- ICH GCP
- Registro de ensayos clínicos de EE. UU.
- Ensayo clínico NCT07917923
A Clinical Study to Evaluate the Safety and Efficacy of GT802 Injection in the Treatment of Refractory Generalized Myasthenia Gravis
This is a single-arm, open-label, dose-escalating clinical trial designed to evaluate the safety, efficacy and cellular pharmacokinetics of GT802 in the treatment of refractory generalized myasthenia gravis.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
The study includes 3 planned dose cohorts as follows: Dose 1: total of 8.5 mg, administered as 4 infusions at 1.0 mg, 1.5 mg, 3.0 mg, and 3.0 mg; Dose 2: total of 13.5 mg, administered as 4 infusions at 1.5 mg, 3.0 mg, 4.5 mg, and 4.5 mg; De-escalation dose: total of 4.5 mg, administered as 4 infusions at 0.5 mg, 1.0 mg, 1.5 mg, and 1.5 mg.
Each participant will receive treatment from one dose cohort. It is planned to enroll 4-12 participants in total, with the number of participants per dose cohort as follows: Dose 1: 1-6 participants; Dose 2: 3-6 participants; De-escalation dose: 0-6 participants.
Tipo de estudio
Inscripción (Estimado)
Fase
- Fase temprana 1
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Yuhang Cheng
- Número de teléfono: +86 13125197960
- Correo electrónico: chengyh_tj@163.com
Ubicaciones de estudio
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Hubei
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Wuhan, Hubei, Porcelana, 430000
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Investigador principal:
- Daishi Tian
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Investigador principal:
- Chuan Qin
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Contacto:
- Daishi Tian
- Número de teléfono: +86 13607178809
- Correo electrónico: tiands@tjh.tjmu.edu.cn
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
Acepta Voluntarios Saludables
Géneros elegibles para el estudio
Descripción
Inclusion Criteria:
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1. The participant or their legally authorized representative voluntarily signs the written informed consent form and is willing and able to comply with the study procedures.
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2. Aged 18-65 years (inclusive) at the time of informed consent, without gender restriction.
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3. Expected survival > 12 weeks.
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4. Any prior systemic therapy for the indication must have a washout period of at least 4 weeks or 5 half-lives, whichever is shorter, before the participant is scheduled to receive study treatment.
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5. Toxicities attributable to prior treatment must have stabilized and recovered to Grade ≤1.
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6. Refractory generalized myasthenia gravis, as defined in the protocol.
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7. Screening laboratory results meet the criteria specified in the protocol.
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8. Pregnancy requirements:
- At screening, serum beta human chorionic gonadotropin (β-hCG) pregnancy test is negative as confirmed by the investigator.
- Agrees to refrain from breastfeeding during study participation until at least 1 year after infusion of GT802 Injection or until GT802 cells are no longer detectable by 2 consecutive flow cytometry assays, whichever occurs later.
- Male participants with female partners and female participants of childbearing potential agree to use highly effective contraception (e.g., oral contraceptives, intrauterine device or condoms) starting at screening and continuing until at least 1 year after infusion of GT802 Injection or until GT802 cells are no longer detectable by 2 consecutive flow cytometry assays, whichever occurs later. Male participants must agree to use condoms during sexual contact with pregnant females or females of childbearing potential for at least 1 year after GT802 Injection infusion, even after successful vasectomy.
Exclusion Criteria:
- 1. Contraindication or hypersensitivity to any component of the investigational product.
- 2. Presence of conditions specified in the protocol within 6 months prior to signing the informed consent form.[沈9.1]
- 3. History of active malignancy or any malignancy within 5 years prior to screening.
- 4. Presence of any active or untreated thymoma, or history of thymic carcinoma or other early pseudotumors of thymic malignancy.
- 5. Autoimmune diseases other than the study disease that require systemic glucocorticoids or immunosuppressants.
- 6. Requirement for long-term administration of medications affecting coagulation function.
- 7. Participants with clinically obvious bleeding symptoms or definite bleeding tendency within 6 months before screening.
- 8. Presence of severe underlying medical conditions at screening.
- 9. Positive result for any of the following tests: a) Positive human immunodeficiency virus (HIV) antibody; b) Positive hepatitis B surface antigen (HBsAg) and/or positive hepatitis B core antibody (HBcAb), with HBV-DNA above the lower limit of quantitation of the assay; c) Positive hepatitis C virus (HCV) antibody, with HCV-RNA above the lower limit of quantitation of the assay; d) Positive syphilis antibody (excluding false-positive results caused by underlying diseases).
- 10. Positive cytomegalovirus (CMV)-DNA and Epstein Barr virus (EBV)-DNA in peripheral blood.
- 11. Active tuberculosis prior to screening.
- 12. Received any other investigational medicinal product within 4 weeks before signing the informed consent form (ICF).
