Immunosuppressive Treatment of Living-donor Renal TransplantationPhase 1/2ONEnTreg13NCT02371434

The ONE Study nTreg Trial (ONEnTreg13)

A Phase 1/2 study testing autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs) in people with Immunosuppressive Treatment of Living-donor Renal Transplantation, run by Prof. Dr. Petra Reinke at 1 site in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Immunosuppressive Treatment of Living-donor Renal Transplantation
What is being tested?: autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 17 participants
Where: 1 siteGermany
Study dates: Feb 2015to 1 Nov 2017
Phase: Phase 1/2
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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).

Show all 23Show fewer

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.

Trial locations and contacts

1 site in 1 country.

Germany1 site

Charité University Medicine, Dept. of Nephrology and Internal Intensive Care
Berlin, 13353

Other trials in Germany

About this study

Official title: The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - nTregs Trial

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.

Read the detailed description

The ONE Study aims to explore the feasibility, safety and efficacy of regulatory cell therapies as adjunct immunosuppressive treatments in the context of living-donor renal transplantation.The clinical trial presented here (ONEnTreg13) will test autologous, polyclonally expanded CD4+CD25+FoxP3+ nTregs as a somatic cell-based medicinal product.

The objective of this study is to determine whether administration of nTregs to recipients of living-donor kidney transplants is safe and able to polarize the immunological response of the recipient away from graft rejection and towards graft acceptance, allowing a reduction in the doses of pharmacological maintenance immunosuppression.

Conditions: Immunosuppressive Treatment of Living-donor Renal Transplantation
Being tested: autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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.

Study groups in NCT02371434
Study group	Role	What they receive
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 Receives: Biological: autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)

What is being measured

The primary outcome is the main question the study is designed to answer.

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

Secondary outcomes (5)

Prevention of acute rejection will be secondarily assessed by measuring
1. 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.
Measured: 60 weeks
Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings
Measured: 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.
Measured: 60 weeks
Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).
Measured: 60 weeks
Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
Measured: 60 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Feb 20151 Nov 2017

First posted25 Feb 2015 (estimated)
Study startFeb 2015
Primary completion1 Nov 2017
Study completion1 Nov 2017

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (2)Papers the sponsor has linked to this study.
Other trials for Immunosuppressive Treatment of Living-donor Renal TransplantationStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1/2
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02371434
Sponsor's protocol ID: ONEnTreg13
Acronym: ONEnTreg13
Status last verified: Feb 2020
First submitted: 18 Feb 2015
Last updated: 5 Feb 2020
Results posted: No
Data monitoring committee: Yes

Publications

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.
PubMed 33087345
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.
PubMed 32446407

Study at a glance

From the registry record, last updated by the sponsor on 5 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - nTregs Trial
ClinicalTrials.gov ID: NCT02371434
Acronym / sponsor ID: ONEnTreg13 / ONEnTreg13
Conditions: Immunosuppressive Treatment of Living-donor Renal Transplantation
Phase: Phase 1/2
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Prof. Dr. Petra ReinkeUniversity, hospital or other
Study start: Feb 2015
Primary completion: 1 Nov 2017 (actual)
Study completion: 1 Nov 2017 (actual)
First posted: 25 Feb 2015 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
Treatment arm	Experimental	Biological: autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)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

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (3 listed)

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.

Key exclusion criteria (23 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
autologous CD4+CD25+FoxP3+ natural regulat. T cells (nTregs)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.	Biological	Treatment arm

Primary outcome

Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation
Time frame: 60 weeks
Incidence of infectious complications associated with cell administration.
Time frame: 60 weeks
Incidence of embolic pulmonary complications and other embolic events.
Time frame: 60 weeks
Incidence of immune responses resulting in anaphylactic reactions, cardiovascular compromise or other acute organ failure.
Time frame: 60 weeks
Biochemical disturbances associated with the cell infusion.
Time frame: 60 weeks
Over-suppression of the immune system assessed by the incidence of 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

5 secondary outcomes

Prevention of acute rejection will be secondarily assessed by measuring
Time frame: 60 weeks
Incidence of patients treated for subclinical acute rejection on the basis of histopathological findings
Time frame: 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.
Time frame: 60 weeks
Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).
Time frame: 60 weeks
Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
Time frame: 60 weeks

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2020.
Derived from this study: PubMed 33087345Roemhild 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.
Derived from this study: PubMed 32446407Sawitzki 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.

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation (time frame: 60 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02371434, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Feb 2020.