Clinical Trial of GenSci136 in Patients With Myasthenia Gravis
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase Ib/II Clinical Trial (Including an Open-Label Extension Phase) to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Administration of GenSci136 for Injection in Patients With Myasthenia Gravis
Phase Ib/II Clinical Trial of GenSci136 in Patients with Myasthenia Gravis
研究概览
详细说明
A Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase Ib/II Clinical Trial (Including an Open-Label Extension Phase) to Evaluate the Safety, Tolerability, Efficacy, Pharmacokinetics, and Pharmacodynamics of Subcutaneous Administration of GenSci136 for Injection in Patients with Myasthenia Gravis
研究类型
注册 (估计的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名：Chongbo Zhao
- 电话号码：+86 13701822316
- 邮箱：zhao_chongbo@fudan.edu.com
学习地点
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Shanghai Municipality
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Shanghai、Shanghai Municipality、中国、200032
- Huashan Hospital ,Fudan University
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Male or female, aged 18 to 70 years (both inclusive).
- standard-of-care (SoC) treatment for MG before screening.
- Men of reproductive age and women of childbearing potential must agree to take highly effective contraceptive methods from screening to 5 months after the last dose4. Participants who can understand the trial procedures, voluntarily participate in the trial (themselves or through their legally acceptable representative), For participants with gMG: 1. Participants diagnosed with gMG with generalized muscle weakness, corresponding to Myasthenia Gravis Foundation of America (MGFA) clinical classification Class II-IV
2. Positive for anti-AChR antibodies or anti-MuSK antibodies. 3. MG-ADL score must be ≥ 6, and the ocular score must account for < 50% of the total score. 4. QMG score must be ≥ 8, with at least 4 individual items scored ≥ 2. For participants with oMG: 1. Participants with a diagnosis of MG supported by the following medical documentation: a. Positive anti-AChR or anti-MuSK autoantibodies; or b. Abnormal neuromuscular transmission confirmed by single-fiber electromyography (SFEMG)/repetitive nerve stimulation (RNS), together with at least one of the following pharmacological/clinical confirmations: 1) documented positive ice pack test (resolution of ptosis after application of an ice pack to the eyelid for 2 minutes, with an improvement of > 2 mm); 2) documented positive edrophonium chloride (Tensilon) test, or a positive test with another cholinesterase inhibitor currently used in clinical practice to confirm oMG, such as the neostigmine test; or 3) documented improvement in MG signs following treatment with oral AChE inhibitors, plasma exchange, IVIg, glucocorticoids, or other relevant therapies. 2. Participants diagnosed with oMG, corresponding to MGFA clinical classification Class I. 3. the MGII (PRO) ocular score must be ≥ 6, and at least 2 ocular items must have a score of ≥ 2. 4. No pupillary abnormalities, except those caused by previous localized disease or surgery.
Exclusion Criteria:
- Known hypersensitivity to GenSci136 or any of the excipients contained in the GenSci136 formulation, or history of serious hypersensitivity reactions to any drug
- Participants with diseases or dysfunctions (excluding MG) known to interfere with the clinical trial,
- Participants with a known history of malignant tumors (including but not limited to lung cancer, colorectal cancer, liver cancer, gastric cancer, esophageal cancer, prostate cancer, thyroid cancer, bladder cancer, pancreatic cancer, kidney cancer, breast cancer, cervical cancer, corpus uteri cancer, ovarian cancer and malignant melanoma) are excluded unless they have been free of recurrence for ≥ 3 years; basal cell carcinoma, non-metastatic squamous cell carcinoma of the skin, cervical carcinoma in situ, breast carcinoma in situ, and incidental prostate cancer T1a/T1b are not excluded under this criterion (for thymoma-related requirements, see Exclusion Criterion 8).
- Presence of acute or chronic infections requiring treatment at screening.
- History of MG crisis within 1 month before screening.
