Clinical trial NCT06965309: Efficacy and Safety of HN2301 in Refractory Myasthenia Gravis(MG)
Official title: Dose-escalation Study to Assess the Safety, Tolerability, and Preliminary Efficacy of HN2301 in Patients With Refractory Myasthenia Gravis (MG)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Refractory Myasthenia Gravis
Lead sponsor: Shenzhen MagicRNA Biotechnology Co., Ltd
Sponsor class: INDUSTRY
Collaborators: name: Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
First posted: 2025-05-11
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Adverse events related to HN2301
timeFrame: 3 months
Secondary outcomes:
measure: vivo CAR T cell production
timeFrame: Day-28 to14 days
measure: B cell ratio and counts in peripheral blood
timeFrame: Day-28 to12 months
measure: Change from baseline of MG-ADL score after HN2301 administration.
timeFrame: Day-28 to12 months
measure: Change from baseline of MGC score after HN2301 administration.
timeFrame: Day-28 to12 months
measure: Change from baseline of QMG score after HN2301 administration.
timeFrame: Day-28 to12 months
measure: Change from baseline of MG-QOL15r score after HN2301 administration.
timeFrame: Day-28 to12 months
measure: Change of patients after HN2301 administration.
timeFrame: Day-28 to12 months
measure: Time to achieve a ≥2 point reduction in MG-ADL score following HN2301 administration.
timeFrame: 14 days-12 months
Other outcomes:
Locations:
city: Shanhai
country: China
facility: Shanghai General Hospital (Songjiang Branch) of Shanghai Jiao Tong University School of Medicine
Study officials:
References: