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Renal Failure, End StagePhase 1/2ONEmreg12NCT02085629

The ONE Study M Reg Trial

A Phase 1/2 study testing Donor M reg (Mreg_UKR) in people with Renal Failure, End Stage, run by University of Regensburg at 1 site in Germany.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Renal Failure, End Stage
What is being tested?
Donor M reg (Mreg_UKR)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
8 participants
Where
1 siteGermany
Study dates
24 Jul 2014to 3 Dec 2018
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 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
  • Eligible for live kidney donation
Show all 11Show fewer
  • 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

Who cannot join

  • 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)
Show all 32Show fewer
  • 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
  • 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

Trial locations and contacts

1 site in 1 country.

Germany1 site

  • University Hospital Regensburg

    Regensburg, 93053

Other trials in Germany

About this study

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

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.

Read the detailed 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.

Being tested
Donor M reg (Mreg_UKR)
Keywords
renal failure, end stage, renal transplantation, cell therapy, macrophages, monocyte derived, immune tolerance, ONE Study, immunotherapy
Medical subject headings
Kidney Failure, Chronic

What participants receive

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

  • Donor M reg (Mreg_UKR)Biological

    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).

Study groups in NCT02085629
Study groupRoleWhat they receive
M reg treatmentExperimentalDonor M reg (2.5-7.5 million cells/kg) IV infused (6-7d before Tx) into recipients of a LD renal Tx. Recipients also receive prednisolone, mycophenolate mofetil and tacrolimus, as detailed below: Prednisolone * D 0: 500 mg IV * D 1: 125 mg IV * D 2 - 14: 20.0 mg/d (oral) * Wk 3 - 4: 15.0 mg/d * Wk 5 - 8: 10.0 mg/d * Wk 9 - 12: 5.0 mg/d * Wk 13 - 14: 2.5 mg/d * Wk 15 - End: Cessation MMF (or biologic equiv.) * D -7 to -2: 500 mg/d (250mg 2x/d) * D -1 to 14: 2000 mg/d * Wk 3 - 36: 1000 mg/d * Wk 37 - 40: 750 mg/d * Wk 41 - 44: 500 mg/d * Wk 45 - 48: 250 mg/d * Wk 49 - End: Cessation NOTE: MMF tapering will only happen if a 36-Wk biopsy shows no signs of subclinical rejection or if there is no evidence of declining renal function or if the clinician has any other concern about dose reduction. Tacrolimus (or biologic equiv.) * ≤ 48 h pre-Tx to D 14: 3-12 ng/ml * Wk 3 - 12: 3-10 ng/ml * Wk 13 - 36: 3-8 ng/ml * Wk 37 - End: 3-6 ng/ml
Receives: Biological: Donor M reg (Mreg_UKR)

What is being measured

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

  1. biopsy-confirmed acute rejection incidence

    Measured: 60 weeks

Secondary outcomes (13)

  1. time to first acute rejection episode

    Measured: 60 weeks

  2. severity of acute rejection episodes

    based on response to treatment and histological scoring

    Measured: 60 weeks

  3. total immunosuppressive burden

    assessed at last study visit

    Measured: 60 weeks

  4. incidence of patients treated for subclinical acute rejection

    Measured: 60 weeks

  5. prevention of chronic graft dysfunction (chronic rejection or IF/TA)

    assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures

    Measured: 60 weeks

  6. incidence of post-transplant dialysis, inclusion on the transplant waiting list or re-transplantation following graft loss through rejection

    Measured: 60 weeks

  7. avoidance of drug-related complications by immunosuppressant reduction

    assessed by the incidence of reported adverse drug reactions

    Measured: 60 weeks

  8. incidence of embolic pulmonary complications and other embolic events

    Measured: 60 weeks

  9. incidence of immunological reactions resulting in anaphylactoid reactions, immediate cardiovascular compromise or other acute organ failure

    Measured: 1 week

  10. biochemical disturbances caused by cell infusion

    Measured: 1 week

  11. over-suppression of the immune system assessed by the incidence of major and/or opportunistic infections, especially CMV, EBV and polyoma virus

    Measured: 60 weeks

  12. over-suppression of the immune system assessed by the incidence of neoplasia

    Measured: 60 weeks

  13. immunological condition of study patients

    an extensive immune monitoring program has been established in The ONE Study

    Measured: 60 weeks

Timeline

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

  1. First posted13 Mar 2014 (estimated)
  2. Study start24 Jul 2014
  3. Primary completion3 Dec 2018
  4. Study completion3 Dec 2018

Why it stopped: Insufficient rate of patient recruitment and treatment.

Resources

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
8 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02085629
Sponsor's protocol ID
ONEmreg12
Other IDs
2013-000999-15, grant number 260687
Acronym
ONEmreg12
Status last verified
Apr 2019
First submitted
10 Mar 2014
Last updated
18 Apr 2019
Results posted
No
Data monitoring committee
Yes

Publications

  • 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. No abstract available.

    PubMed 23369457

  • 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

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Donor M reg (Mreg_UKR) in people with Renal Failure, End Stage, run by University of Regensburg at 1 site in Germany.

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 11 inclusion and 32 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: stopped early, as of the sponsor's last update on 18 Apr 2019. 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 was stopped early (reason given: Insufficient rate of patient recruitment and treatment.). Results are not available in the source record.

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?

biopsy-confirmed acute rejection incidence (time frame: 60 weeks). 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 NCT02085629, 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 18 Apr 2019.

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