- Diagnosis of any other autoimmune disease at screening other than MG, e.g., rheumatoid arthritis, Sjögren's syndrome (patients with abnormal thyroid function at screening will be excluded; those with autoimmune thyroiditis under stable control for ≥ 6 months and with normal thyroid function at screening may be exempted). 7. Participants who have attempted suicide within the past year or are currently at risk of impulsive behavior or suicide. 8. Participants with current or prior thymoma or thymectomy (except those meeting the criteria specified below), or planned thymectomy during the trial period. 9. Receipt of any live or live attenuated vaccine within 1 month before screening, or planned receipt of any live or live attenuated vaccine (except inactivated vaccine) during the trial period. 10. Receipt of intravenous, subcutaneous, or intramuscular immunoglobulin or plasma exchange within 1 month before screening. 11. Treatment with any form of CAR-T cell therapy, T-cell engager (TCE) therapy, or biologics targeting CD19/CD20 within 1 year before screening. 12. Positive hepatitis B virus at screening [hepatitis B surface antigen (HBsAg) positive; or HBsAg negative with hepatitis B core antibody (HBcAb) positive and hepatitis B virus deoxyribonucleic acid (HBV-DNA) positive or > upper limit of normal (ULN)], positive hepatitis C virus antibody (HCV-Ab), positive human immunodeficiency virus antibody (HIV-Ab), or positive syphilis serology test. 13. 12-lead ECG abnormalities during the screening period or at baseline, e.g., heart rate-corrected QT interval QTcF absolute value > 470 ms (Fridericia's formula: QTcF = QT/RR0.33) that, upon assessment by the investigator, may interfere with this clinical trial. 14. During the screening or baseline period, participants with any of the following abnormal laboratory test results: a) Absolute neutrophil count (ANC) < 1.2 × 10³/μL ; b) Platelet count < 75,000/μL (i.e., < 75 × 10⁹/L); c) Hemoglobin < 8.0 g/dL; d) IgG < 600 mg/dL; e) Creatinine > 1.5 × ULN or estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2; f) Glycated hemoglobin (HbA1c) > 8.0%, except for participants whose blood glucose control is considered adequate by the investigator; g) Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 × upper limit of normal (ULN), or total bilirubin (TBIL) > 1.5 × ULN; h) Other abnormal laboratory test results deemed by the investigator to make the participant unsuitable for participation in the study. 15. Participants judged by the investigator to be ineligible for other reasons.
学习计划
研究是如何设计的？
设计细节
- 主要用途：治疗
- 分配：随机化
- 介入模型：并行分配
- 屏蔽：双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：GenSci136 for injection
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GenSci136 for injection, administered the medication according to the requirements of the protocal |
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安慰剂比较：GenSci136 blank excipient(placebo) for injection
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GenSci136 for injection, administered the medication according to the requirements of the protocal |
研究衡量的是什么？
主要结果指标
结果测量 |
大体时间 |
|---|---|
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Changes from baseline in the incidence and severity of TEAEs/SAEs occurring within 10 weeks after the first dose and other safety measures (physical examination, vital signs, laboratory tests, 12-lead electrocardiogram [ECG], etc.).
大体时间：From time of informed consent to 10 weeks after the first dose of GenSci136
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From time of informed consent to 10 weeks after the first dose of GenSci136
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Changes from baseline in the incidence and severity of TEAEs/SAEs occurring within 10 weeks after the first dose and other safety measures (physical examination, vital signs, laboratory tests, 12-lead electrocardiogram [ECG], etc.).
大体时间：Approximately 26 weeks
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Approximately 26 weeks
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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area under the concentration-time curve from time 0 to time t of the last quantifiable concentration (AUC0-t)
大体时间：Approximately 10 weeks.
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Approximately 10 weeks.
