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    Summary
    EudraCT Number:2014-002643-18
    Sponsor's Protocol Code Number:REDUCE
    National Competent Authority:Austria - BASG
    Clinical Trial Type:EEA CTA
    Trial Status:Prematurely Ended
    Date on which this record was first entered in the EudraCT database:2018-07-16
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedAustria - BASG
    A.2EudraCT number2014-002643-18
    A.3Full title of the trial
    REDUCE - Multicenter, prospective, randomized study investigating the efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily in comparison to standard triple immunosuppression in senior renal transplant recipients
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    REDUCE - study in a number of european centers for investigation of efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily in comparison to standard therapy with 3 immunosuppressive drugs in senior renal transplant recipients
    A.3.2Name or abbreviated title of the trial where available
    REDUCE
    A.4.1Sponsor's protocol code numberREDUCE
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT02453867
    A.5.4Other Identifiers
    Name:Centre for Evidence in Transplantation ApprovalNumber:CET010
    A.7Trial is part of a Paediatric Investigation Plan No
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorCharité Universitätsmedizin Berlin, Medizinische Klinik m.S. Nephrologie
    B.1.3.4CountryGermany
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportAstellas Europe (unrestricted grant)
    B.4.2CountryUnited Kingdom
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationCharité Universitätsmedizin Berlin
    B.5.2Functional name of contact pointDivision of Nephrology
    B.5.3 Address:
    B.5.3.1Street AddressCharitéplatz 1
    B.5.3.2Town/ cityBerlin
    B.5.3.3Post code10117
    B.5.3.4CountryGermany
    B.5.4Telephone number0049(0)30450514072
    B.5.5Fax number0049(0)30450514902
    B.5.6E-mailsenior.reducetrial@charite.de
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Advagraf 0.5 mg prolonged-release hard capsules
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Prolonged-release capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number0.5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMycophenolate
    D.3.4Pharmaceutical form Capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmofetil mycophenolate
    D.3.9.1CAS number 128794-94-5
    D.3.9.3Other descriptive nameMYCOPHENOLATE MOFETIL
    D.3.9.4EV Substance CodeSUB03360MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationAustria
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameMycophenolate
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMycophenolate sodium
    D.3.9.1CAS number 37415-62-6
    D.3.9.3Other descriptive nameMYCOPHENOLATE SODIUM
    D.3.9.4EV Substance CodeSUB16447MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 4
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationAustria
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNprednisolone
    D.3.9.1CAS number 50-24-8
    D.3.9.3Other descriptive namePREDNISOLONE
    D.3.9.4EV Substance CodeSUB10018MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 5
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Advagraf 1 mg prolonged-release hard capsules
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Prolonged-release capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number1
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 6
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Advagraf 3 mg prolonged-release hard capsules
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Prolonged-release capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number3
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 7
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Advagraf 5 mg prolonged-release hard capsules
    D.2.1.1.2Name of the Marketing Authorisation holderAstellas Pharma Europe B.V
    D.2.1.2Country which granted the Marketing AuthorisationEuropean Union
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Prolonged-release capsule, hard
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNTACROLIMUS
    D.3.9.1CAS number 104987-11-3
    D.3.9.4EV Substance CodeSUB10797MIG
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product Yes
    D.3.11.13.1Other medicinal product typeImmunosuppressant
    D.IMP: 8
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.2Country which granted the Marketing AuthorisationAustria
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation No
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNmethylprednisolone
    D.3.9.1CAS number 83-43-2
    D.3.9.3Other descriptive nameMETHYLPREDNISOLONE
    D.3.9.4EV Substance CodeSUB08872MIG
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Immunosuppression after kidney transplantion in elderly patients ≥65 years of age
    In dieser Studie wird die Immunsuppression bei älteren Nierentransplantierten ≥ 65 Jahre untersucht.
    E.1.1.1Medical condition in easily understood language
    Immunosuppression after kidney transplantion in elderly patients ≥65 years of age
    In dieser Studie wird die Immunsuppression bei älteren Nierentransplantierten ≥ 65 Jahre untersucht.
