Generalized Myasthenia Gravis
Conditions
Brief summary
This study is a multicenter, randomized, double-blind, placebo-controlled Phase II clinical trial designed to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of SHR-2173 compared to placebo as an add-on therapy to standard of care (SOC) for the treatment of generalized myasthenia gravis (gMG). The study consists of a 4-week screening period, a 24-week treatment period, and a 12-week safety follow-up period.
Interventions
SHR-2173 injection；High dose
DRUGPlacebo
Placebo
Sponsors
Guangdong Hengrui Pharmaceutical Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
1. Male and female participants aged 18-75 years, confirmed diagnosis of generalized myasthenia gravis (gMG) (Myasthenia Gravis Foundation of America \[MGFA\] class II-IV). 2. Positive for anti-AChR antibody or anti-MuSK antibody. 3. MG-ADL total score ≥5 at screening and baseline, with \>50% of the score attributable to non-ocular items. 4. QMG score ≥11 at screening and baseline. 5. Maintenance on stable standard of care (SOC) therapy. 6. No contraindication to at least one rescue therapy: IVIg or PLEX. 7. Provided written informed consent (ICF) after full understanding of the study content, procedures, and potential adverse reactions. 8. Female subjects with fertility or male participants whose partners are women of childbearing age must avoid donating sperm/eggs from the date of signing the ICF until 12 weeks after the last study medication, and agree to take contraceptive measures as specified in the protocol
Exclusion criteria
1. Presence of any of the following medical histories or comorbidities: 1. Any untreated thymic epithelial tumor, mediastinal germ cell tumor, or other malignant mediastinal mass; or any thymic cyst or other mass requiring immediate intervention per investigator judgment; 2. Previous history of thymic tumor not meeting protocol requirements; 3. Myasthenic crisis (MGFA Class V) within 3 months prior to randomization; 4. Any known disease other than gMG that may interfere with study procedures and assessments; 5. A history of progressive multifocal leukoencephalopathy (PML); 6. A history of body irradiation or organ transplantation. 2. Use of any of the following drugs/treatments or participation in a clinical study: 1. Prior treatment with CAR-T or other cellular therapy, or T-cell engager (TCE) therapy; 2. Anti-CD20 monoclonal antibody within 6 months prior to randomization; other B-cell or plasma cell-depleting therapy within 6-12 months prior to randomization; 3. Alkylating agent within 12 weeks prior to randomization; 4. Any biologic for MG treatment within 12 weeks prior to randomization; 5. Neonatal Fc receptor antagonist therapy within 8 weeks prior to randomization; 6. Janus kinase (JAK), Bruton tyrosine kinase (BTK), or tyrosine kinase 2 (TYK2) inhibitor within 12 weeks prior to randomization; 7. IVIg, subcutaneous immunoglobulin, or PLEX therapy within 4 weeks prior to randomization; 8. Live/attenuated live vaccine within 4 weeks prior to randomization, or planned vaccination during the study. 3. A history of malignancy within 5 years prior to screening; 4. Infection-related medical history and examinations: 1. A history of herpes zoster meeting any of the following: 1) A history of disseminated herpes zoster, herpes zoster encephalitis, or ocular herpes zoster involving the retina; 2) Recurrent herpes zoster with 2 or more episodes within 2 years; 3) Herpes zoster infection not fully resolved within 12 weeks prior to screening; 2. A history of tuberculosis (TB) or latent TB infection; 3. A known history of primary immunodeficiency, splenectomy, or any underlying condition predisposing to infection; 4. A history of recurrent infections requiring hospitalization and intravenous antibiotics; 5. Any infection requiring hospitalization and/or intravenous antimicrobial therapy within 8 weeks prior to randomization, or any infection requiring oral antimicrobial therapy within 2 weeks prior to randomization; 6. Positive test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody, treponemal pallidum antibody, or human immunodeficiency virus (HIV) antibody; for patients with HBsAg-negative but hepatitis B core antibody (HBcAb)-positive, regardless of the status of hepatitis B surface antibody (HBsAb), HBV-DNA testing is required to confirm their condition, with HBV-DNA-positive patients excluded and HBV-DNA-negative patients eligible to participate in the study. 5. General situation: 1. Pregnant or lactating females; 2. A history of alcohol abuse or illicit drug abuse within 1 year prior to screening; 3. A history of allergic diathesis, or known hypersensitivity/intolerance to any component of the investigational product; 4. Major surgery within 3 months prior to the screening, or planned major surgery during the study; 5. Any condition that, in the investigator's judgment, may affect evaluation of study drug safety and efficacy, or any other condition that renders the subject ineligible.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change from baseline in MG-ADL total score | at Week 24 |
Secondary
| Measure | Time frame |
|---|---|
| Change from baseline in Quantitative Myasthenia Gravis (QMG) score | at Week 24 |
| Change from baseline in Myasthenia Gravis Composite (MGC) total score | at Week 24 |
| Change from baseline in MG-ADL domain scores (ocular, bulbar, respiratory, limb) | at Week 24 |
| Change from baseline in QMG domain scores (ocular, bulbar, respiratory, limb) | at Week 24 |
| Proportion of participants with ≥3-point reduction from baseline in MG-ADL total score | at Week 24 |
| Proportion of participants with ≥50% reduction from baseline in MG-ADL total score | at Week 24 |
| Proportion of participants with ≥5-point reduction from baseline in QMG score | at Week 24 |
| Proportion of participants achieving Minimal Symptom Expression (MSE; MG-ADL total score 0 or 1) at Week 24 | at Week 24 |
| Change from baseline in Myasthenia Gravis Quality of Life 15-item revised (MG-QoL15r) total score | at Week 24 |
| Change from baseline in Neuro-QoL Fatigue subscale score | at Week 24 |
| Change from baseline in European Quality of Life 5-Dimensions 5-Levels (EQ-5D-5L) index score | at Week 24 |
| Proportion of participants without rescue therapy | through Week 24 |
| Incidence, severity grading, and drug-relatedness of adverse events (AEs) | through Week 24 |
| Incidence, severity grading, and drug-relatedness of serious adverse events (SAEs) | through Week 24 |
| Incidence, severity grading, and drug-relatedness of adverse events of special interest (AESIs) | through Week 24 |
| Change from baseline in C-SSRS | through Week 24 |
Countries
China
Contacts
CONTACTKunming Li
Outcome results
None listed