Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00006374

Trial Description

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Title

The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - M Reg Trial

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Trial Acronym

ONEmreg12

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URL of the Trial

[---]*

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Brief Summary in Lay Language

To collect evidence of the safety of administering donor-derived regulatory macrophage (M
reg) preparations to living-donor renal transplant recipients in the context of an
international European Union funded consortium aimed at evaluating cellular immunotherapy in
solid organ transplantation (The ONE Study). It is anticipated that immune regulation
induced by M reg therapy can eventually be used to reduce the need for conventional
immunosuppression in transplant recipients.

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Brief Summary in Scientific Language

Decades of immunosuppressive drug development has 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 EU-funded international ONE Study consortium
aims to answer the question as to whether M reg treatment, or other immunoregulatory
cell-based therapies, can be advanced in the clinical management of solid organ transplant
recipients.

This particular M reg trial aims to explore the potential of M reg therapy as an adjunct
immunosuppressive treatment in living-donor renal transplant recipients through a clinical
protocol design shared by other investigators in The ONE Study group testing additional
regulatory cell therapies in separate trials.

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Organizational Data

  •   DRKS00006374
  •   2015/04/10
  •   2014/03/10
  •   yes
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Secondary IDs

  •   2013-000999-15 
  •   NCT02085629  (ClinicalTrials.gov)
  •   ONEmreg12  (University of Regensburg)
  •   2013-000999-15 
  •   grant number 260687 
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Health Condition or Problem studied

  •   Renal Failure, End Stage
  •   N18.5 -  Chronic kidney disease, stage 5
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Interventions/Observational Groups

  •   Biological: Donor M reg (Mreg_UKR)
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Characteristics

  •   Interventional
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  •   Single arm study
  •   Open (masking not used)
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  •   Uncontrolled/Single arm
  •   Treatment
  •   Single (group)
  •   I-II
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Primary Outcome

- biopsy-confirmed acute rejection incidence; time frame: 60 weeks

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Secondary Outcome

- time to first acute rejection episode; time frame: 60 weeks
- severity of acute rejection episodes; time frame: 60 weeks; based on response to treatment and histological scoring
- total immunosuppressive burden; time frame: 60 weeks; assessed at last study visit
- incidence of patients treated for subclinical acute rejection; time frame: 60 weeks
- prevention of chronic graft dysfunction (chronic rejection or IF/TA); time frame: 60 weeks; assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures
- incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection; time frame: 60 weeks
- avoidance of drug-related complications by immunosuppressant reduction; time frame: 60 weeks; assessed by the incidence of reported adverse drug reactions
- incidence of embolic pulmonary complications and other embolic events; time frame: 60 weeks
- incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure; time frame: 1 week
- biochemical disturbances caused by cell infusion; time frame: 1 week
- over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus; time frame: 60 weeks
- over-suppression of the immune system assessed by the incidence of neoplasia; time frame: 60 weeks
- immunological condition of study patients; time frame: 60 weeks; an extensive immune monitoring program has been established in The ONE Study

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Countries of Recruitment

  •   Germany
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Locations of Recruitment

  •  
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Recruitment

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  •   2014/07/31
  •   16
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   no maximum age
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Additional Inclusion Criteria

- Chronic renal insufficiency necessitating kidney Tx

- Aged at least 18 years

- Able to commence the immunosuppressive regimen as specified

- Willing and able to participate in The ONE Study subprojects

- Signed and dated written informed consent

DONOR

Inclusion Criteria:

- Eligible for live kidney donation

- Aged at least 18 years

- Willing and able to provide a blood sample for The ONE Study Subproject

- Willing to provide personal and medical/biological data for the trial analysis

- Eligible for leucapheresis prior to organ donation

- Signed and dated written informed consent

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Exclusion Criteria

- Patient has previously received any tissue or organ Tx

- Known contraindication to the protocol-specified treatments /medications

- HLA 0-0-0 mismatch

- PRA grade >40% within 6 mo. prior to enrolment

- Previous desensitisation treatment

- Concomitant malignancy or history of malignancy <5 years before study entry
(excluding successfully-treated non-metastatic skin BCC or SCC)

- Significant local or systemic infection

- HIV-positive, EBV-negative or suffering chronic viral hepatitis

- CMV negative and receiving a kidney from a CMV+ donor

- Significant liver disease

- Malignant or pre-malignant haematological conditions

- Any uncontrolled condition that could interfere with study objectives

- Any condition placing the subject at undue risk

- Ongoing treatment with systemic immunosuppressive drugs at study entry

- Exposure to an investigational product during the study, or within 28 days or 5
half-lives of the product before study entry

- Female patients of child-bearing potential with a +pregnancy test

- Female patients breast-feeding or that are of child bearing potential and unwilling
to use effective birth control

- Psychological, familial, sociological or geographical factors hampering compliance

- Any substance abuse or psychiatric disorder

- Patients unable to freely give informed consent

- Known IgA or IgG deficiency

- Any pro-coagulant disposition causing undue risk

- Previous history of transfusion-associated disease causing undue risk

- Conditions resulting in substantially reduced pulmonary vasculature or increased
pulmonary vascular resistance. Diseases causing substantially elevated pulmonary
arterial or right heart hypertrophy or dysfunction

- Known atrial or ventricular septal defects posing a risk of embolism

- Known hypersensitivity to components of the manufactured cell product

DONOR

Exclusion Criteria:

- Genetically identical to the prospective organ recipient at the HLA loci (0-0-0
mismatch)

- CMV-positive and donating to a CMV-negative recipient

- Exposure to an investigational product during the study, or within 28 days or 5
half-lives of the product before study entry

- 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

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Addresses

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    • University of Regensburg
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    • University Hospital Regensburg, University of Regensburg
    • Edward K Geissler, PhD 
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    • Edward K Geissler, PhD 
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

  •   ONE Study
  •   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.; 23369457
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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/11/05
* This entry means the parameter is not applicable or has not been set.