<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02252055</url>
  </required_header>
  <id_info>
    <org_study_id>RC13_0441</org_study_id>
    <nct_id>NCT02252055</nct_id>
  </id_info>
  <brief_title>The ONE Study ATDC Trial</brief_title>
  <acronym>ONEatDC</acronym>
  <official_title>A Phase I/II Monocentric Trial of Cellular Immunotherapy Based on Autologous Tolerogenic Dendritic Cells (ATDCs) Administration in Patients With Renal Insufficiency Receiving as First Transplantation a Kidney Transplant From a Living-donor.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nantes University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nantes University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To collect evidence of the safety of administering autologous tolerogenic dendritic cells&#xD;
      (ATDC) preparations to living-donor renal transplant recipients in the context of an&#xD;
      international European Union funded consortium aimed at evaluationg cellular immunotherapy in&#xD;
      solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced&#xD;
      by ATDC therapy can evntually be used to reduce the need for conventional immunosuppression&#xD;
      in transplant recipients.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Decades of immunosuppressive drug development have produced an array of powerful&#xD;
      pharmacological agents, but the various drawbacks associated with these treatments leaves&#xD;
      considerable room for improvement. By harnessing the power of suppressive mechanisms in the&#xD;
      human immune system, regulatory cell therapy may be able to support peripheral tolerance and&#xD;
      induce a level of donor-specific unresponsiveness that allows for a reduction in the use of&#xD;
      conventional immunosuppression in organ transplant recipients. Several alternative regulatory&#xD;
      cell types have been identified as potential adjunct immunotherapies for solid organ&#xD;
      transplantation and are now approaching a stage of development that would allow clinical&#xD;
      testing in an early-stage trial. The ONE Study aims to answer the question as whether ATDC&#xD;
      treatment, or immunoregulatory cell-based therapy in general, has any place in the clinical&#xD;
      management of solid organ transplant recipients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 19, 2015</start_date>
  <completion_date type="Actual">November 14, 2018</completion_date>
  <primary_completion_date type="Actual">November 14, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence of biopsy-confirmed acute rejection (BCAR)</measure>
    <time_frame>60 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to first acute rejection episode</measure>
    <time_frame>60 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severity of acute rejection episodes</measure>
    <time_frame>60 weeks</time_frame>
    <description>based on response to treatment and histological scoring</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Total immunosuppressive burden</measure>
    <time_frame>60 weeks</time_frame>
    <description>assessed at last study visit</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings</measure>
    <time_frame>60 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Prevention of chronic graft dysfunction (chronic rejection or IF/TA)</measure>
    <time_frame>60 weeks</time_frame>
    <description>assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection (acute or chronic).</measure>
    <time_frame>60 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Avoidance of drug-related complications by immunosuppressant reduction</measure>
    <time_frame>60 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of embolic pulmonary complications and other embolic events</measure>
    <time_frame>60 weeks</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure</measure>
    <time_frame>1 week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Biochemical disturbances caused by cell infusion</measure>
    <time_frame>1 week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus</measure>
    <time_frame>1 week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Over-suppression of the immune system assessed by the incidence of neoplasia.</measure>
    <time_frame>1 week</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Immunological condition of study patients w</measure>
    <time_frame>60 weeks</time_frame>
    <description>an extensive immune monitoring program has been established in the ONE Study</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Incidence of malignancies arising directly from ATDC_Nantes</measure>
    <time_frame>60 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>ii) incidence of autoimmune disorders</measure>
    <time_frame>60 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of inflammatory pathologies</measure>
    <time_frame>60 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney.</measure>
