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.
Studienübersicht
Status
Status
Bedingungen
Bedingungen
Intervention / Behandlung
Intervention / Behandlung
Detaillierte Beschreibung
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.
Studientyp
Studientyp
Einschreibung (Geschätzt)
Einschreibung
Phase
Phase
- Frühphase 1
Kontakte und Standorte
Studienkontakt
Studienkontakt
- Name: Yuhang Cheng
- Telefonnummer: +86 13125197960
- E-Mail: chengyh_tj@163.com
Studienorte
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Hubei
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Wuhan, Hubei, China, 430000
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
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Hauptermittler:
- Daishi Tian
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Hauptermittler:
- Chuan Qin
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Kontakt:
- Daishi Tian
- Telefonnummer: +86 13607178809
- E-Mail: tiands@tjh.tjmu.edu.cn
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Teilnahmekriterien
Zulassungskriterien
Zulassungskriterien
Studienberechtigtes Alter
Akzeptiert gesunde Freiwillige
Studienberechtigte Geschlechter
Beschreibung
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.
Studienplan
Wie ist die Studie aufgebaut?
Designdetails
- Hauptzweck: Behandlung
- Zuteilung: N / A
- Interventionsmodell: Einzelgruppenzuweisung
- Maskierung: Keine (Offenes Etikett)
Anzahl der Arme
Waffen und Interventionen
Teilnehmergruppe / ArmTeilnehmergruppe / Arm |
Intervention / BehandlungIntervention / Behandlung |
|---|---|
|
Experimental: GT802 Injection treatment group
Participants with MG administered GT802 Injection |
Injection |
Was misst die Studie?
Primäre Ergebnismessungen
Primäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Adverse Events (AEs) occurring after infusion and their proportions
Zeitfenster: From infusion to at least 1 year
|
Adverse Events (AEs) occurring after infusion and their proportions |
From infusion to at least 1 year
|
Sekundäre Ergebnismessungen
Sekundäre Ergebnismessungen
Ergebnis Maßnahme |
Maßnahmenbeschreibung |
Zeitfenster |
|---|---|---|
|
Quantitative Myasthenia Gravis (QMG) score
Zeitfenster: 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
Zeitfenster: 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)
Zeitfenster: From infusion to 12 months
|
Time to maximum amplification (Tmax) of cells following GT802 infusion |
From infusion to 12 months
|
|
Maximum amplification (Cmax)
Zeitfenster: 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)
Zeitfenster: From infusion to 12 months
|
Area under the curve (AUC) of cellular expansion following GT802 infusion |
From infusion to 12 months
|
|
Duration of Detectable Concentration (Tlast)
Zeitfenster: 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
Zeitfenster: From infusion to 2 months
|
Monitor serum cytokine levels after infusion |
From infusion to 2 months
|
|
Anti-drug antibodies (ADA) Response to GT802 Measured by Immunoassay.
Zeitfenster: From infusion to 12 months
|
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
|
Mitarbeiter und Ermittler
Sponsor
Sponsor
Mitarbeiter
Mitarbeiter
Ermittler
Ermittler
- Hauptermittler: Chuan Qin, Tongji Hospital
- Hauptermittler: Daishi Tian, Tongji Hospital
Studienaufzeichnungsdaten
Haupttermine studieren
Studienbeginn (Geschätzt)
Studienbeginn
Primärer Abschluss (Geschätzt)
Primärer Abschluss
Studienabschluss (Geschätzt)
Studienabschluss
Studienanmeldedaten
Zuerst eingereicht
Zuerst eingereicht
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst eingereicht, das die QC-Kriterien erfüllt hat
Zuerst gepostet (Tatsächlich)
Zuerst gepostet
Studienaufzeichnungsaktualisierungen
Letztes Update gepostet (Tatsächlich)
Letztes Update gepostet
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Letztes eingereichtes Update, das die QC-Kriterien erfüllt
Zuletzt verifiziert
Zuletzt verifiziert
Mehr Informationen
Begriffe im Zusammenhang mit dieser Studie
Zusätzliche relevante MeSH-Bedingungen
- Erkrankungen des Nervensystems
- Neubildungen nach Standort
- Neubildungen
- Neuromuskuläre Erkrankungen
- Autoimmunerkrankungen
- Erkrankungen des Immunsystems
- Autoimmunerkrankungen des Nervensystems
- Neurodegenerative Krankheiten
- Paraneoplastische Syndrome, Nervensystem
- Neubildungen des Nervensystems
- Paraneoplastische Syndrome
- Erkrankungen der neuromuskulären Verbindungen
- Myasthenia gravis
Andere Studien-ID-Nummern
Andere Studien-ID-Nummern
- GRIT-CD-CHN-802-003
Arzneimittel- und Geräteinformationen, Studienunterlagen
Studiert ein von der US-amerikanischen FDA reguliertes Arzneimittelprodukt
Studiert ein von der US-amerikanischen FDA reguliertes Geräteprodukt
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