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

Study Overview
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Brief Summary
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Primary Objectives: To investigate the efficacy of HBM9161 in patients with attack of MG in China

Detailed Description
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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.

Official Title
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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

Conditions
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Myasthenia Gravis

Intervention / Treatment
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* Drug: HBM9161 Injection (680mg and 340 mg)
* Drug: Placebos
* Drug: HBM9161 Injection (340 mg)


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: HBM9161 (680mg and 340 mg)<br>Subcutaneous injection; Blinded: HBM9161 680mg; Open-label: HBM9161 340mg; | Drug: HBM9161 Injection (680mg and 340 mg)<br>* HBM9161 Injection (680mg and 340mg)<br>|
| Experimental: HBM9161 (340 mg)<br>Subcutaneous injection; Blinded: HBM9161 340mg; Open-label: HBM9161 340mg; | Drug: HBM9161 Injection (340 mg)<br>* HBM9161 Injection (340 mg)<br>|
| Placebo Comparator: Placebo, HBM9161 (340 mg)<br>Subcutaneous injection; Blinded: Placebo; Open-label: HBM9161 340mg; | Drug: Placebos<br>* Placebo, HBM9161 Injection (340mg)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score from baseline to Day 43 | 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) | 43 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the Myasthenia Gravis Composite (MGC) score from baseline to Day 43 | 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. | 43 days | 
| Change in the Quantitative Myasthenia Gravis (QMG) score from baseline to Day 43 | 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). | 43 days | 
| Change in the Myasthenia Gravis Quality of Life 15(MG-QoL15r) score from baseline to Day 43 | 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 | 43 days | 
| Proportion of participants with a decrease on the MG-ADL Score by ≥ 2 points from baseline to Day 43 |  | 43 days | 
| 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 |  | 43 days | 
| Change in the MG-ADL score from baseline to Day 120 |  | 120 days | 
| Change in the MGC score from baseline to Day 120 |  | 120 days | 
| Change in the QMG score from baseline to Day 120 |  | 120 days | 
| Change in the MG-QoL15r score from baseline to Day 120 |  | 120 days | 
| Proportion of participants with persistent improvement on the MGC score from baseline to Day 120 | Improvement (decrease) in the MGC score by ≥ 3 points for 6 weeks | 120 days | 
| Proportion of participants with persistent improvement on the MG-ADL score from baseline to Day 120 | Improvement (decrease) in the MG-ADL Score by ≥ 2 points for 6 weeks | 120 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MG