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The ONE Study nTreg Trial (ONEnTreg13) (ONEnTreg13)

3 februari 2020 uppdaterad av: Prof. Dr. Petra Reinke

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.

Studieöversikt

Detaljerad beskrivning

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.

Studietyp

Interventionell

Inskrivning (Faktisk)

17

Fas

  • Fas 2
  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

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

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 65 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

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.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Behandling
  • Tilldelning: N/A
  • Interventionsmodell: Enskild gruppuppgift
  • Maskning: Ingen (Open Label)

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Treatment arm

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
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.

Vad mäter studien?

Primära resultatmått

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

Sekundära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Incidensen av patienter som behandlas för subklinisk akut avstötning på basis av histopatologiska fynd
Tidsram: 60 veckor
60 veckor
Prevention of acute rejection will be secondarily assessed by measuring
Tidsram: 60 weeks
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
Prevention of chronic graft dysfunction (chronic rejection or IF/TA) will be assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.
Tidsram: 60 weeks
60 weeks
Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).
Tidsram: 60 weeks
60 weeks
Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
Tidsram: 60 weeks
60 weeks

Samarbetspartners och utredare

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Publikationer och användbara länkar

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Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart

1 februari 2015

Primärt slutförande (Faktisk)

1 november 2017

Avslutad studie (Faktisk)

1 november 2017

Studieregistreringsdatum

Först inskickad

18 februari 2015

Först inskickad som uppfyllde QC-kriterierna

19 februari 2015

Första postat (Uppskatta)

25 februari 2015

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

5 februari 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

3 februari 2020

Senast verifierad

1 februari 2020

Mer information

Termer relaterade till denna studie

Andra studie-ID-nummer

  • ONEnTreg13

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