    E.1.1.2Therapeutic area Not possible to specify
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.1
    E.1.2Level PT
    E.1.2Classification code 10062016
    E.1.2Term Immunosuppression
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level LLT
    E.1.2Classification code 10054990
    E.1.2Term Immunodeficiency secondary to organ transplantation
    E.1.2System Organ Class 10021428 - Immune system disorders
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level HLT
    E.1.2Classification code 10074474
    E.1.2Term Transplantation complications
    E.1.2System Organ Class 100000004863
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To establish efficacy and safety of a reduced immunosuppressive therapy with tacrolimus once daily for senior (>65 years of age) renal transplant recipients.
    Main objective:
    Non-inferiority of a reduced immunosuppressive therapy compared to standard therapy regarding a combined efficacy endpoint (BPAR, graft loss and death) between randomization (at month 3 post-transplant) and month 12 post-transplant
    Die Studie dient zur Untersuchung der Effektivität und Sicherheit einer reduzierten Immunsuppression bei älteren Nierentransplantierten ≥65 Jahre.
    Hauptziel der Studie:
    Nicht-Unterlegenheit eines reduzierten immunsuppressiven Therapieschemas im Vergleich zur Standardtherapie bezogen auf einen kombinierten Effektivitätsendpunkt (BPAR, Transplantatversagen, Tod) von Randomisierung (Monat 3 nach Transplantation) bis Monat 12 nach Transplantation.
    E.2.2Secondary objectives of the trial
    Secondary objectives:
    - Incidence and time of graft loss
    - Incidence and time of death
    - Incidence and time of biopsy proven rejection
    - Evaluation infections: opportunistic (CMV, BKV), severe infections between study groups
    - Evaluation of kidney function by estimation of eGFR (CKD-EPI) between study Groups
    - Evaluation of hospitalisations
    - Evaluation of HLA antibody development and donor specific antibody (DSA) development
    - Evaluation of adverse and severe adverse events
    - Evaluation of post transplant Diabetes mellitus
    - Evaluation of laboratory result bundles (blood counts, etc.)
    - Evaluation of concomittant medication
    - Evaluation of quality of life measures
    - Assessment of Frailty
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    Protocol chapter 4.1.1.
    Inclusion criteria
    1. Males or females, aged ≥65 years and participating in the European SENIOR transplant registry
    2. Patients who received a renal allograft 3 – 3.5 months prior to randomization.
    3. Patient must have received primary or secondary renal allograft from a blood group compatible donor
    4. Standard criteria donors (SCD), expanded criteria donors (ECD), donors after cardiac death (DCD) and living donors (LD) are eligible
    5. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained
    6. Patients on continuous standard triple therapy with tacrolimus once daily (Advagraf®, trough level ≥5ng/ml) in combination with mycophenolate (either ≥1.0g/day MMF or ≥720mg/d EC-MPS) and steroids (≥5mg prednisolone or equivalent) since transplantation
