The ONE Study nTreg Trial (ONEnTreg13) | NCT02371434

NCT02371434

Protocol Section

Identification Module

Results Section

No data available

No data is available for this block.

Annotation Section

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No data is available for this block.

Document Section

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No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Treatment arm	Experimental	Patients in ONEnTreg13 will be treated with four immunosuppressive agents, all of which are classified as an Investigational Medicinal Products (IMPs): nTregs Prednisolone MMF Tacrolimus	Biological: autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)	Biological	autologous CD4+CD25+FoxP3+ natural regulatory T cells (nTregs). nTregs will be infused at escalating doses of 0.5 x 10^6, 1 x 10^6, and 2.5-3 x 10^6 cells/kg body weight in cohorts of three patients each.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation		60 weeks
Incidence of infectious complications associated with cell administration.		60 weeks
Incidence of embolic pulmonary complications and other embolic events.		60 weeks
Incidence of immune responses resulting in anaphylactic reactions, cardiovascular compromise or other acute organ failure.		60 weeks
Biochemical disturbances associated with the cell infusion.		60 weeks
Over-suppression of the immune system assessed by the incidence of opportunistic infections, especially, CMV, EBV and polyoma virus.		60 weeks
Over-suppression of the immune system assessed by the incidence of neoplasia.		60 weeks

Secondary Outcomes

Measure	Description	Time Frame
Prevention of acute rejection will be secondarily assessed by measuring	i) time to first acute rejection episode ii) severity of acute rejection episodes based on response to treatment and histological scoring iii) the level of total immunosuppression drugs at the final trial visit.	60 weeks
Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings

Eligibility Module

Eligibility Criteria

Inclusion Criteria for organ recipients:

Chronic renal insufficiency with a GFR < 15 ml/min, accepted by the organ transplantation conference, registered by ET (Euro Transplant) and having a positive vote from the living donor ethic commission (Lebendspendekommission) at the Berlin Medical Association.
Willing and able to participate in The ONE Study IM and HEC Subprojects.
Signed and dated written informed consent. For patients unable to read and/or write, oral informed consent observed by an independent witness is acceptable if the patient has fully understood oral information given by the Investigator. The witness should sign the consent form on behalf of the patient.

Exclusion Criteria for organ recipients:

Patient has previously received any tissue or organ transplant other than the planned kidney graft.
Known contraindication to protocol-specified treatments / medications.
Genetically identical to the prospective organ donor at the HLA loci, the so called "full house match" (0-0-0 mismatch).
Panel-Reactive Antibody (PRA) grade > 40% within last 6 months before transplantation.
Previous treatment with any desensitization procedure (with or without IVIg).
Concomitant malignancy or history of malignancy within 5 years before study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin).
Evidence of significant local or systemic infection.
CMV-negative recipient receiving a kidney from a CMV-positive donor. EBV-negative recipient receiving a kidney from an EBV-positive donor.
HIV-positive or suffering chronic viral hepatitis.
Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN.
Malignant or pre-malignant hematological conditions.
Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives.
Any condition which, according to the Investigator, would place the subject at undue risk.
Ongoing treatment with systemic immunosuppressive drugs at study entry.
Participation in another clinical trial during the study or within 28 days prior to planned study entry.
Female patients of childbearing potential with a positive pregnancy test at enrolment.
Female patients who are breast-feeding.
All female patients of childbearing potential unless the patient is willing to maintain a highly effective method of birth control for the duration of the study.
Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule.
Any form of drug or alcohol abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator and/or designated study personnel.
Patients unable to freely give their informed consent (e.g. patients under legal guardianship).
Patients who are committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
Known allergy/hypersensitivity to any component of the study product.

PubMed Identifier	Type	Citation	Retractions
33087345	Derived	Roemhild A, Otto NM, Moll G, Abou-El-Enein M, Kaiser D, Bold G, Schachtner T, Choi M, Oellinger R, Landwehr-Kenzel S, Juerchott K, Sawitzki B, Giesler C, Sefrin A, Beier C, Wagner DL, Schlickeiser S, Streitz M, Schmueck-Henneresse M, Amini L, Stervbo U, Babel N, Volk HD, Reinke P. Regulatory T cells for minimising immune suppression in kidney transplantation: phase I/IIa clinical trial. BMJ. 2020 Oct 21;371:m3734. doi: 10.1136/bmj.m3734.
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