Zilucoplan for Severe gMG Exacerbations

NCT07215949 | Recruiting Phase 3 FDA Drug

• 1 other identifier: MG0036-OSU
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Generalized Myasthenia Gravis (gMG)

Keywords

MG; exacerbation; zilucoplan

Outcome Measures

Primary Outcomes (1)

• Change from baseline to Week 2 in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) score

  The MG-ADL is an assessment that measures MG symptom severity. There are 8 items measured on a scale of 0-3 with 0 being the least severe. The total of the 8 items represents the MG-ADL score. The score can range from 0 (least severe) to 24 (most severe).

  From baseline to Week 2

Secondary Outcomes (1)

• Change from baseline to week 12 in Myasthenia Gravis - Activities of Daily Living (MG-ADL) score

  From baseline to week 12

Study Arms (1)

Zilucoplan

EXPERIMENTAL

Subcutaneous zilucoplan

Drug: Zilucoplan®

Interventions

Zilucoplan® DRUG

Subcutaneous injections of zilucoplan will be administered daily. The dose is dependent on the body weight of the patient. Each patient will receive a kit with prefilled syringes.

Zilucoplan

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Miriam Freimer: lead
• UCB Pharma: collaborator

Study Sites (1)

The Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (12)

• Vu T, Meisel A, Mantegazza R, Annane D, Katsuno M, Aguzzi R, Enayetallah A, Beasley KN, Rampal N, Howard JF. Terminal Complement Inhibitor Ravulizumab in Generalized Myasthenia Gravis. NEJM Evid. 2022 May;1(5):EVIDoa2100066. doi: 10.1056/EVIDoa2100066. Epub 2022 Apr 26.

  PMID: 38319212 BACKGROUND

• Howard JF Jr, Bresch S, Genge A, Hewamadduma C, Hinton J, Hussain Y, Juntas-Morales R, Kaminski HJ, Maniaol A, Mantegazza R, Masuda M, Sivakumar K, Smilowski M, Utsugisawa K, Vu T, Weiss MD, Zajda M, Boroojerdi B, Brock M, de la Borderie G, Duda PW, Lowcock R, Vanderkelen M, Leite MI; RAISE Study Team. Safety and efficacy of zilucoplan in patients with generalised myasthenia gravis (RAISE): a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Neurol. 2023 May;22(5):395-406. doi: 10.1016/S1474-4422(23)00080-7.

  PMID: 37059508 BACKGROUND

• Kusner LL, Kaminski HJ. The role of complement in experimental autoimmune myasthenia gravis. Ann N Y Acad Sci. 2012 Dec;1274(1):127-32. doi: 10.1111/j.1749-6632.2012.06783.x.

  PMID: 23252907 BACKGROUND

• Kapoor M, Spillane J, Englezou C, Sarri-Gonzalez S, Bell R, Rossor A, Manji H, Reilly MM, Lunn MP, Carr A. Thromboembolic risk with IVIg: Incidence and risk factors in patients with inflammatory neuropathy. Neurology. 2020 Feb 11;94(6):e635-e638. doi: 10.1212/WNL.0000000000008742. Epub 2019 Dec 18.

  PMID: 31852814 BACKGROUND

• Mandawat A, Kaminski HJ, Cutter G, Katirji B, Alshekhlee A. Comparative analysis of therapeutic options used for myasthenia gravis. Ann Neurol. 2010 Dec;68(6):797-805. doi: 10.1002/ana.22139.

  PMID: 21061395 BACKGROUND

• Chang CC, Yeh JH, Chiu HC, Liu TC, Chen YM, Jhou MJ, Lu CJ. Assessing the length of hospital stay for patients with myasthenia gravis based on the data mining MARS approach. Front Neurol. 2023 Dec 14;14:1283214. doi: 10.3389/fneur.2023.1283214. eCollection 2023.

  PMID: 38156090 BACKGROUND

• Sanders DB, Wolfe GI, Benatar M, Evoli A, Gilhus NE, Illa I, Kuntz N, Massey JM, Melms A, Murai H, Nicolle M, Palace J, Richman DP, Verschuuren J, Narayanaswami P. International consensus guidance for management of myasthenia gravis: Executive summary. Neurology. 2016 Jul 26;87(4):419-25. doi: 10.1212/WNL.0000000000002790. Epub 2016 Jun 29.

  PMID: 27358333 BACKGROUND

• Wolfe GI, Kaminski HJ, Aban IB, Minisman G, Kuo HC, Marx A, Strobel P, Mazia C, Oger J, Cea JG, Heckmann JM, Evoli A, Nix W, Ciafaloni E, Antonini G, Witoonpanich R, King JO, Beydoun SR, Chalk CH, Barboi AC, Amato AA, Shaibani AI, Katirji B, Lecky BR, Buckley C, Vincent A, Dias-Tosta E, Yoshikawa H, Waddington-Cruz M, Pulley MT, Rivner MH, Kostera-Pruszczyk A, Pascuzzi RM, Jackson CE, Garcia Ramos GS, Verschuuren JJ, Massey JM, Kissel JT, Werneck LC, Benatar M, Barohn RJ, Tandan R, Mozaffar T, Conwit R, Odenkirchen J, Sonett JR, Jaretzki A 3rd, Newsom-Davis J, Cutter GR; MGTX Study Group. Randomized Trial of Thymectomy in Myasthenia Gravis. N Engl J Med. 2016 Aug 11;375(6):511-22. doi: 10.1056/NEJMoa1602489.

  PMID: 27509100 BACKGROUND

• Ramizuddin MK. Review on: Myasthenia gravis and telithromycin-myasthenia crisis. IOSR J Dent Med Sci. 2014;13(7):67-97.

  BACKGROUND

• Gilhus NE. Myasthenia Gravis. N Engl J Med. 2016 Dec 29;375(26):2570-2581. doi: 10.1056/NEJMra1602678. No abstract available.

  PMID: 28029925 BACKGROUND

• Howard JF Jr, Utsugisawa K, Benatar M, Murai H, Barohn RJ, Illa I, Jacob S, Vissing J, Burns TM, Kissel JT, Muppidi S, Nowak RJ, O'Brien F, Wang JJ, Mantegazza R; REGAIN Study Group. Safety and efficacy of eculizumab in anti-acetylcholine receptor antibody-positive refractory generalised myasthenia gravis (REGAIN): a phase 3, randomised, double-blind, placebo-controlled, multicentre study. Lancet Neurol. 2017 Dec;16(12):976-986. doi: 10.1016/S1474-4422(17)30369-1. Epub 2017 Oct 20.

  PMID: 29066163 BACKGROUND

• Rodrigues E, Umeh E, Aishwarya, Navaratnarajah N, Cole A, Moy K. Incidence and prevalence of myasthenia gravis in the United States: A claims-based analysis. Muscle Nerve. 2024 Feb;69(2):166-171. doi: 10.1002/mus.28006. Epub 2023 Dec 1.

  PMID: 38040629 BACKGROUND

Related Links

• Zilbrysq Package Insert
• Advisory Committee on Immunization Practices (ACIP) Vaccine Recommendations

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

zilucoplan

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Miriam Freimer, MD

  Ohio State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Julie Agriesti, MACPR, CCRC

CONTACT

614-293-4098; Julie.Agriesti@osumc.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Neurology

Study Record Dates

• First Submitted: October 6, 2025
• First Posted: October 14, 2025
• Study Start: January 20, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)