    7. Stable graft function with serum creatinine ≤2.5 mg/dl.
    8. Patients with low to standard immunological risk, who had a PRA below 20% or 20% and no known donor specific antibodies (DSA) at transplantation
    E.4Principal exclusion criteria
    Protocol chapter 4.1.2. Exclusion criteria
    1. Patient with mental dysfunction or inability to comply with the study protocol
    2. Patients, who - according to the investigator - require for medical reasons (e.g. previous rejections) continuous triple therapy or a different tacrolimus exposure
    3. Multi-organ recipients (other solid organ (e.g. pancreas) or bone marrow)
    4. Blood group ABO-incompatible allografts
    5. Patients who suffered from severe T-cell mediated rejection (at least Banff II acute rejection), recurrent acute rejection (>1 episode), or steroid resistant rejection post-transplant
    6. History of antibody-mediated rejection (acute or chronic)
    7. History of rejection 2 months prior to inclusion
    8. Documented presence of donor specific antibodies (DSA) according to local lab results at baseline
    9. Panel reactive antibody (PRA) >20% prior to transplantation, measured according to local standard
    10. Patients receiving or having received Sirolimus, Everolimus, Azathioprine, Belatacept or Cyclophosphamide within 3 months prior to enrolment
    11. Patients having received any other induction therapy than Basiliximab (e.g. depleting polyclonal antithymocyte antibodies (ATG), OKT3, Alemtuzumab)
    12. Patients with proteinuria >1.0 g/day (or >1.0 g/g creatinine) at screening or having experienced nephrotic syndrome due to recurrence of focal segmental glomerulosclerosis (FSGS)
    13. History of alcohol or drug abuse with less than 6 months of sobriety
    14. Patient with a known hereditary immunodeficiency
    15. Patient with active malignancy posttransplant with the exception of local, non-invasive, fully excised, cutaneous basal cell carcinoma, cutaneous squamous cell carcinoma, or cervical carcinoma in situ
    16. Patients with clinically symptomatic congestive heart failure or symptomatic coronary artery disease
    17. Patients with documented (either by serology and/or nuclear acid testing (NAT) clinically active infections (e.g. with a known Hepatitis B, Hepatitis C, HIV, CMV or BK virus infection). Patients who do not have been screened in the previous 6 months, should be screened to confirm seronegativity before enrolment.
    18. Participation in any other investigational clinical trial 3 months before participation in this study, except the SENIOR transplant registry
    19. Patients with leukopenia (<2500 cells/mcl) or neutropenia (<1500 cells/mcl)
    20. Patients with thrombocytopenia (<100 cells/nl)
    21. Patients with liver transaminases or bilirubin values > 3x normal values
    22. Any significant diseases or clinically significant findings, including psychiatric and behavioural problems, medical history and/or physical examination findings that would in the opinion of the investigator preclude the patient from participating in the study.
    23. Patients who have been institutionalized by official or court order
    E.5 End points
    E.5.1Primary end point(s)
    Combined efficacy endpoint (BPAR, graft loss and death) between randomization (month 3 post-transpant) and month 12 posttransplant
    E.5.1.1Timepoint(s) of evaluation of this end point
    Month 12 after transplantation.
    E.5.2Secondary end point(s)
    - Severe after randomization
    - Opportunistic infections after randomization, in particular
    - CMV Infection and CMV Viremia
    - BK Nephropathy and BK Viremia
    - Combined endpoint CMV and BK Viremia
    - Difference in renal function as estimated by the CKD-EPI [34], determined between treatment groups at month 6, 9 and 12 posttransplant.
    - Hospitalisations, hospitalisations for infections and hospitalisations for opportunistic infections (as confirmed by the investigator) after randomization
    - Time to efficacy failure (defined as any patient experiencing death, graft failure, BPAR) after randomization
    - Incidence and time of BPAR and/or graft loss, of graft loss and/or death, graft loss alone, death alone
    - Incidence and time to BPAR (Banff grade of at least IA) and Borderline rejection(s) after randomization according to BANFF classes 2013
    - Incidence and time to clinically suspected and treated rejection episodes (treated acute rejection despite the absence of confirmatory evidence on a biopsy) and to steroid-resistant rejections, recurrent rejections, antibody-treated rejections and antibody-mediated acute rejection after randomization
    - Proportion of severity grades of the first episode of BPAR (Banff grade) occurring after randomization
    - Development of circulating anti-HLA-antibodies, non HLA-antibodies and/or de novo donor specific antibodies (DSA)
    - Change of renal function (according to CKD-EPI formula) from randomization to month 12 after transplantation.