- 13. Received intravenous immunoglobulin, plasma exchange or immunoadsorption therapy within 4 weeks prior to study treatment.
- 14. Received B-cell targeted therapy within 1 month prior to study treatment.
- 15. Received tacrolimus, cyclosporine, azathioprine, mycophenolate mofetil, mycophenolic acid, methotrexate, etc., within 2 weeks prior to study treatment.
- 16. Received neonatal Fc receptor (FcRn) antagonist therapy within 2 weeks prior to study treatment.
- 17. Received complement inhibition therapy within 2 weeks prior to study treatment.
- 18. Received systemic glucocorticoids at a dose >10 mg/day prednisone equivalent within 7 days prior to study treatment.
- 19. Received live attenuated vaccines or mRNA vaccines within 8 weeks before enrollment, or inactivated vaccines within 4 weeks before enrollment.
- 20. Underwent major surgery within 8 weeks before screening, or planned to undergo surgery during the study period.
- 21. History of organ transplantation, splenectomy, allogeneic or autologous stem cell transplantation.
- 22. Presence of non-removable, clinically significant long-term indwelling catheters or drainage devices.
- 23. Uncontrolled large-volume serous cavity effusion despite treatment.
- 24. Prior receipt of CAR-T products targeting any antigen or other gene-edited cell biotherapies.
- 25. The investigator judges that any condition exists that would prevent the participant from completing the entire trial, confound the trial results, or make trial participation not in the participant's best interest.
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 |
|---|---|
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Experimental: GT802 Injection treatment group
Participants with MG administered GT802 Injection |
Injection |
¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Adverse Events (AEs) occurring after infusion and their proportions
Periodo de tiempo: From infusion to at least 1 year
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Adverse Events (AEs) occurring after infusion and their proportions |
From infusion to at least 1 year
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
|
Quantitative Myasthenia Gravis (QMG) score
Periodo de tiempo: From infusion to 12 months
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To assess the preliminary efficacy of GT802 Injection in participants with refractory generalized myasthenia gravis per QMG score. |
From infusion to 12 months
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Myasthenia Gravis Activities of Daily Living (MG-ADL) score
Periodo de tiempo: From infusion to 12 months
|
To assess the preliminary efficacy of GT802 Injection in participants with refractory generalized myasthenia gravis per MG-ADL score. |
From infusion to 12 months
|
|
Time to maximum amplification (Tmax)
Periodo de tiempo: From infusion to 12 months
|
Time to maximum amplification (Tmax) of cells following GT802 infusion |
From infusion to 12 months
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Maximum amplification (Cmax)
Periodo de tiempo: From infusion to 12 months
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The maximum observed concentration of the circulating GT802 CAR-T cells |
From infusion to 12 months
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Area under the curve (AUC)
Periodo de tiempo: From infusion to 12 months
|
Area under the curve (AUC) of cellular expansion following GT802 infusion |
From infusion to 12 months
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Duration of Detectable Concentration (Tlast)
Periodo de tiempo: From infusion to 12 months
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Duration of Detectable Concentration (Tlast) refers to the time period from the infusion of GT802 cells to the last time point at which the target cells can be detected in the peripheral blood or target tissues. |
From infusion to 12 months
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Chimeric Antigen Receptor T cell (CAR-T)-associated serum cytokines
Periodo de tiempo: From infusion to 2 months
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Monitor serum cytokine levels after infusion |
From infusion to 2 months
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Anti-drug antibodies (ADA) Response to GT802 Measured by Immunoassay.
Periodo de tiempo: From infusion to 12 months
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Changes in anti-drug antibodies (ADA) before and after treatment. Serum anti-drug antibody (ADA) response to GT802, including anti-CAR and anti-PEG antibodies, measured by immunoassay. Samples collected at pre-screening (PEG only), Day 14, Day 28, Month 3, Month 6, and Month 12 post-first infusion. Positive results trigger titer confirmation and continued monitoring until negative or below lower limit of detection. |
From infusion to 12 months
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Colaboradores e Investigadores
Patrocinador
Colaboradores
Investigadores
- Investigador principal: Chuan Qin, Tongji Hospital
- Investigador principal: Daishi Tian, Tongji Hospital
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
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
Términos MeSH relevantes adicionales
- Enfermedades del Sistema Nervioso
- Neoplasias por sitio
- Neoplasias
- Enfermedades Neuromusculares
- Enfermedades autoinmunes
- Enfermedades del sistema inmunológico
- Enfermedades Autoinmunes del Sistema Nervioso
- Enfermedades neurodegenerativas
- Síndromes Paraneoplásicos Del Sistema Nervioso
- Neoplasias del Sistema Nervioso
- Síndromes paraneoplásicos
- Enfermedades de la unión neuromuscular
- Miastenia gravis
Otros números de identificación del estudio
- GRIT-CD-CHN-802-003
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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