Reference Group Trial for The ONE Study

Study Description

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Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
End-stage Renal Failure; Kidney Graft Rejection	Other: Blood drawing for immune monitoring and questionnaires	Phase 4

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	70 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Basic Science
Official Title:	Reference Group Trial for The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation
Study Start Date :	December 2012
Actual Primary Completion Date :	December 2015
Actual Study Completion Date :	December 2015

Arms and Interventions

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Arm

Intervention/treatment

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

Outcome Measures

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Primary Outcome Measures :

1. biopsy-confirmed acute rejection incidence [ Time Frame: 60 weeks ]

Secondary Outcome Measures :

1. time to first acute rejection episode [ Time Frame: within 60 weeks ]
2. severity of acute rejection episodes [ Time Frame: within 60 weeks ]
3. total immunosuppressive burden [ Time Frame: 60 weeks ]
4. incidence of chronic graft dysfunction [ Time Frame: 60 weeks ]
5. incidence of graft loss through rejection [ Time Frame: 60 weeks ]
6. incidence of adverse drug reactions [ Time Frame: 60 weeks ]
7. incidence of major infections [ Time Frame: 60 weeks ]
8. incidence of neoplasia [ Time Frame: 60 weeks ]
9. incidence of patients treated for subclinical acute rejection [ Time Frame: 60 weeks ]

Other Outcome Measures:

1. Immune Monitoring (IM) assessment [ Time Frame: 60 weeks ]
2. Health Economics (HEC) assessment [ Time Frame: 60 weeks ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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).

Contacts and Locations

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Locations

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

Sponsors and Collaborators

University of Regensburg

European Commission

Investigators

Study Director:	Edward K. Geissler, Ph.D.	University of Regensburg

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

The ONE Study 

Responsible Party:	Edward Geissler, Chief Investigator and EU Project Leader, University of Regensburg
ClinicalTrials.gov Identifier:	NCT01656135 History of Changes
Other Study ID Numbers:	ONErgt11; 260687 ( Other Grant/Funding Number: EU FP7 Programme ); 2011-004301-24 ( EudraCT Number )
First Posted:	August 2, 2012
Last Update Posted:	March 9, 2016
Last Verified:	March 2016

Keywords provided by Edward Geissler, University of Regensburg:

gold standard treatment; immune monitoring; acute rejection; graft rejection	living-donor; renal transplantation; kidney transplantation

Additional relevant MeSH terms:

Renal Insufficiency; Kidney Failure, Chronic; Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic