- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT02371434
The ONE Study nTreg Trial (ONEnTreg13) (ONEnTreg13)
The ONE Study: A Unified Approach to Evaluating Cellular Immunotherapy in Solid Organ Transplantation - nTregs Trial
Descripción general del estudio
Estado
Intervención / Tratamiento
Descripción detallada
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.
Tipo de estudio
Inscripción (Actual)
Fase
- Fase 2
- Fase 1
Contactos y Ubicaciones
Ubicaciones de estudio
-
-
-
Berlin, Alemania, 13353
- Charité University Medicine, Dept. of Nephrology and Internal Intensive Care
-
-
Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
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.
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: N / A
- Modelo Intervencionista: Asignación de un solo grupo
- Enmascaramiento: Ninguno (etiqueta abierta)
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
|---|---|
|
Experimental: Treatment arm
Patients in ONEnTreg13 will be treated with four immunosuppressive agents, all of which are classified as an Investigational Medicinal Products (IMPs):
|
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.
|
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Periodo de tiempo |
|---|---|
|
Incidence of biopsy-confirmed acute rejection (BCAR) within 60 weeks of organ transplantation
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Incidence of infectious complications associated with cell administration.
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Incidence of embolic pulmonary complications and other embolic events.
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Incidence of immune responses resulting in anaphylactic reactions, cardiovascular compromise or other acute organ failure.
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Biochemical disturbances associated with the cell infusion.
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Over-suppression of the immune system assessed by the incidence of opportunistic infections, especially, CMV, EBV and polyoma virus.
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
Over-suppression of the immune system assessed by the incidence of neoplasia.
Periodo de tiempo: 60 weeks
|
60 weeks
|
Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Incidencia de pacientes tratados por rechazo agudo subclínico según los hallazgos histopatológicos
Periodo de tiempo: 60 semanas
|
60 semanas
|
|
|
Prevention of acute rejection will be secondarily assessed by measuring
Periodo de tiempo: 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.
Periodo de tiempo: 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).
Periodo de tiempo: 60 weeks
|
60 weeks
|
|
|
Avoidance of drug-related complications by immunosuppressant reduction will be assessed by the incidence of reported adverse drug reactions.
Periodo de tiempo: 60 weeks
|
60 weeks
|
Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- 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.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio
Finalización primaria (Actual)
Finalización del estudio (Actual)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Estimar)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Otros números de identificación del estudio
- ONEnTreg13
Esta información se obtuvo directamente del sitio web clinicaltrials.gov sin cambios. Si tiene alguna solicitud para cambiar, eliminar o actualizar los detalles de su estudio, comuníquese con register@clinicaltrials.gov. Tan pronto como se implemente un cambio en clinicaltrials.gov, también se actualizará automáticamente en nuestro sitio web. .