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The ONE Study UK Treg Trial (ONETreg1)

Primary Purpose

End-stage Renal Failure

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
Autologous regulatory T Cell Product
Sponsored by
Guy's and St Thomas' NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for End-stage Renal Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Recipient Inclusion Criteria

  1. Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor
  2. Aged at least 18 years
  3. Able to commence the immunosuppressive regimen at the protocol-specified time point
  4. Willing and able to participate in The ONE Study IM and HEC subprojects
  5. Signed and dated written informed consent

Exclusion Criteria

  1. Patient has previously received any tissue or organ transplant
  2. Known contraindication to the protocol-specified treatments / medications
  3. Genetically identical to the prospective organ donor at the HLA loci (0-0-0 mismatch)
  4. PRA grade > 40% within 6 months prior to enrolment
  5. Previous treatment with any desensitisation procedure (with or without IVIg)
  6. Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin)
  7. Evidence of significant local or systemic infection
  8. EBV-negative; serologically positive for anti-HIV-1,2; HBsAg; Anti-HBc; Anti-HCV-ab; Anti-HTLV-1,2 or syphilis (Treponema palladium)
  9. Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN (Upper Limit of Normal range)
  10. Malignant or pre-malignant haematological conditions
  11. Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives
  12. Any condition which, in the judgement of the Investigator, would place the subject at undue risk
  13. Ongoing treatment with systemic immunosuppressive drugs at study entry
  14. Participation in another clinical trial during the study or within 28 days prior to planned study entry
  15. Female patients of child-bearing potential with a positive pregnancy test at enrolment
  16. Female patients who are breast-feeding

  17. All female patients of child-bearing potential UNLESS:

    1. The patient is willing to maintain a highly effective method of birth control for the duration of the study
    2. The career, lifestyle, or sexual orientation of the patient ensures that there is no risk of pregnancy for the duration of the study (at the discretion of the Investigator)
  18. Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule
  19. 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
  20. Patients unable to freely give their informed consent (e.g. individuals under legal guardianship).

Donor Inclusion Criteria

  1. Eligible for live kidney donation
  2. Aged at least 18 years
  3. An ABO blood type compatible with the organ recipient
  4. Willing and able to provide a blood sample for The ONE Study IM Subproject
  5. Willing to provide personal and medical/biological data for the trial analysis
  6. Signed and dated written informed consent. Exclusion Criteria

1. Genetically identical to the prospective organ recipient at the HLA loci (0-0-0 mismatch) 2. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation 3. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator designated study personnel 4. Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship)

Sites / Locations

  • Guy's Hospital
  • The Oxford Transplant Centre - Churchill Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Autologous regulatory T Cell Product

Arm Description

Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed below: Prednisolone Day 0: 500 mg IV (250mg pre-op, 250mg intra-op) Day 1: 125 mg IV Day 2 to 14: 20.0 mg/day oral Week 3 to 4: 15.0 mg/day oral Week 5 to 8: 10.0 mg/day oral Week 9 to 12: 5.0 mg/day oral Week 13 to 14: 2.5 mg/day oral Week 15 to End: Cessation Mycophenolate Mofetil (MMF) Day -7 to -2: 500 mg/day oral Day -1 to 14: 2000 mg/day oral Week 3 to 36: 1000 mg/day oral Week 37 to 40: 750 mg/day oral Week 41 to 44: 500 mg/day oral Week 45 to 48: 250 mg/day oral Week 49 to End: Cessation Tacrolimus Day -4 to 14: 3-12 ng/ml oral Week 3 to 12: 3-10 ng/ml oral Week 13 to 36: 3-8 ng/ml oral Week 37 to End: 3-6 ng/ml oral

Outcomes

Primary Outcome Measures

Incidence of biopsy-confirmed acute rejection.

Secondary Outcome Measures

Time to first acute rejection episode
Severity of acute rejection episodes
Total immunosuppressive burden
Incidence of chronic graft dysfunction
Incidence of graft loss through rejection
Incidence of adverse drug reactions
Incidence of major and/or opportunistic infections
Incidence of neoplasia.

Full Information

First Posted
May 1, 2014
Last Updated
January 24, 2019
Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London
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1. Study Identification

Unique Protocol Identification Number
NCT02129881
Brief Title
The ONE Study UK Treg Trial
Acronym
ONETreg1
Official Title
The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation
Study Type
Interventional

2. Study Status

Record Verification Date
January 2019
Overall Recruitment Status
Completed
Study Start Date
April 2014 (Actual)
Primary Completion Date
March 23, 2017 (Actual)
Study Completion Date
March 23, 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Guy's and St Thomas' NHS Foundation Trust
Collaborators
King's College London

