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.
調査の概要
詳細な説明
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.
研究の種類
入学 (推定)
段階
- 初期フェーズ 1
連絡先と場所
研究連絡先
- 名前:Yuhang Cheng
- 電話番号:+86 13125197960
- メール:chengyh_tj@163.com
研究場所
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Hubei
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Wuhan、Hubei、中国、430000
- Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
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主任研究者:
- Daishi Tian
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主任研究者:
- Chuan Qin
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コンタクト:
- Daishi Tian
- 電話番号:+86 13607178809
- メール:tiands@tjh.tjmu.edu.cn
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
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.
研究計画
研究はどのように設計されていますか?
デザインの詳細
- 主な目的:処理
- 割り当て:なし
- 介入モデル:単一グループの割り当て
- マスキング:なし(オープンラベル)
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
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実験的:GT802 Injection treatment group
Participants with MG administered GT802 Injection |
Injection |
この研究は何を測定していますか?
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Adverse Events (AEs) occurring after infusion and their proportions
時間枠: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
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Quantitative Myasthenia Gravis (QMG) score
時間枠: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
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Myasthenia Gravis Activities of Daily Living (MG-ADL) score
時間枠: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)
時間枠: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)
時間枠: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)
時間枠:From infusion to 12 months
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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)
時間枠: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
時間枠: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.
時間枠: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
|
協力者と研究者
スポンサー
捜査官
- 主任研究者:Chuan Qin、Tongji Hospital
- 主任研究者:Daishi Tian、Tongji Hospital
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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