The ONE Study M Reg Trial

Renal Failure, End Stage Clinical Trial

— ONEmreg12  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02085629
• Other study ID #: ONEmreg12
• Secondary ID: 2013-000999-15gr
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: July 24, 2014
• Est. completion date: December 3, 2018

Study information

• Verified date: April 2019
• Source: University of Regensburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 8
• Est. completion date: December 3, 2018
• Est. primary completion date: December 3, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Kidney Failure, Chronic
• Renal Failure, End Stage
• Renal Insufficiency

Intervention

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).

Locations

Country	Name	City	State
Germany	University Hospital Regensburg	Regensburg

Sponsors (1)

Lead Sponsor	Collaborator
University of Regensburg

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	incidence of malignancies arising directly from Mreg_UKR		60 weeks
Other	incidence of autoimmune disorders		60 weeks
Other	incidence of inflammatory pathologies		60 weeks
Other	incidence of anaemia, cytopaenia or biochemical disturbances unrelated to the function of the transplanted kidney		60 weeks
Other	A Health-Economics Subproject will evaluate the health-related quality-of-life of trial patients using patient-reported outcome measures	this subproject will also calculate the cost-effectiveness of the Mreg_UKR cell product	60 weeks
Primary	biopsy-confirmed acute rejection incidence		60 weeks
Secondary	time to first acute rejection episode		60 weeks
Secondary	severity of acute rejection episodes	based on response to treatment and histological scoring	60 weeks
Secondary	total immunosuppressive burden	assessed at last study visit	60 weeks
Secondary	incidence of patients treated for subclinical acute rejection		60 weeks
Secondary	prevention of chronic graft dysfunction (chronic rejection or IF/TA)	assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures	60 weeks
Secondary	incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection		60 weeks
Secondary	avoidance of drug-related complications by immunosuppressant reduction	assessed by the incidence of reported adverse drug reactions	60 weeks
Secondary	incidence of embolic pulmonary complications and other embolic events		60 weeks
Secondary	incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure		1 week
Secondary	biochemical disturbances caused by cell infusion		1 week
Secondary	over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus		60 weeks
Secondary	over-suppression of the immune system assessed by the incidence of neoplasia		60 weeks
Secondary	immunological condition of study patients	an extensive immune monitoring program has been established in The ONE Study	60 weeks

External Links

•   ONE Study