2024-513589-20-00招募中2 期
An open-label, multi-center, phase I/II study to assess safety, efficacy, and cellular kinetics of YTB323 in participants with treatment-resistant generalized myasthenia gravis
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 3
- 试验地点
- 5
- 主要终点
- Occurrence, severity, and frequency of Adverse Events (AEs) (including CRS and ICANs) and change from baseline in safety parameters including, but not limited to: Vital signs, laboratory parameters, ECG, and neurological status
研究概览
简要总结
To assess the safety of YTB323 in patients with treatment-resistant generalized myasthenia gravis (gMG) with antibodies against AChR or MuSK.
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Signed informed consent, and able to communicate well with the investigator and comply with the requirements of the study
- •Male or female participants 18-65 years of age with adequate renal, hepatic, cardiac, hematological, and pulmonary function (see definitions in Section 5.1)
- •Confirmed gMG diagnosis with documented positive AChR antibodies or MuSK antibodies at screening AND has one of the following: history of abnormal neuromuscular transmission test demonstrated by repetitive nerve stimulation or single-fiber electromyography OR history of positive acetylcholinesterase test OR improvement in MG signs on an oral acetylcholinesterase inhibitor as assessed by the treating physician
- •Generalized myasthenia gravis classified as MGFA Class III-IVa at screening
- •Treatment-resistant gMG as defined by: MG-ADL score ≥6 at screening despite adequate treatment trials with at least two different non-steroidal immunosuppressive drugs given at adequate doses and duration of therapy. Specifically, they must have failed treatment with at least one oral immunomodulatory or steroid-sparing drug (e.g., azathioprine, mycophenolate mofetil, tacrolimus) AND EITHER one approved anti-C5 complement antibody (e.g., eculizumab, ravulizumab) OR an approved FcRn antagonist OR rituximab, OR required two or more rescue therapies (plasma exchange/immunoadsorption or IVIg) for myasthenic worsening/crisis in the 12 months before screening
- •If on chronic corticosteroids, ability and willingness to taper to a maximum dose at least one week before leukapheresis
排除标准
- •Exclusively ocular myasthenia gravis (MGFA I), mild symptoms (MGFA II), or severe bulbar disease or MG crisis, MGFA Class IVb or V (at time of screening)
- •Clinically significant active, opportunistic, chronic or recurrent infection (including positive for hepatitis B or hepatitis C, HIV or TB)
- •History of malignancy of any organ system (other than complete resection of localized basal cell carcinoma of the skin or in situ cervical cancer or non-invasive malignant polyps that have been removed), treated or untreated, within the past 5 years
- •Known thymic neoplasm or history of thymectomy within 12 months prior to screening
- •Prior treatment with anti-CD19 therapy, adoptive T cell therapy or any prior gene therapy product (e.g. CAR-T cell therapy)
- •Hypersensitivity and/or contraindications to any product (including its ingredients) to be given to the participant as per the study protocol (e.g., YTB323, tocilizumab, lymphodepleting agents, etc.) or any condition that, in the Investigator's opinion, precludes lymphodepleting chemotherapy
结局指标
主要结局
Occurrence, severity, and frequency of Adverse Events (AEs) (including CRS and ICANs) and change from baseline in safety parameters including, but not limited to: Vital signs, laboratory parameters, ECG, and neurological status
Occurrence, severity, and frequency of Adverse Events (AEs) (including CRS and ICANs) and change from baseline in safety parameters including, but not limited to: Vital signs, laboratory parameters, ECG, and neurological status
次要结局
- YTB323 transgene levels by qPCR over time in peripheral blood; cellular kinetics parameters (Cmax, AUC, Tmax, Clast, Tlast)
- Pre-existing and treatment induced immunogenicity (cellular, humoral, neutralizing antibodies) of YTB323
- At various timepoints: • Change from BL of MG-ADL score • Change from BL of QMG total score • Whether or not patient achieves a ≥3-point reduction of QMG total score sustained for 6 months post BL • Whether or not patient achieves a ≥2-point reduction of MG-ADL score sustained for 6 months post BL • Whether or not a patient achieves MGFA Post intervention Status (PIS) of minimal manifestations (MM) or better and sustained for 6 months post BL
- Manufacture success (defined as meeting release specifications and target dose)
研究者
Novartis Pharma Arzneimittel GmbH
Scientific
Novartis Pharma AG
研究点 (5)
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