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area under the concentration-time curve from time 0 to infinity (AUC0-∞)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
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area under the concentration-time curve from time 0 to time τ (AUC0-τ)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
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maximum concentration (Cmax)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
|
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time to maximum concentration (Tmax)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
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apparent clearance (CL/F)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
|
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apparent volume of distribution (Vd/F)
大体时间：Approximately 10 weeks
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Approximately 10 weeks
|
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Changes from baseline in free and total A proliferation-inducing ligand (APRIL) levels
大体时间：Approximately 10 weeks
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Approximately 10 weeks
|
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Changes from baseline in free and total B-cell activating factor (BAFF) levels
大体时间：Approximately 10 weeks
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Approximately 10 weeks
|
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Change from baseline in MG-ADL score at Week 48
大体时间：Approximately 48 Weeks
|
The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess the impact of myasthenia gravis symptoms on daily activities. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 24. Higher scores indicate greater disease severity and worse functional status. |
Approximately 48 Weeks
|
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Proportion of participants with a ≥ 2-point reduction from baseline in MG-ADL score at Week 26 and Week 48
大体时间：Approximately 48 Weeks
|
The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess the impact of myasthenia gravis symptoms on daily activities. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 24. Higher scores indicate greater disease severity and worse functional status. |
Approximately 48 Weeks
|
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Proportion of participants with a ≥ 3-point reduction from baseline in QMG score at Week 26 and Week 48
大体时间：Approximately 48 Weeks
|
The Quantitative Myasthenia Gravis (QMG) score is a 13-item clinician-administered measure used to assess muscle weakness and disease severity in patients with myasthenia gravis. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 39. Higher scores indicate greater disease severity and worse clinical outcomes. |
Approximately 48 Weeks
|
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Proportion of participants with minimal symptom expression (MSE, MG-ADL score of 0 or 1) at Week 26 and Week 48
大体时间：Approximately 48 Weeks
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Minimal symptom expression (MSE) is defined as a Myasthenia Gravis Activities of Daily Living (MG-ADL) total score of 0 or 1. The MG-ADL is an 8-item scale used to assess the impact of myasthenia gravis symptoms on daily activities. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 24, with higher scores indicating greater disease severity and worse functional status. |
Approximately 48 Weeks
|
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Change from baseline in total Myasthenia Gravis Composite (MGC) score at Week 26 and Week 4
大体时间：Approximately 26 Weeks
|
The Myasthenia Gravis Composite (MGC) is a validated 10-item assessment tool used to evaluate the clinical severity of myasthenia gravis, incorporating both physician-assessed and patient-reported measures. The total score ranges from 0 to 50, with higher scores indicating greater disease severity and worse clinical outcomes |
Approximately 26 Weeks
|
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Change from baseline in Revised Myasthenia Gravis Quality of Life-15 (MG-QoL15r) score at Week 26 and Week 48
大体时间：Approximately 48 Weeks
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The Revised 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r) is a patient-reported questionnaire used to assess the impact of myasthenia gravis on health-related quality of life. It consists of 15 items, each scored from 0 to 2, resulting in a total score ranging from 0 to 30. Higher scores indicate greater impairment in quality of life and worse clinical outcomes. |
Approximately 48 Weeks
|
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Change from baseline in EuroQol Five-Dimension Five-Level (EQ-5D-5L) score at Week 26 and Week 48
大体时间：Approximately 48 Weeks
|
The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire is a standardized measure of health-related quality of life comprising five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, ranging from 1 (no problems) to 5 (extreme problems). Responses are converted into a health utility index. The EQ Visual Analogue Scale (EQ-VAS) assesses participants' self-rated overall health status on a scale from 0 (worst imaginable health) to 100 (best imaginable health). Higher Index and EQ-VAS scores indicate better health status. |
Approximately 48 Weeks
|
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Change from baseline in MG-ADL score over time
大体时间：Approximately 48 Weeks
|
The Myasthenia Gravis Activities of Daily Living (MG-ADL) scale is an 8-item instrument used to assess the impact of myasthenia gravis symptoms on daily activities. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 24. Higher scores indicate greater disease severity and worse functional status. |
Approximately 48 Weeks
|
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Change from baseline in QMG score over time
大体时间：Approximately 48 Weeks
|
