Efficacy and Safety of HN2301 in Refractory Myasthenia Gravis(MG)

Dose-escalation Study to Assess the Safety, Tolerability, and Preliminary Efficacy of HN2301 in Patients With Refractory Myasthenia Gravis (MG)

This is an investigator-initiated trial designed to evaluate the safety, and efficacy of HN2301 in refractory myasthenia gravis

Study Overview

• Status: Terminated
• Conditions: Refractory Myasthenia Gravis
• Intervention / Treatment: Drug: HN2301 injection

Detailed Description

This study is a prospective exploratory clinical trial in subjects with refractory myasthenia gravis. The objective is to evaluate the safety, initial efficacy of HN2301injection in refractory myasthenia gravis.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201600
    • Shanghai General Hospital (Songjiang Branch) of Shanghai Jiao Tong University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 (Myasthenia Gravis Activities of Daily Living) score ≥6, with ocular-related score <50%;
• Poor response and/or lack of effective treatment under standard therapies, defined as no improvement or worsening of symptoms despite stable treatment with corticosteroids, immunosuppressants (e.g., azathioprine, mycophenolate mofetil, tacrolimus, cyclosporin A, cyclophosphamide), or rituximab;
• Expected survival time greater than 12 weeks;
• Adequate bone marrow, coagulation, cardiopulmonary, liver, and renal function；Bone marrow function: ANC ≥1.5×10⁹/L, ALC ≥0.8×10⁹/L, Hb ≥80g/L; transfusions or growth factors must not be used within 7 days prior to screening to meet these criteria.Coagulation function: INR or APTT ≤1.5×ULN.
• Cardiac function: left ventricular ejection fraction (LVEF) ≥40% assessed by echocardiogram (ECHO).
• Pulmonary function: CTCAE grade ≤1 dyspnea and room air SpO₂ ≥92% (measured by pulse oximetry).
• Liver function: ALT and AST ≤2.5×ULN; total bilirubin <2.0 mg/dL (or <3.0 mg/dL for subjects with Gilbert's syndrome).
• Renal function: calculated creatinine clearance (Cockcroft-Gault) ≥50 mL/min without hydration assistance.

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 upper 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: HN2301 treatment group; Specified dose level	Drug: HN2301 injection; Description: Three dose groups were set up, starting from the low dose group and climbing to explore the safe and effective dose.; Other Names: in vivo cart

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse events related to HN2301	Incidence and severity of AEs associated with HN2301 as assessed by CTCAE v5.	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
B cell ratio and counts in peripheral blood	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	Day-28 to12 months
vivo CAR T cell production	Assessment of CAR T production (CAR expression ratio in T cells) in the peripheral blood of MG patients by flow cytometry (FACS)	Day-28 to14 days
Change from baseline of MG-ADL score after HN2301 administration.	Assessment of MG-ADL score from baseline administration at various timepoints up to month 12 follow-up visit. A total score can fall between 0 and 24 with a higher score representing a more significant degree of disease activity.; Proportion of patients achieving a ≥2-point reduction in MG-ADL score following HN2301 administration.	Day-28 to12 months
Change from baseline of MGC score after HN2301 administration.	Assessment of MGC score from baseline administration at various timepoints up to month 12 follow-up visit. A total score can fall between 0 and 50 with a higher score representing a more significant degree of disease activity.; Proportion of patients achieving a ≥3-point reduction in MGC score following HN2301 administration.	Day-28 to12 months
Change from baseline of QMG score after HN2301 administration.	Assessment of QMG from baseline administration at various timepoints up to month 12 follow-up visit. A total score can fall between 0 and 32, with a higher score representing a more significant degree of disease activity.; Proportion of patients achieving a ≥3-point reduction in QMG score following HN2301 administration.	Day-28 to12 months
Change from baseline of MG-QOL15r score after HN2301 administration.	Assessment of MG-QOL15r from baseline administration at various timepoints up to month 12 follow-up visit. A total score can fall between 0 and 100, with a lower score representing a more significant degree of disease activity.	Day-28 to12 months
Change of patients after HN2301 administration.	Proportion of patients without symptom worsening; Proportion of patients without symptom relapse; Proportion of patients achieving minimal clinical manifestations; Proportion of patients undergoing corticosteroid dose reduction	Day-28 to12 months
Time to achieve a ≥2 point reduction in MG-ADL score following HN2301 administration.	The time (months) to achieve a ≥2 point reduction in MG-ADL score following HN2301 administration of the patient.	14 days-12 months

Collaborators and Investigators

• Sponsor: Shenzhen MagicRNA Biotechnology Co., Ltd
• Collaborators: Shanghai General Hospital (Songjiang Branch)
• Investigators: Principal Investigator: Ailian Du, Shanghai Songshan Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2026
• Primary Completion (Actual): February 11, 2026
• Study Completion (Actual): February 11, 2026

Study Registration Dates

• First Submitted: April 29, 2025
• First Submitted That Met QC Criteria: May 7, 2025
• First Posted (Actual): May 11, 2025

Study Record Updates

• Last Update Posted (Actual): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 10, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neoplasms by Site; Neoplasms; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases; Autoimmune Diseases of the Nervous System; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Paraneoplastic Syndromes; Neuromuscular Junction Diseases; Myasthenia Gravis
• Other Study ID Numbers: HN2301-002

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No