    - Comparison of the GFR-slope between randomization and month 12 (according to CKD-EPI-formula) between groups
    - Incidence of patients with different stages of chronic kidney disease (CKD) according to CKD-EPI formula and with suboptimal GFR (<60ml/min, <45ml/min and <30 ml/min according to CKD-EPI formula)
    - Comparison of the incidence of patients with improved renal function compared to baseline at randomization
    - Differences between treatment groups after randomization with respect to the incidence of adverse events (AEs), serious Adverse events (SAEs), predefined AEs, vital signs and potentially clinically significant laboratory measures
    - Incidence of any malignancy and infection after randomization
    - Differences of hospitalisation days between treatment groups after randomization and in hospitalisation days due to infections and opportunistic infections (as confirmed by the investigator) between treatment groups after randomization
    - Incidence and time to premature discontinuation of randomly assigned treatment (as confirmed by the investigator) for any reason
    - Comparison of reasons for treatment discontinuation or treatment changes (as confirmed by the investigator)
    - Incidence of posttransplant diabetes (PTDM) at month 12 as defined by need for any antidiabetic agent (oral or insulin) and/or HbA1c >48 mmol/mol (>6,5%) in a patient with no prior medical history of diabetes before transplantation and of posttransplant hyperglycemia within 9 months after randomization as defined by a fasting plasma glucose ≥126 mg/dL, and/or afternoon capillary glucose ≥200mg/dl with or without insulin requirement or need for an oral antidiabetic agent in a patient with no prior medical history of diabetes
    - Incidences of Hb1Ac elevation a) >42 mmol/mol (>6.0%), b) >48 mmol/mol (>6,5%) and c) >53 mmol/mol (>7.0% ) at month 12 post transplantation
    - Differences in the parameters of glucose control including HbA1c and blood lipids (total Cholesterol, LDL, HDL, Trigylcrides)
    - Difference in blood pressure and blood pressure medication
    - Difference in cardiovascular events defined as any cardiac event, stroke or peripheral vascular disease including invasive therapeutic cardiovascular interventions after randomization
    - Difference in cardiovascular risk as estimated by the cardiovascular risk calculator for renal transplant recipients[35]
    - Difference in the incidence of anemia as reported as adverse events, or the use of erythropoietin stimulating agents, or haemoglobin value <10g/dl after randomization and at month 12 posttransplant
    - Difference in the use of erythropoietin stimulating agents after randomization and at month 12 posttransplant
    - Incidence of patients with a low haemoglobin <10.0g/dl, or <11g/dl at month 12 after transplantation
    - Difference in leucocyte and neutrophil counts at 12 months after transplantation
    - Difference in the incidence of leucopenia (<3,5/nl) and neutropenia (<1,5/nl) and the use of colony stimulating factors after randomization and of patients with a leucopenia <4,0/nl, <3,0/nl or <2,5/nl after randomization
    - IgG levels
    - Incidence of Bone disease and/ fractures as confirmed by the investigator, differences in height between groups
    - Assessment of frailty
    - Evaluation and comparison of quality of life (as assessed by PROMIS Profile 29 questionnaire) and medical symptom burden (as assessed by MTSODS questionnaire) between groups at month 3 and 12 posttransplant


    E.5.2.1Timepoint(s) of evaluation of this end point
    Month 12 after transplantation
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) No
    E.7.4Therapeutic use (Phase IV) Yes
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Yes
    E.8.1.3Single blind No
    E.8.1.4Double blind No
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo No
    E.8.2.3Other Yes
    E.8.2.3.1Comparator description
    Combination of tacrolimus (Advagraf), mycophenolate, steroids
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned2
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA43
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA No
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LVLS - The study ends when the last data element is available from the last subject to complete the month 12 visit.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years4
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years4
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) No
    F.1.1.5Children (2-11years) No
    F.1.1.6Adolescents (12-17 years) No
    F.1.2Adults (18-64 years) No
    F.1.3Elderly (>=65 years) Yes
    F.1.3.1Number of subjects for this age range: 400
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception No
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally No
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state20
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 400
    F.4.2.2In the whole clinical trial 400
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    All patients will be followed up yearly in the SENIOR registry for up to 10 years. The SENIOR registry is registered at ClinicalTrials.gov: NCT02558452. This registry is built to observe 1000 elderly european kidney transplant recipients ≥65 years of age from Transplantation for 10 years. Thereafter the patients will stay within the follow up programs of each transplantation Center.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2018-08-02
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2018-12-07
    P. End of Trial
    P.End of Trial StatusPrematurely Ended
    P.Date of the global end of the trial2020-08-03
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