The Quantitative Myasthenia Gravis (QMG) score is a 13-item clinician-administered measure used to assess muscle weakness and disease severity in patients with myasthenia gravis. Each item is scored from 0 to 3, resulting in a total score ranging from 0 to 39. Higher scores indicate greater disease severity and worse clinical outcomes. |
Approximately 48 Weeks
|
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Change from baseline in MGC score over time
大体时间：Approximately 48 Weeks
|
The Myasthenia Gravis Composite (MGC) is a validated 10-item assessment tool used to evaluate the clinical severity of myasthenia gravis, incorporating both physician-assessed and patient-reported measures. The total score ranges from 0 to 50, with higher scores indicating greater disease severity and worse clinical outcomes. |
Approximately 48 Weeks
|
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Change from baseline in MG-QoL15r score over time
大体时间：Approximately 48 Weeks
|
The Revised 15-item Myasthenia Gravis Quality of Life Scale (MG-QoL15r) is a patient-reported questionnaire used to assess the impact of myasthenia gravis on health-related quality of life. It consists of 15 items, each scored from 0 to 2, resulting in a total score ranging from 0 to 30. Higher scores indicate greater impairment in quality of life and worse clinical outcomes. |
Approximately 48 Weeks
|
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Change from baseline in EQ-5D-5L score over time
大体时间：Approximately 48 Weeks
|
The EuroQol 5-Dimension 5-Level (EQ-5D-5L) questionnaire is a standardized measure of health-related quality of life comprising five dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has five response levels, ranging from 1 (no problems) to 5 (extreme problems). Responses are converted into a health utility index. The EQ Visual Analogue Scale (EQ-VAS) assesses participants' self-rated overall health status on a scale from 0 (worst imaginable health) to 100 (best imaginable health). Higher Index and EQ-VAS scores indicate better health status. |
Approximately 48 Weeks
|
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Change from baseline in ocular score of the Myasthenia Gravis Impairment Index (participant-reported outcomes) [MGII (PRO)] at Week 26 and Week 48
大体时间：Approximately 48 weeks
|
The Myasthenia Gravis Impairment Index (MGII) is a validated measure of myasthenia gravis disease severity comprising 22 patient-reported outcome (PRO) items and 6 physical examination (PE) items. The MGII ocular PRO score consists of 6 patient-reported items assessing the frequency, severity, and impact of diplopia and ptosis. Each item is scored from 0 to 3, yielding a total ocular PRO score ranging from 0 to 18. Higher scores indicate more severe ocular symptoms. |
Approximately 48 weeks
|
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Change from baseline in ocular score of the Myasthenia Gravis Impairment Index (Participant-reported Outcome and Physical Examination) (MGII [PRO+PE]) at Week 26 and Week 48
大体时间：Approximately 48 weeks
|
The Myasthenia Gravis Impairment Index (MGII) is a validated measure of myasthenia gravis disease severity comprising 22 patient-reported outcome (PRO) items and 6 physical examination (PE) items. The MGII ocular PRO+PE score combines 6 patient-reported items and 2 clinician-assessed physical examination items evaluating diplopia and ptosis. The score is calculated as the sum of these 8 items, ranging from 0 to 23. Higher scores indicate more severe ocular impairment |
Approximately 48 weeks
|
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Change from baseline in ocular score of the MGII (PE) at Week 26 and Week 48
大体时间：Approximately 48 weeks
|
The Myasthenia Gravis Impairment Index (MGII) is a validated measure of myasthenia gravis disease severity comprising patient-reported and physical examination components. The MGII ocular physical examination (PE) score consists of 2 clinician-assessed items evaluating diplopia (scored from 0 to 3) and ptosis (scored from 0 to 2). The total ocular PE score ranges from 0 to 5, with higher scores indicating more severe ocular impairment. |
Approximately 48 weeks
|
|
Changes from baseline in total MGII score at Week 26 and Week 48
大体时间：Approximately 48 weeks
|
Approximately 48 weeks
|
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Changes from baseline in the incidence and severity of TEAEs
大体时间：Approximately 64 weeks
|
The Myasthenia Gravis Impairment Index (MGII) is a validated measure of myasthenia gravis disease severity comprising 28 items, including 22 patient-reported outcome (PRO) items and 6 physical examination (PE) items. The MGII evaluates ocular and generalized impairments, including symptoms affecting ocular, bulbar, respiratory, and limb muscle function. The total score is calculated as the sum of all 28 items and ranges from 0 to 84. Higher scores indicate greater disease severity and impairment. |
Approximately 64 weeks
|
|
Changes from baseline in the incidence and severity of SAEs
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
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steady-state maximum concentration (Cmax, ss)
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
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steady-state trough concentration (Cmin, ss)
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
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time to steady-state maximum concentration (Tmax, ss)
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
|
mean concentration at steady state (Cav, ss)
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
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area under the concentration-time curve over the dosing interval at steady state (AUC0-τ, ss)
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
|
Changes from baseline in free and total APRIL levels
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
|
|
Changes from baseline in free and total BAFF levels
大体时间：Approximately 64 weeks
|
Approximately 64 weeks
|
合作者和调查者
调查人员
- 首席研究员：Sushan Luo、Huashan Hospital
- 首席研究员：Bitao Bu、Tongji Hospital
研究记录日期
研究主要日期
学习开始 (估计的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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