    <time_frame>60 weeks</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>A Health-Economic Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures.</measure>
    <time_frame>60weeks</time_frame>
    <description>This subproject will also calculate the cost-effectiveness of ATDC_Nantes to review the financial implications of cellular immunotherapy as a practical and routine clinical prescription.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>Renal Failure, End Stage</condition>
  <arm_group>
    <arm_group_label>ATDC Treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation.&#xD;
Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus, as detailed below :&#xD;
Prednidolone :&#xD;
D 0: 500 mg IV&#xD;
D 1: 125 mg IV&#xD;
D 2 to 14: 20.0 mg/d&#xD;
Wk 3 to 4: 15.0 mg/d&#xD;
Wk 5 to 8: 10.0 mg/d&#xD;
Wk 9 to 12: 5.0 mg/d&#xD;
Wk 13 to 14: 2.5 mg/d&#xD;
Wk 15 to End:Cessation&#xD;
MMF (or biologic equiv.):&#xD;
D -7 to -2: 500 mg/d (250mg 2x/d)&#xD;
D -1 to 14: 2000 mg/d&#xD;
Wk 3 to 36: 1000 mg/d&#xD;
Wk 37 to 40: 750 mg/d&#xD;
Wk 41 to 44: 500 mg/d&#xD;
Wk 45 to 48: 250 mg/d&#xD;
Wk 49 to End:Cessation Note : MMF tapering will only happen if the 36-week protocol biopsy shows no signs of subclinical rejection and there is evidence of declining renal function or if the clinician has any other concern about MMF dose reduction.&#xD;
Tacrolimus :&#xD;
≤ 48 h pre-Tx to D 14: 3-12 ng/ml&#xD;
Wk 3 to 12: 3-10 ng/ml&#xD;
Wk 13 to 36: 3-8 ng/ml&#xD;
Wk 37 to End: 3-6 ng/ml</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>ATDC_Nantes</intervention_name>
    <description>ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation into recipients also recipients of a living donor renal transplantation.&#xD;
Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus background immunosuppression ( as described in detail in the arm description)</description>
    <arm_group_label>ATDC Treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        RECIPIENT&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Chronic renal insufficiency necessitating kidney transplantation and approved to&#xD;
             receive a primary kidney allograft from a living donor&#xD;
&#xD;
          2. Aged at least 18 years&#xD;
&#xD;
          3. Able to commence the immunosuppressive regimen at the protocol-specified time point&#xD;
&#xD;
          4. Willing and able to participate in The ONE Study IM and HEC subprojects&#xD;
&#xD;
          5. Eligible for leucapheresis prior to organ transplantation&#xD;
&#xD;
          6. Signed and dated written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patient has previously received any tissue or organ transplant other than the planned&#xD;
             kidney graft&#xD;
&#xD;
          2. Known contraindication to the protocol-specified treatments / medications (like known&#xD;
             allergies to heparin)&#xD;
&#xD;
          3. Genetically identical to the prospective organ donor at the HLA loci (A.B.DR 0&#xD;
             mismatch)&#xD;
&#xD;
          4. PRA grade &gt; 0 within 6 months prior to enrolment&#xD;
&#xD;
          5. Previous treatment with any desensitisation procedure (with or without IVIg)&#xD;
&#xD;
          6. Concomitant malignancy or history of malignancy within 5 years prior to planned study&#xD;
             entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of&#xD;
             the skin)&#xD;
&#xD;
          7. ABO incompatibility&#xD;
&#xD;
          8. Presence of DSA (donor specific antibodies) detected by luminex prior transplantation&#xD;
&#xD;
          9. Evidence of significant local or systemic infection&#xD;
&#xD;
         10. HIV-positive, EBV-negative or suffering chronic viral hepatitis, syphilis serology-&#xD;
             positive&#xD;
&#xD;
         11. Significant liver disease, defined as persistently elevated AST and/or ALT levels &gt; 2&#xD;
             x ULN (Upper Limit of Normal range)&#xD;
&#xD;
         12. Malignant or pre-malignant haematological conditions&#xD;
&#xD;
         13. Any uncontrolled medical condition or concurrent disease that could interfere with the&#xD;
             study objectives&#xD;
&#xD;
         14. Any condition which, in the judgement of the Investigator, would place the subject at&#xD;
             undue risk&#xD;
&#xD;
         15. Ongoing treatment with systemic immunosuppressive drugs at inclusion (despite&#xD;
             corticoids lower than 10 mg)&#xD;
&#xD;
         16. Participation in another clinical trial during the study or within 28 days prior to&#xD;
             planned study entry&#xD;
&#xD;
         17. Exposure to an investigational product during the study or within 28 days prior to&#xD;
             planned study entry&#xD;
&#xD;
         18. Female patients of child-bearing potential with a positive pregnancy test at enrolment&#xD;
             and F01&#xD;
&#xD;
         19. Female patients who are breast-feeding&#xD;
&#xD;
         20. All female patients of child-bearing potential* UNLESS:&#xD;
&#xD;
