Reference Group Trial for The ONE Study

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

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.

Study Overview

• Status: Completed
• Conditions: End-stage Renal Failure; Kidney Graft Rejection
• Intervention / Treatment: Other: Blood drawing for immune monitoring and questionnaires

• Study Type: Interventional
• Enrollment (Actual): 70
• Phase: Phase 4

Contacts and Locations

Study Locations

• France
  • Nantes, France, 44093
    • CHU de Nantes Hôtel-Dieu
• Germany
  • Berlin, Germany, 13353
    • Charité Campus Virchow-Klinikum
  • Regensburg, Germany, 93053
    • University Hospital Regensburg
• Italy
  • Milan, Italy, 20132
    • Ospedale San Raffaele
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guy's Hospital in affiliation with King's College London
  • Oxford, United Kingdom, OX3 7LE
    • Churchill Hospital in affiliation with the University of Oxford
• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

Organ Donor:

A prospective donor is eligible for the research if all of the following inclusion criteria apply:

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 Subprojects
5. Willing to provide personal and medical/biological data for the trial
6. 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:

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 subprojects
5. 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:

1. Genetically identical to the prospective organ recipient at the HLA loci
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).

Organ Recipient:

1. Patient has previously received, or is scheduled to receive, any tissue or organ transplant other than the planned kidney graft
2. Known sensitivity to tacrolimus, mycophenolate, or corticosteroids
3. Genetically identical to the prospective organ donor at the HLA loci
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. HIV-positive, EBV-negative or suffering chronic viral hepatitis
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 local 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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Reference Group; 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Time Frame
incidence of patients treated for subclinical acute rejection	60 weeks
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

Other Outcome Measures

Outcome Measure	Time Frame
Immune Monitoring (IM) assessment	60 weeks
Health Economics (HEC) assessment	60 weeks

Collaborators and Investigators

• Sponsor: University of Regensburg
• Collaborators: European Commission
• Investigators: Study Director: Edward K. Geissler, Ph.D., University of Regensburg

Publications and helpful links

General Publications

• 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, Boger CA, Scotta 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, Ollinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyo 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. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7. Erratum In: Lancet. 2020 Jun 27;395(10242):1972.

Helpful Links

• The ONE Study

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: July 31, 2012
• First Submitted That Met QC Criteria: August 1, 2012
• First Posted (Estimate): August 2, 2012

Study Record Updates

• Last Update Posted (Estimate): March 9, 2016
• Last Update Submitted That Met QC Criteria: March 8, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: kidney transplantation; acute rejection; renal transplantation; graft rejection; gold standard treatment; immune monitoring; living-donor
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency; Renal Insufficiency, Chronic; Kidney Failure, Chronic
• Other Study ID Numbers: ONErgt11; 260687 (Other Grant/Funding Number: EU FP7 Programme); 2011-004301-24 (EudraCT Number)