Refractory Myasthenia Gravis
Conditions
Keywords
MG, HN2302
Brief summary
This is an open label, single arm study, to evaluate the safety , tolerability and preliminary efficacy of HN2302 for refractory myasthenia gravis.
Detailed description
The study will consist of an up to 4-week Screening Period, Treatment Period and one year Follow-up Period.
Interventions
DRUGHN2302 Injection
Patients will be administrated with specified dose on specified days at a lower dose level and escalated to safe and effective dose levels.
Sponsors
The Affiliated Hospital of Xuzhou Medical University
Shenzhen MagicRNA Biotechnology Co., Ltd
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; * 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 | Up to 3 months | Proportion and severity of adverse events (AEs) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes from baseline in 15-item quality of life (MG-QOL15r) score | 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). |
| 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. |
| Percentage of patients with symptom changes after treatment | Up to 12 months | Proportion of patients without symptom worsening or relapse |
| in vivo CAR T cell production | Day-28 to14 days | Assessment of CAR T production (CAR expression ratio in T cells) in the peripheral blood of MG patients by flow cytometry (FACS) |
| B cell ratio and counts in peripheral blood | Up to 12 months | Assessment of B cell ratio and counts (B cell counts per μl peripheral blood) and B cell subsets(naive B cell, memory B cell) by flow cytometry (FACS) in peripheral blood |
| Dynamic changes in cytokine levels after treatment | Up to 12 months | Differences in cytokine post-administration vs. baseline |
| 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. |
| Changes in acetylcholine receptor (AchR) antibody levels after treatment | Up to 12 months | Differences in AchR antibody post-administration vs. baseline |
Countries
China
Contacts
CONTACTYong Zhang
PRINCIPAL_INVESTIGATORGuiyun Cui
The Affiliated Hospital of Xuzhou Medical University
PRINCIPAL_INVESTIGATORYong Zhang
The Affiliated Hospital of Xuzhou Medical University
Outcome results
None listed