               1. The patient is willing to maintain a highly effective method of birth control**&#xD;
                  for the duration of the study&#xD;
&#xD;
               2. The career, lifestyle, or sexual orientation of the patient ensures that there is&#xD;
                  no risk of pregnancy for the duration of the study (at the discretion of the&#xD;
                  Investigator)&#xD;
&#xD;
         21. Psychological, familial, sociological or geographical factors potentially hampering&#xD;
             compliance with the study protocol and follow-up visit schedule&#xD;
&#xD;
         22. Any form of substance abuse, psychiatric disorder, or other condition that, in the&#xD;
             opinion of the Investigator, may invalidate communication with the Investigator and/or&#xD;
             designated study personnel&#xD;
&#xD;
         23. Patients unable to freely give their informed consent (e.g. individuals under legal&#xD;
             guardianship).&#xD;
&#xD;
             Criteria specific to the infusion of the ATDC_Nantes:&#xD;
&#xD;
         24. Any pro-coagulant disposition, as evidenced by a past history of thromboembolic&#xD;
             disease or abnormal laboratory coagulation parameters which, in the judgement of the&#xD;
             Investigator, would place the subject at undue risk&#xD;
&#xD;
         25. Any condition resulting in a substantial reduction in the volume of the pulmonary&#xD;
             vasculature or an increase in the pulmonary vascular resistance. Any disease or&#xD;
             disease process leading to substantially elevated pulmonary arterial pressure (as&#xD;
             evidenced by electrocardiography, echocardiography, radiology or cardiac&#xD;
             catheterisation) or right heart hypertrophy or dysfunction&#xD;
&#xD;
         26. Known atrial or ventricular septal defects posing a risk of paradoxical embolism of&#xD;
             infused cells or cell aggregates&#xD;
&#xD;
         27. Known hypersensitivity to any component of the cell product or components used in the&#xD;
             manufacture of the cell product.&#xD;
&#xD;
        DONOR&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Eligible for live kidney donation&#xD;
&#xD;
          2. Willing and able to provide a blood sample for The ONE Study IM Subproject&#xD;
&#xD;
          3. Willing to provide personal and medical/biological data for the trial analysis&#xD;
&#xD;
          4. Signed and dated written informed consent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Genetically identical to the prospective organ recipient at the HLA loci (A.B.DR 0&#xD;
             mismatch)&#xD;
&#xD;
          2. Exposure to any investigational agents at the time of kidney donation, or within 28&#xD;
             days prior to kidney donation&#xD;
&#xD;
          3. Any form of substance abuse, psychiatric disorder, or other condition that, in the&#xD;
             opinion of the Investigator, may invalidate communication with the Investigator and/or&#xD;
             designated study personnel&#xD;
&#xD;
          4. Subjects unable to freely give their informed consent (e.g. individuals under legal&#xD;
             guardianship).&#xD;
&#xD;
          5. ABO incompatibility&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edward K Geissler, PhD</last_name>
    <role>Study Director</role>
    <affiliation>University Hospital Regensburg</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nantes University hospital</name>
      <address>
        <city>Nantes</city>
        <zip>44093</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <link>
    <url>http://www.onestudy.org</url>
    <description>Related Info</description>
  </link>
  <reference>
    <citation>Geissler EK. The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res. 2012 Sep 28;1(1):11. doi: 10.1186/2047-1440-1-11. No abstract available.</citation>
    <PMID>23369457</PMID>
  </reference>
  <verification_date>December 2018</verification_date>
  <study_first_submitted>September 25, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 29, 2014</study_first_posted>
  <last_update_submitted>December 28, 2018</last_update_submitted>
  <last_update_submitted_qc>December 28, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">January 2, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Failure, Chronic</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02252055
org study id: RC13_0441
nct id: NCT02252055
lead sponsor: 
has dmc: Yes
To collect evidence of the safety of administering autologous tolerogenic dendritic cells
      (ATDC) preparations to living-donor renal transplant recipients in the context of an
      international European Union funded consortium aimed at evaluationg cellular immunotherapy in
      solid organ transplantation (The ONE Study). It is anticipated that immune regulation induced
      by ATDC therapy can evntually be used to reduce the need for conventional immunosuppression
      in transplant recipients.
