A Study to Evaluate the Efficacy, Safety and PD and PK of HBM9161 in MG Patients

A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety and Pharmacodynamic and Pharmacokinetic of HBM9161 (HL161) Subcutaneous Injection in Patients With Generalized Myasthenia Gravis

This is a multicenter, randomized, double-blind and placebo-controlled study. The investigational drug is HBM9161 injection, and the indication is MG. The subjects will be randomized to three dose groups (340mg, 680mg and placebo) for a 6 weeks' double-blind treatment period followed by an open-label extension treatment period. The study will investigate the safety, efficacy and pharmacodynamic and pharmacokinetic of HBM9161 in patients with attack of MG in China.

The MG-ADL profile provides an assessment of MG symptom severity and measures 8 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the ADL score. The ADL score can range from 0 (least severe) to 24 (most severe)

The total QMG score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity.

The QMG test is a standardized quantitative strength scoring system and measures 13 items on a 0-3 scale, with 0 being the least severe. The total sum of the 13 items represents the QMG score. The QMG score can range from 0 (least severe) to 39 (most severe).

The MG-QoL 15r scale is a patient-reported score that assesses the patient's perception of impairment and disability and the degree to which the patient tolerates disease manifestations. Each question was graded on a 3-point scale from 0=normal to 2=severe with a score of 0 to 30; the higher score indicates worse MG disease activity

Proportion of participants with an improvement and worse on the MGFA Post-intervention Status (MGFA-PIS) from baseline to Day 43. o Improvement: MGC Score reduce ≥ 3 points o Aggravation: MGC Score increase ≥ 3 points

Inclusion Criteria: Signed Informed Consent Form. Male or female ≥ 18 years of age. A female participant is eligible to participate if she is of: Non-childbearing potential (physically infertile, including women who have been menopausal for 2 years or more); Childbearing potential, negative serum pregnancy test results at screening visits, and agree to consistently use acceptable and effective contraceptive methods until 14 days after the final visit. A male participant must take effective contraception during this clinical trial or their heterosexual partner must take effective contraception. Meets MGFA myasthenia gravis clinical classification IIa-IVa (includes types IIa, IIb, IIIa, IIIb, and IVa) at the screening visit and at the baseline visit. Screening and baseline MG-ADL score ≥ 6, and < 50% of them is from ocular muscle. Stable background MG treatments at randomization. Positive serologic test for AChR-Ab or MUSK-Ab at the screening visit and at least 1 of the following: History of abnormal neuromuscular transmission test demonstrated by sign-fiber-electromyography or repetitive nerve stimulation OR History of positive edrophonium chloride test OR Participant has demonstrated improvement in MG signs on oral cholinesterase inhibitors as assessed by the treating physician. Exclusion Criteria: Use of rituximab, belimumab, eculizumab or any monoclonal antibody/Fc-fusion biologic for immunomodulation within 6 months prior to screening. Immunoglobulins given by SC, IV(IVIG), or intramuscular route, or plasmapheresis/plasma exchange (PE) within 4 weeks before screening. Thymectomy performed < 12 months prior to screening. Total IgG level <6g/L (at screening). Participant has any laboratory abnormality (at screening) that, in the opinion of the investigator, is clinically significant, has not resolved at baseline, and could jeopardize or would compromise the participant's ability to participate in this study. Have known autoimmune disease other than MG that would interfere with the course and conduct of the study (such as uncontrolled thyroid disease). Have an active infection, a recent serious infection (i.e., requiring injectable antimicrobial therapy or hospitalization) within the 8 weeks prior to screening. History of or known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), or Mycobacterium tuberculosis. Participants must have negative test results for HBV surface antigen, HBV core antibody, HCV antibody, HIV 1 and 2 antibodies and a negative TB test at screening.

Yan C, Duan RS, Yang H, Li HF, Zou Z, Zhang H, Zhou H, Li XL, Zhou H, Jiao L, Chen J, Yin J, Du Q, Lee M, Chen Y, Chen X, Zhao C. Therapeutic Effects of Batoclimab in Chinese Patients with Generalized Myasthenia Gravis: A Double-Blinded, Randomized, Placebo-Controlled Phase II Study. Neurol Ther. 2022 Jun;11(2):815-834. doi: 10.1007/s40120-022-00345-9. Epub 2022 Apr 12.