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
A study to assess cell therapy as a treatment to prevent kidney transplant rejection. The trial will involve purification of naturally occurring regulatory T cells (nTregs) from living-donor renal transplant recipients. The cells will then be grown in the laboratory and re-infused into the patient five days after the kidney transplant. This trial is part 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 nTreg therapy can eventually be used to recude the need for conventional immunosuppression in transplant recipients.
Detailed Description
Decades of immunosuppressive drug development has produced an array of powerful pharmacological agents, but the various drawbacks 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 Treg treatment, or other immunoregulatory cell-based therapies, can be advanced in the clinical management of solid organ transplant recipients. This particular Treg trial aims to explored the potential of Treg 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 seperate trials.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
End-stage Renal Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Autologous regulatory T Cell Product
Arm Type
Experimental
Arm Description
Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed below: Prednisolone Day 0: 500 mg IV (250mg pre-op, 250mg intra-op) Day 1: 125 mg IV Day 2 to 14: 20.0 mg/day oral Week 3 to 4: 15.0 mg/day oral Week 5 to 8: 10.0 mg/day oral Week 9 to 12: 5.0 mg/day oral Week 13 to 14: 2.5 mg/day oral Week 15 to End: Cessation Mycophenolate Mofetil (MMF) Day -7 to -2: 500 mg/day oral Day -1 to 14: 2000 mg/day oral Week 3 to 36: 1000 mg/day oral Week 37 to 40: 750 mg/day oral Week 41 to 44: 500 mg/day oral Week 45 to 48: 250 mg/day oral Week 49 to End: Cessation Tacrolimus Day -4 to 14: 3-12 ng/ml oral Week 3 to 12: 3-10 ng/ml oral Week 13 to 36: 3-8 ng/ml oral Week 37 to End: 3-6 ng/ml oral
Intervention Type
Biological
Intervention Name(s)
Autologous regulatory T Cell Product
Intervention Description
Autologous regulatory T Cell Product (1-10 million cells/kg) infused intravenously 5 days post renal transplantation. Recipients also receive prednisolone, mycophenolate mofetil, and tacrolimus as detailed in the arm description.
Primary Outcome Measure Information:
Title
Incidence of biopsy-confirmed acute rejection.
Time Frame
60 weeks
Secondary Outcome Measure Information:
Title
Time to first acute rejection episode
Time Frame
60 weeks
Title
Severity of acute rejection episodes
Time Frame
60 weeks
Title
Total immunosuppressive burden
Time Frame
60 weeks
Title
Incidence of chronic graft dysfunction
Time Frame
60 weeks
Title
Incidence of graft loss through rejection
Time Frame
60 weeks
Title
Incidence of adverse drug reactions
Time Frame
60 weeks
Title
Incidence of major and/or opportunistic infections
Time Frame
60 weeks
Title
Incidence of neoplasia.
Time Frame
60 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Recipient Inclusion Criteria Chronic renal insufficiency necessitating kidney transplantation and approved to receive a primary kidney allograft from a living donor Aged at least 18 years Able to commence the immunosuppressive regimen at the protocol-specified time point Willing and able to participate in The ONE Study IM and HEC subprojects Signed and dated written informed consent Exclusion Criteria Patient has previously received any tissue or organ transplant Known contraindication to the protocol-specified treatments / medications Genetically identical to the prospective organ donor at the HLA loci (0-0-0 mismatch) PRA grade > 40% within 6 months prior to enrolment Previous treatment with any desensitisation procedure (with or without IVIg) Concomitant malignancy or history of malignancy within 5 years prior to planned study entry (excluding successfully-treated non-metastatic basal/squamous cell carcinoma of the skin) Evidence of significant local or systemic infection EBV-negative; serologically positive for anti-HIV-1,2; HBsAg; Anti-HBc; Anti-HCV-ab; Anti-HTLV-1,2 or syphilis (Treponema palladium) Significant liver disease, defined as persistently elevated AST and/or ALT levels > 2 x ULN (Upper Limit of Normal range) Malignant or pre-malignant haematological conditions Any uncontrolled medical condition or concurrent disease that could interfere with the study objectives Any condition which, in the judgement of 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 child-bearing potential with a positive pregnancy test at enrolment Female patients who are breast-feeding All female patients of child-bearing potential UNLESS: The patient is willing to maintain a highly effective method of birth control for the duration of the study The career, lifestyle, or sexual orientation of the patient ensures that there is no risk of pregnancy for the duration of the study (at the discretion of the Investigator) Psychological, familial, sociological or geographical factors potentially hampering compliance with the study protocol and follow-up visit schedule 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 Patients unable to freely give their informed consent (e.g. individuals under legal guardianship). Donor Inclusion Criteria Eligible for live kidney donation Aged at least 18 years An ABO blood type compatible with the organ recipient Willing and able to provide a blood sample for The ONE Study IM Subproject Willing to provide personal and medical/biological data for the trial analysis Signed and dated written informed consent. Exclusion Criteria 1. Genetically identical to the prospective organ recipient at the HLA loci (0-0-0 mismatch) 2. Exposure to any investigational agents at the time of kidney donation, or within 28 days prior to kidney donation 3. Any form of substance abuse, psychiatric disorder, or other condition that, in the opinion of the Investigator, may invalidate communication with the Investigator designated study personnel 4. Subjects unable to freely give their informed consent (e.g. individuals under legal guardianship)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Giovanna Lombardi, PhD
Organizational Affiliation
King's College Hospital NHS Trust
Official's Role
Study Director
Facility Information:
Facility Name
Guy's Hospital
City
London
ZIP/Postal Code
SE1 9RT
Country
United Kingdom
Facility Name
The Oxford Transplant Centre - Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
32446407
Citation
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. Erratum In: Lancet. 2020 Jun 27;395(10242):1972.
Results Reference
derived
Links:
URL
http://www.onestudy.org
Description
One Study

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The ONE Study UK Treg Trial

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