- ICH GCP
- Yhdysvaltain kliinisten tutkimusten rekisteri
- Kliininen tutkimus NCT02371434
The ONE Study nTreg Trial (ONEnTreg13) (ONEnTreg13)
The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - nTregs Trial
Tutkimuksen yleiskatsaus
Tila
Interventio / Hoito
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Ilmoittautuminen (Todellinen)
Vaihe
- Vaihe 2
- Vaihe 1
Yhteystiedot ja paikat
Opiskelupaikat
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Berlin, Saksa, 13353
- Charité University Medicine, Dept. of Nephrology and Internal Intensive Care
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Osallistumiskriteerit
Kelpoisuusvaatimukset
Opintokelpoiset iät
Hyväksyy terveitä vapaaehtoisia
Sukupuolet, jotka voivat opiskella
Kuvaus
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.
Opintosuunnitelma
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
- Ensisijainen käyttötarkoitus: Hoito
- Jako: Ei käytössä
- Inventiomalli: Yksittäinen ryhmätehtävä
- Naamiointi: Ei mitään (avoin tarra)
Aseet ja interventiot
Osallistujaryhmä / Arm |
Interventio / Hoito |
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Kokeellinen: Treatment arm
Patients in ONEnTreg13 will be treated with four immunosuppressive agents, all of which are classified as an Investigational Medicinal Products (IMPs):
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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.
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Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Aikaikkuna |
|---|---|
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Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation
Aikaikkuna: 60 weeks
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60 weeks
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Incidence of infectious complications associated with cell administration.
Aikaikkuna: 60 weeks
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60 weeks
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Incidence of embolic pulmonary complications and other embolic events.
Aikaikkuna: 60 weeks
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60 weeks
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Incidence of immune responses resulting in anaphylactic reactions, cardiovascular compromise or other acute organ failure.
Aikaikkuna: 60 weeks
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60 weeks
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Biochemical disturbances associated with the cell infusion.
Aikaikkuna: 60 weeks
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60 weeks
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Over-suppression of the immune system assessed by the incidence of opportunistic infections, especially, CMV, EBV and polyoma virus.
Aikaikkuna: 60 weeks
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60 weeks
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Over-suppression of the immune system assessed by the incidence of neoplasia.
Aikaikkuna: 60 weeks
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60 weeks
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Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
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Subkliinisen akuutin hyljinnän vuoksi hoidettujen potilaiden ilmaantuvuus histopatologisten löydösten perusteella
Aikaikkuna: 60 viikkoa
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60 viikkoa
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Prevention of acute rejection will be secondarily assessed by measuring
Aikaikkuna: 60 weeks
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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.
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60 weeks
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Prevention of chronic graft dysfunction (chronic rejection or IF/TA) will be assessed by clinical (impairment of GFR) and histopathological (Banff staging) measures.
Aikaikkuna: 60 weeks
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60 weeks
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Incidence of post-transplant dialysis, inclusion on the transplant waiting list or retransplantation following graft loss through rejection (acute or chronic).
Aikaikkuna: 60 weeks
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60 weeks
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Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
Aikaikkuna: 60 weeks
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60 weeks
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Yhteistyökumppanit ja tutkijat
Sponsori
Julkaisuja ja hyödyllisiä linkkejä
Yleiset julkaisut
- 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.
- 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.
Opintojen ennätyspäivät
Opi tärkeimmät päivämäärät
Opiskelun aloitus
Ensisijainen valmistuminen (Todellinen)
Opintojen valmistuminen (Todellinen)
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Ensimmäinen Lähetetty (Arvio)
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Viimeksi vahvistettu
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Muut tutkimustunnusnumerot
- ONEnTreg13
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