Reference Group Trial for The ONE Study

Phase 4

Completed

• Conditions: Kidney Graft Rejection; End-stage Renal Failure
• Interventions: Other: Blood drawing for immune monitoring and questionnaires

• Registration Number: NCT01656135
• Lead Sponsor: University of Regensburg

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2012-07-31
• Study First Submitted QC: 2012-08-01
• Study First Posted: 2012-08-02
• Study Start: 2012-12
• Primary Completion: 2015-12
• Study Completion: 2015-12
• Status Verified: 2016-03
• Last Update Submitted: 2016-03-08
• Last Update Posted: 2016-03-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 70

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.

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Reference Group	Blood drawing for immune monitoring and questionnaires	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

Primary Outcome Measures

Name	Time	Method
biopsy-confirmed acute rejection incidence	60 weeks

Secondary Outcome Measures

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

Trial Locations

Locations (8)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Charite Campus Virchow-Klinikum; 🇩🇪 Berlin, Germany

University Hospital Regensburg; 🇩🇪 Regensburg, Germany

CHU de Nantes Hotel-Dieu; 🇫🇷 Nantes, France

Guy's Hospital in affiliation with King's College London; 🇬🇧 London, United Kingdom

Churchill Hospital in affiliation with the University of Oxford; 🇬🇧 Oxford, United Kingdom

Ospedale San Raffaele; 🇮🇹 Milan, Italy