Generalized Myasthenia Gravis
Conditions
Keywords
MG, in vivo CART
Brief summary
This is an open label, single arm study, to evaluate safety, tolerability and preliminary efficacy of HN2301 in patients with Generalized Myasthenia Gravis.
Detailed description
This study consists of a screening period of up to 4 weeks, a treatment period, and a follow-up period of 1 year.
Interventions
DRUGHN2301 injection
Dosing will begin at a lower dose level and may be escalated to dose levels considered safe and potentially effective according to the study protocol.
Sponsors
Shenzhen MagicRNA Biotechnology Co., Ltd
The First Affiliated Hospital of University of Science and Technology of China
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age: 18-80 years, no gender restriction; * Confirmed diagnosis of generalized myasthenia gravis (MG) with positive AchR or MuSK antibodies, meeting at least one of the following conditions#(1) Repetitive nerve stimulation suggesting neuromuscular transmission defect; (2) Positive response to neostigmine test; (3) Clinically judged improvement of --MG symptoms after oral cholinesterase inhibitor therapy; * Clinical classification of MG according to MGFA types IIa-IVb (including IIa, IIb, IIIa, IIIb, IVa, IVb); * Baseline MG-ADL score ≥6, ocular-related score \<50%; * Poor response and/or lack of efficacy under standard therapies; * Minimum life expectancy \> 12 weeks; * Adequate bone marrow, coagulation, cardiopulmonary, liver, and renal function.
Exclusion criteria
* Subjects positive for hepatitis B surface antigen (HBsAg) and/or hepatitis B core antibody (HBcAb) with detectable or quantifiable HBV DNA, positive for hepatitis C antibody (HCV Ab) with detectable or quantifiable HCV RNA, positive for HIV antibody, positive CMV DNA, or CMV DNA above the lower limit of detection; positive for syphilis antigen or antibody; * Presence of other uncontrolled active infections; * History of major organ transplantation (e.g., heart, lung, liver, kidney) or bone marrow/hematopoietic stem cell transplantation; * Pregnant or breastfeeding women; * Receipt of any mRNA-LNP products or other LNP-based drugs within the past two years; * History of any of the following cardiovascular conditions within 6 months prior to screening: New York Heart Association (NYHA) Class III or IV heart failure, myocardial infarction, unstable angina, uncontrolled or symptomatic atrial arrhythmias, any ventricular arrhythmias, or other clinically significant cardiac disease; * History of ≥Grade 2 bleeding events within 30 days prior to screening, or requiring long-term continuous anticoagulation therapy (e.g., warfarin, low molecular weight heparin, Xa factor inhibitors); * History of live vaccination within 30 days prior to screening; * Severe central nervous system diseases or pathological changes, including but not limited to: cerebrovascular accident, aneurysm, epilepsy, seizures/convulsions, aphasia, stroke, severe brain injury, dementia, Parkinson's disease, cerebellar disorders, organic brain syndromes, or psychosis; * History of asthma or severe allergies; * Patients combined with other malignant tumors; * Any condition that, in the investigator's opinion, may increase the patient's risk or interfere with study assessments.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of treatment-emergent adverse events (TEAEs) | Up to 3 months | Incidence, nature, and severity of treatment-emergent adverse events, assessed according to the study protocol and applicable toxicity grading criteria. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| in vivo CAR T cell production | Up to14 days | Assessment of in vivo CAR-T cell production, defined by the proportion of CAR-expressing T cells in peripheral blood as measured by flow cytometry. |
| Absolute B-cell count in peripheral blood | Up to 12 months | Assessment of peripheral blood absolute B-cell count (cells/μL)， including naive B cells and memory B cells, by flow cytometry. |
| Changes from baseline in Myasthenia Gravis Activities of Daily Living(MG-ADL) score | Up to 12 months] | Proportion of patients ≥2 points. A total score can fall between 0 and 24, with a higher score representing a more significant degree of disease activity. |
| Changes from baseline in Myasthenia Gravis Composite (MGC) score | Up to 12 months | Proportion of patients ≥3-point reduction.The total score is 50 points. The higher the score, the more severe the condition is indicated. |
| Changes from baseline in Quantitative Myasthenia Gravis (QMG) score | Up to 12 months] | Proportion of patients ≥3-point reduction. To assess the muscle strength and endurance of the affected muscles in patients with myasthenia gravis, thereby reflecting the severity of the disease，including 8 items, each scored on a scale of 0 to 3, with 3 indicating the most severe degree. |
| Changes from baseline in revised Myasthenia Gravis Quality of Life-15 score (MG-QOL15r) | Up to 12 months | To assess important aspects of the patient's experience related to MG, scores each of 15 items 0-2 (max score 30).The higher the score, the worse the patient's quality of life. |
| Changes in acetylcholine receptor (AchR) antibody levels after treatment | Up to 12 months | Differences in AchR antibody post-administration vs. baseline |
Countries
China
Contacts
CONTACTZexiu Xiao
PRINCIPAL_INVESTIGATORWen Xu
The First Affiliated Hospital of University of Science and Technology of China
PRINCIPAL_INVESTIGATORYan Jiang
The First Affiliated Hospital of University of Science and Technology of China
CONTACTWen Xu
Outcome results
None listed