment Female patients who are breast-feeding All female patients of child-bearing potential UNLESS: The patient is willing to maintain a highly effective method of birth control for the duration of the study 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 local Investigator) Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule 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 Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Reference Group<br>Basiliximab (Simulect®): Day 0: 20mg IV ≤2h prior to surgery Day 4: 20mg IV Prednisolone: Day 0: 500mg IV (250mg pre-op, 250mg intra-op) Day 1: 125mg IV Day 2 - 14: 20mg/day oral Week 3 - 4: 15mg/day oral Week 5 - 8: 10mg/day oral Week 9 - 12: 5mg/day oral Week 13 - 14: 2.5mg/day oral Week 15 - Study End: Cessation Steroid tapering should not proceed if graft rejection has occurred or if renal dysfunction is observed. Mycophenolate Mofetil (MMF, or biologic equivalent): Treatment with MMF should commence one day prior to transplantation (on Day -1) and should continue indefinitely, with a dose reduction after two weeks: Day -1 - 14: 2g/day oral Day 15 - Study End 1.5g/day oral (750mg twice daily) Tacrolimus (or biologic equivalent): Day -4 - 14: 3-12ng/ml Week 3 - 12: 3-10ng/ml Week 13 - 36: 3-8ng/ml Week 37 - Study End: 3-6ng/ml | Other: Blood drawing for immune monitoring and questionnaires<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| biopsy-confirmed acute rejection incidence |  | 60 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to first acute rejection episode |  | within 60 weeks | 
| severity of acute rejection episodes |  | within 60 weeks | 
| total immunosuppressive burden |  | 60 weeks | 
| incidence of chronic graft dysfunction |  | 60 weeks | 
| incidence of graft loss through rejection |  | 60 weeks | 
| incidence of adverse drug reactions |  | 60 weeks | 
| incidence of major infections |  | 60 weeks | 
| incidence of neoplasia |  | 60 weeks | 
| incidence of patients treated for subclinical acute rejection |  | 60 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gold standard treatment, immune monitoring, acute rejection, graft rejection, living-donor, renal transplantation, kidney transplantation