The ONE Study M Reg Trial (ONEmreg12)
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| ClinicalTrials.gov Identifier: NCT02085629 |
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Recruitment Status :
Terminated
(Insufficient rate of patient recruitment and treatment.)
First Posted : March 13, 2014
Last Update Posted : April 18, 2019
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Renal Failure, End Stage | Biological: Donor M reg (Mreg_UKR) | Phase 1 Phase 2 |
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.
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 8 participants |
| Allocation: | N/A |
| Intervention Model: | Single Group Assignment |
| Masking: | None (Open Label) |
| Primary Purpose: | Treatment |
| Official Title: | The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - M Reg Trial |
| Actual Study Start Date : | July 24, 2014 |
| Actual Primary Completion Date : | December 3, 2018 |
| Actual Study Completion Date : | December 3, 2018 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: M reg treatment
Donor M reg (2.5-7.5 million cells/kg) IV infused (6-7d before Tx) into recipients of a LD renal Tx. Recipients also receive prednisolone, mycophenolate mofetil and tacrolimus, as detailed below: Prednisolone
MMF (or biologic equiv.)
Tacrolimus (or biologic equiv.)
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Biological: Donor M reg (Mreg_UKR)
Experimental: M reg treatment Donor M reg (2.5-7.5 million cells/kg) IV infused (6-7d before Tx) into recipients of a living donor renal Tx. Recipients also receive prednisolone, mycophenolate mofetil and tacrolimus background immunosuppression (as described in detail in the arm description). |
- biopsy-confirmed acute rejection incidence [ Time Frame: 60 weeks ]
- 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
- incidence of malignancies arising directly from Mreg_UKR [ Time Frame: 60 weeks ]
- incidence of autoimmune disorders [ Time Frame: 60 weeks ]
- incidence of inflammatory pathologies [ Time Frame: 60 weeks ]
- incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney [ Time Frame: 60 weeks ]
- A Health-Economics Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures [ Time Frame: 60 weeks ]this subproject will also calculate the cost-effectiveness of the Mreg_UKR cell product
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, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
RECIPEINT
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
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
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
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02085629
| Germany | |
| University Hospital Regensburg | |
| Regensburg, Germany, 93053 | |
| Study Director: | Edward K Geissler, PhD | University Hospital Regensburg, University of Regensburg | |
| Principal Investigator: | Bernhard Banas, MD | University Hospital Regensburg, University of Regensburg | |
| Principal Investigator: | James A Hutchinson, MD, PhD | University Hospital Regensburg, University of Regensburg |
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Edward Geissler, Professor, University of Regensburg |
| ClinicalTrials.gov Identifier: | NCT02085629 |
| Other Study ID Numbers: |
ONEmreg12 2013-000999-15 ( EudraCT Number ) grant number 260687 ( Other Grant/Funding Number: European Union FP7 Programme ) |
| First Posted: | March 13, 2014 Key Record Dates |
| Last Update Posted: | April 18, 2019 |
| Last Verified: | April 2019 |
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renal failure, end stage renal transplantation cell therapy macrophages, monocyte derived |
immune tolerance ONE Study immunotherapy |
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Renal Insufficiency Kidney Failure, Chronic Kidney Diseases Urologic Diseases Renal Insufficiency, Chronic |