Decades of immunosuppressive drug development have produced an array of powerful
      pharmacological agents, but the various drawbacks associated with these treatments leaves
      considerable room for improvement. By harnessing the power of suppressive mechanisms in the
      human immune system, regulatory cell therapy may be able to support peripheral tolerance and
      induce a level of donor-specific unresponsiveness that allows for a reduction in the use of
      conventional immunosuppression in organ transplant recipients. Several alternative regulatory
      cell types have been identified as potential adjunct immunotherapies for solid organ
      transplantation and are now approaching a stage of development that would allow clinical
      testing in an early-stage trial. The ONE Study aims to answer the question as whether ATDC
      treatment, or immunoregulatory cell-based therapy in general, has any place in the clinical
      management of solid organ transplant recipients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Incidence of biopsy-confirmed acute rejection (BCAR)
time frame: 60 weeks
measure: Time to first acute rejection episode
time frame: 60 weeks
measure: Severity of acute rejection episodes
time frame: 60 weeks
description: based on response to treatment and histological scoring
measure: Total immunosuppressive burden
time frame: 60 weeks
description: assessed at last study visit
measure: Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings
time frame: 60 weeks
measure: Prevention of chronic graft dysfunction (chronic rejection or IF/TA)
time frame: 60 weeks
description: assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.
measure: Incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection (acute or chronic).
time frame: 60 weeks
measure: Avoidance of drug-related complications by immunosuppressant reduction
time frame: 60 weeks
measure: Incidence of embolic pulmonary complications and other embolic events
time frame: 60 weeks
measure: Incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure
time frame: 1 week
measure: Biochemical disturbances caused by cell infusion
time frame: 1 week
measure: Over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus
time frame: 1 week
measure: Over-suppression of the immune system assessed by the incidence of neoplasia.
time frame: 1 week
measure: Immunological condition of study patients w
time frame: 60 weeks
description: an extensive immune monitoring program has been established in the ONE Study
measure: Incidence of malignancies arising directly from ATDC_Nantes
time frame: 60 weeks
measure: ii) incidence of autoimmune disorders
time frame: 60 weeks
measure: Incidence of inflammatory pathologies
time frame: 60 weeks
measure: Incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney.
time frame: 60 weeks
measure: A Health-Economic Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures.
time frame: 60weeks
description: This subproject will also calculate the cost-effectiveness of ATDC_Nantes to review the financial implications of cellular immunotherapy as a practical and routine clinical prescription.
arm group label: ATDC Treatment
arm group type: Experimental
description: ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation.
Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus, as detailed below :
Prednidolone :
D 0: 500 mg IV
D 1: 125 mg IV
D 2 to 14: 20.0 mg/d
Wk 3 to 4: 15.0 mg/d
Wk 5 to 8: 10.0 mg/d
Wk 9 to 12: 5.0 mg/d
Wk 13 to 14: 2.5 mg/d
Wk 15 to End:Cessation
MMF (or biologic equiv.):
D -7 to -2: 500 mg/d (250mg 2x/d)
D -1 to 14: 2000 mg/d
Wk 3 to 36: 1000 mg/d
Wk 37 to 40: 750 mg/d
Wk 41 to 44: 500 mg/d
Wk 45 to 48: 250 mg/d
Wk 49 to End:Cessation Note : MMF tapering will only happen if the 36-week protocol biopsy shows no signs of subclinical rejection and there is evidence of declining renal function or if the clinician has any other concern about MMF dose reduction.
Tacrolimus :
≤ 48 h pre-Tx to D 14: 3-12 ng/ml
Wk 3 to 12: 3-10 ng/ml
Wk 13 to 36: 3-8 ng/ml
Wk 37 to End: 3-6 ng/ml
intervention type: Biological
intervention name: ATDC_Nantes
description: ATDC treatment (1 x 106 cells/kg BW slow peripheral venous) occurs the day before transplantation into recipients also recipients of a living donor renal transplantation.
Recipients also receive prednisolone, Mycophenolate Mofetil and tacrolimus background immunosuppression ( as described in detail in the arm description)
arm group label: ATDC Treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Edward K Geissler, PhD
role: Study Director
affiliation: University Hospital Regensburg
facility: 
country: France
url: http://www.onestudy.org
description: Related Info
citation: Geissler EK. The ONE Study compares cell therapy products in organ transplantation: introduction to a review series on suppressive monocyte-derived cells. Transplant Res. 2012 Sep 28;1(1):11. doi: 10.1186/2047-1440-1-11. No abstract available.
PMID: 23369457
responsible party type: Sponsor
mesh term: Kidney Failure, Chronic