The ONE Study nTreg Trial (ONEnTreg13)

NCT02371434 | Completed Phase 1 DMC

• 1 other identifier: ONEnTreg13
• Study Type: interventional
• Target: 17
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this trial is to collect evidence of the safety of administering autologous CD4+CD25+FoxP3+ natural regulatory T cells (nTregs) to living-donor renal transplant recipients. In addition, the study will determine whether post-transplant nTregs infusion allows a tapering of conventional maintenance immunosuppression within 60 weeks after transplantation.

Conditions

Immunosuppressive Treatment of Living-donor Renal Transplantation

Outcome Measures

Primary Outcomes (7)

• 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 (5)

• Prevention of acute rejection will be secondarily assessed by measuring

  60 weeks

• Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings

  60 weeks

• Prevention of chronic graft dysfunction (chronic rejection or IF/TA) will be assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.

  60 weeks

• Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).

  60 weeks

• Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.

  60 weeks

Study Arms (1)

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

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.

Treatment arm

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Prof. Dr. Petra Reinke: lead

Study Sites (1)

Charité University Medicine, Dept. of Nephrology and Internal Intensive Care

Berlin, 13353, Germany

Location

Related Publications (2)

• 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.

  PMID: 33087345 DERIVED

• Sawitzki B, Harden PN, Reinke P, Moreau A, Hutchinson JA, Game DS, Tang Q, Guinan EC, Battaglia M, Burlingham WJ, Roberts ISD, Streitz M, Josien R, Boger CA, Scotta C, Markmann JF, Hester JL, Juerchott K, Braudeau C, James B, Contreras-Ruiz L, van der Net JB, Bergler T, Caldara R, Petchey W, Edinger M, Dupas N, Kapinsky M, Mutzbauer I, Otto NM, Ollinger R, Hernandez-Fuentes MP, Issa F, Ahrens N, Meyenberg C, Karitzky S, Kunzendorf U, Knechtle SJ, Grinyo J, Morris PJ, Brent L, Bushell A, Turka LA, Bluestone JA, Lechler RI, Schlitt HJ, Cuturi MC, Schlickeiser S, Friend PJ, Miloud T, Scheffold A, Secchi A, Crisalli K, Kang SM, Hilton R, Banas B, Blancho G, Volk HD, Lombardi G, Wood KJ, Geissler EK. Regulatory cell therapy in kidney transplantation (The ONE Study): a harmonised design and analysis of seven non-randomised, single-arm, phase 1/2A trials. Lancet. 2020 May 23;395(10237):1627-1639. doi: 10.1016/S0140-6736(20)30167-7.

  PMID: 32446407 DERIVED

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Nephrology

Study Record Dates

• First Submitted: February 18, 2015
• First Posted: February 25, 2015
• Study Start: February 1, 2015
• Primary Completion: November 1, 2017
• Study Completion: November 1, 2017
• Last Updated: February 5, 2020

Record last verified: 2020-02

Locations

DE (1)