Reference Group Trial for The ONE Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
European Commission
Information provided by (Responsible Party):
Edward Geissler, University of Regensburg
ClinicalTrials.gov Identifier:
NCT01656135
First received: July 31, 2012
Last updated: October 20, 2014
Last verified: October 2014
  Purpose

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 Intervention Phase
End-stage Renal Failure
Kidney Graft Rejection
Other: Blood drawing for immune monitoring and questionnaires
Phase 4

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Regensburg:

Primary Outcome Measures:
  • biopsy-confirmed acute rejection incidence [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • time to first acute rejection episode [ Time Frame: within 60 weeks ] [ Designated as safety issue: No ]
  • severity of acute rejection episodes [ Time Frame: within 60 weeks ] [ Designated as safety issue: No ]
  • total immunosuppressive burden [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of chronic graft dysfunction [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of graft loss through rejection [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of adverse drug reactions [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of major infections [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of neoplasia [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • incidence of patients treated for subclinical acute rejection [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]

Other Outcome Measures:
  • Immune Monitoring (IM) assessment [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]
  • Health Economics (HEC) assessment [ Time Frame: 60 weeks ] [ Designated as safety issue: No ]

Enrollment: 70
Study Start Date: December 2012
Estimated Study Completion Date: December 2015
Estimated Primary Completion Date: December 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01656135

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

Additional Information:
No publications provided

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, 2011-004301-24
Study First Received: July 31, 2012
Last Updated: October 20, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
Germany: Federal Institute for Drugs and Medical Devices
Italy: National Monitoring Centre for Clinical Trials - Ministry of Health

Keywords provided by University of Regensburg:
gold standard treatment
immune monitoring
acute rejection
graft rejection
living-donor
renal transplantation
kidney transplantation

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Kidney Diseases
Renal Insufficiency, Chronic
Urologic Diseases

ClinicalTrials.gov processed this record on October 23, 2014