NCT01656135

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.

Trial Health

93
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
70

participants targeted

Target at P25-P50 for phase_4

Timeline
Completed

Started Dec 2012

Typical duration for phase_4

Geographic Reach
5 countries

8 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 31, 2012

Completed
2 days until next milestone

First Posted

Study publicly available on registry

August 2, 2012

Completed
4 months until next milestone

Study Start

First participant enrolled

December 1, 2012

Completed
3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2015

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2015

Completed
Last Updated

March 9, 2016

Status Verified

March 1, 2016

Enrollment Period

3 years

First QC Date

July 31, 2012

Last Update Submit

March 8, 2016

Conditions

End-stage Renal FailureKidney Graft Rejection

Keywords

gold standard treatmentimmune monitoringacute rejectiongraft rejectionliving-donorrenal transplantationkidney transplantation

Outcome Measures

Primary Outcomes (1)

  • biopsy-confirmed acute rejection incidence

    60 weeks

Secondary Outcomes (9)

  • 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

  • +4 more secondary outcomes

Other Outcomes (2)

  • Immune Monitoring (IM) assessment

    60 weeks

  • Health Economics (HEC) assessment

    60 weeks

Study Arms (1)

Reference Group

OTHER

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

Interventions

Blood drawing for immune monitoring and questionnairesOTHER
Reference Group

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Organ Donor:
  • 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.

You may not qualify if:

  • 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
  • +14 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (8)

University of California San Francisco

San Francisco, California, 94143, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

CHU de Nantes Hotel-Dieu

Nantes, 44093, France

Location

Charite Campus Virchow-Klinikum

Berlin, 13353, Germany

Location

University Hospital Regensburg

Regensburg, 93053, Germany

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Guy's Hospital in affiliation with King's College London

London, SE1 9RT, United Kingdom

Location

Churchill Hospital in affiliation with the University of Oxford

Oxford, OX3 7LE, United Kingdom

Location

Related Publications (3)

  • Sly LM, McKay DM. Macrophage immunotherapy: overcoming impediments to realize promise. Trends Immunol. 2022 Dec;43(12):959-968. doi: 10.1016/j.it.2022.10.002. Epub 2022 Oct 29.

    PMID: 36441083DERIVED

  • Moreau A, Kervella D, Bouchet-Delbos L, Braudeau C, Saiagh S, Guerif P, Limou S, Moreau A, Bercegeay S, Streitz M, Sawitzki B, James B, Harden PN, Game D, Tang Q, Markmann JF, Roberts ISD, Geissler EK, Dreno B, Josien R, Cuturi MC, Blancho G; DIVAT consortium. A Phase I/IIa study of autologous tolerogenic dendritic cells immunotherapy in kidney transplant recipients. Kidney Int. 2023 Mar;103(3):627-637. doi: 10.1016/j.kint.2022.08.037. Epub 2022 Oct 26.

    PMID: 36306921DERIVED

  • 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.

    PMID: 32446407DERIVED

Related Links

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Blood Specimen CollectionMonitoring, ImmunologicSurveys and Questionnaires

Condition Hierarchy (Ancestors)

Renal Insufficiency, ChronicRenal InsufficiencyKidney DiseasesUrologic DiseasesFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesMale Urogenital DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen HandlingClinical Laboratory TechniquesDiagnostic Techniques and ProceduresDiagnosisPuncturesSurgical Procedures, OperativeInvestigative TechniquesImmunologic TestsMonitoring, PhysiologicImmunologic TechniquesData CollectionEpidemiologic MethodsHealth Care Evaluation MechanismsQuality of Health CareHealth Care Quality, Access, and EvaluationPublic HealthEnvironment and Public Health

Study Officials

  • Edward K. Geissler, Ph.D.

    University of Regensburg

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
NA
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Chief Investigator and EU Project Leader

Study Record Dates

First Submitted

July 31, 2012

First Posted

August 2, 2012

Study Start

December 1, 2012

Primary Completion

December 1, 2015

Study Completion

December 1, 2015

Last Updated

March 9, 2016

Record last verified: 2016-03

Locations

FR(1)US(2)DE(2)GB(2)IT(1)