This is an open-label, multicenter, interventional phase 3b study in participants with AChR+ gMG and severe exacerbation that require hospitalization. Patients will receive subcutaneous zilucoplan injections daily for 12 weeks. Participation in the study will last for approximately 18 weeks.

The primary objective of the study is to evaluate the efficacy of subcutaneous zilucoplan in participants with AChR antibody positive gMG who experience severe exacerbations requiring hospitalization. A total of 15 patients will be enrolled in the study with treatment lasting 12 weeks. Dosing will be weight based.

Patients will be presented with the option of undergoing standard of care plasma exchange or IVIG or to participate in the research study to determine if the use of zilucoplan would rapidly alleviate the most severe symptoms of gMG (respiratory dysfunction and/or bulbar dysfunction). Assessments will include medical history, physical exam, vital signs and bloodwork. MG assessments will also be conducted including the QMG and MG-ADL and patient reported outcome measures like the Myasthenia Gravis Quality of Life 15 item Revised (MGQoL15r) scale. Treatment will start in the hospital and once the patient is discharged, treatment will continue as an outpatient. Current medications and adverse events will also be reviewed and documented. Patients who undergo treatment with zilucoplan will be vaccinated against meningitis prior to starting the study drug and will continue with the recommended set of vaccines for 6 months. Antibiotics will be taken concurrently until patients are fully vaccinated.

The study aims to find a less invasive method to treat MG patients who are experiencing an exacerbation. Utilization of a subcutaneous medication with relatively rapid onset of action may provide a viable alternative to the current therapeutic approaches. If rapid complement inhibition were to prove efficacious in the treatment of acute exacerbations of gMG, this therapy would potentially obviate the need for transfer to tertiary care centers, avoid the potentially hazardous placement of a large bore central venous catheter for plasmapheresis, and potentially reduce hospital length of stay.

Inclusion Criteria:

• Patient determined to have severe MG exacerbation (e.g. bulbar and/or respiratory symptoms requiring hospitalization, neck extension weakness)
• MGFA class II - IVb
• Male or female aged ≥18
• MG-ADL ≥6 in non-ocular domains
• Serology - AChR antibody positive (or historically available data)
• If female of child-bearing potential (i.e., not surgically sterile or post-menopausal defined as age > 51 years without menses for ≥ 2 years), negative serum pregnancy test at screening
• Women of child-bearing potential or men with sexual partners of childbearing potential must be willing to use an acceptable method of birth control for the duration of the study and for 40 days after the last dose of study drug therapy. Acceptable methods of birth control include abstinence, oral contraceptives, the contraceptive patch, intra-uterine device, the contraceptive ring, and or barrier contraception such as condoms with spermicide.
• Completed or updated meningococcal vaccination or initiated meningococcal vaccination with appropriate antibiotic prophylaxis according to current USPI and ACIP guidelines

Exclusion Criteria:

• History of meningococcal disease
• Participants requiring intubation prior to study start.
• Recent significant infections which could have caused exacerbation e.g. sepsis and wound infections
• Pregnancy or lactating
• Recent surgery (<4 weeks). Minor procedures/surgeries allowed at the discretion of the site principal investigator
• Current use or known failure of C5 inhibitors in the previous 3 months
• Initiation of plasma exchange or IVIG in the past 4 weeks
• Participation in concurrent clinical trial with a therapeutic medication
• Rituximab use in the previous 9 months
• Any clinically significant condition or illness, which, in the opinion of the PI, would pose a risk to the subject or might confound the study