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.
Przegląd badań
Status
Status
Warunki
Warunki
Interwencja / Leczenie
Interwencja / Leczenie
Szczegółowy opis
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.
Typ studiów
Typ studiów
Zapisy (Szacowany)
Zapisy
Faza
Faza
- Wczesna faza 1
Kontakty i lokalizacje
Kontakt w sprawie studiów
Kontakt w sprawie studiów
- Nazwa: Yuhang Cheng
- Numer telefonu: +86 13125197960
- E-mail: chengyh_tj@163.com
Lokalizacje studiów
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Hubei
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Wuhan, Hubei, Chiny, 430000
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Główny śledczy:
- Daishi Tian
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Główny śledczy:
- Chuan Qin
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Kontakt:
- Daishi Tian
- Numer telefonu: +86 13607178809
- E-mail: tiands@tjh.tjmu.edu.cn
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Kryteria uczestnictwa
Kryteria kwalifikacji
Kryteria kwalifikacji
Wiek uprawniający do nauki
Akceptuje zdrowych ochotników
Płeć kwalifikująca się do nauki
Opis
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 studiów
Jak projektuje się badanie?
Szczegóły projektu
- Główny cel: Leczenie
- Przydział: Nie dotyczy
- Model interwencyjny: Zadanie dla jednej grupy
- Maskowanie: Brak (otwarta etykieta)
Liczba ramion
Broń i interwencje
Grupa uczestników / ArmGrupa uczestników / Arm |
Interwencja / LeczenieInterwencja / Leczenie |
|---|---|
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Eksperymentalny: GT802 Injection treatment group
Participants with MG administered GT802 Injection |
Injection |
Co mierzy badanie?
Podstawowe miary wyniku
Podstawowe miary wyniku
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Adverse Events (AEs) occurring after infusion and their proportions
Ramy czasowe: From infusion to at least 1 year
|
Adverse Events (AEs) occurring after infusion and their proportions |
From infusion to at least 1 year
|
Miary wyników drugorzędnych
Miary wyników drugorzędnych
Miara wyniku |
Opis środka |
Ramy czasowe |
|---|---|---|
|
Quantitative Myasthenia Gravis (QMG) score
Ramy czasowe: From infusion to 12 months
|
To assess the preliminary efficacy of GT802 Injection in participants with refractory generalized myasthenia gravis per QMG score. |
From infusion to 12 months
|
|
Myasthenia Gravis Activities of Daily Living (MG-ADL) score
Ramy czasowe: 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)
Ramy czasowe: From infusion to 12 months
|
Time to maximum amplification (Tmax) of cells following GT802 infusion |
From infusion to 12 months
|
|
Maximum amplification (Cmax)
Ramy czasowe: From infusion to 12 months
|
The maximum observed concentration of the circulating GT802 CAR-T cells |
From infusion to 12 months
|
|
Area under the curve (AUC)
Ramy czasowe: 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)
Ramy czasowe: From infusion to 12 months
|
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
|
|
Chimeric Antigen Receptor T cell (CAR-T)-associated serum cytokines
Ramy czasowe: From infusion to 2 months
|
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.
Ramy czasowe: 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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Współpracownicy i badacze
Sponsor
Sponsor
Współpracownicy
Współpracownicy
Śledczy
Śledczy
- Główny śledczy: Chuan Qin, Tongji Hospital
- Główny śledczy: Daishi Tian, Tongji Hospital
Daty zapisu na studia
Główne daty studiów
Rozpoczęcie studiów (Szacowany)
Rozpoczęcie studiów
Zakończenie podstawowe (Szacowany)
Zakończenie podstawowe
Ukończenie studiów (Szacowany)
Ukończenie studiów
Daty rejestracji na studia
Pierwszy przesłany
Pierwszy przesłany
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy przesłany, który spełnia kryteria kontroli jakości
Pierwszy wysłany (Rzeczywisty)
Pierwszy wysłany
Aktualizacje rekordów badań
Ostatnia wysłana aktualizacja (Rzeczywisty)
Ostatnia wysłana aktualizacja
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia przesłana aktualizacja, która spełniała kryteria kontroli jakości
Ostatnia weryfikacja
Ostatnia weryfikacja
Więcej informacji
Terminy związane z tym badaniem
Dodatkowe istotne warunki MeSH
- Choroby Układu Nerwowego
- Nowotwory według lokalizacji
- Nowotwory
- Choroby nerwowo-mięśniowe
- Choroby Autoimmunologiczne
- Choroby układu odpornościowego
- Choroby Autoimmunologiczne Układu Nerwowego
- Choroby neurodegeneracyjne
- Zespoły Paraneoplastyczne, Układ Nerwowy
- Nowotwory Układu Nerwowego
- Zespoły paranowotworowe
- Choroby połączeń nerwowo-mięśniowych
- Myasthenia Gravis
Inne numery identyfikacyjne badania
Inne numery identyfikacyjne badania
- GRIT-CD-CHN-802-003
Informacje o lekach i urządzeniach, dokumenty badawcze
Bada produkt leczniczy regulowany przez amerykańską FDA
Bada produkt urządzenia regulowany przez amerykańską FDA
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