An Open-label Study to Evaluate the Safety, Tolerability, and Efficacy of Subcutaneous Zilucoplan in Participants With Generalized Myasthenia Gravis Who Were Previously Receiving Intravenous Complement Component 5 Inhibitors

NCT05514873 | Completed Phase 3 Results FDA Drug

• 1 other identifier: MG0017
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 12

Brief Summary

The purpose of the study is to evaluate the safety and tolerability of switching from intravenous (IV) complement component 5 (C5) inhibitors to subcutaneous (SC) Zilucoplan in study participants with generalized myasthenia gravis (gMG)

Conditions

Generalized Myasthenia Gravis

Keywords

gMG

Outcome Measures

Primary Outcomes (2)

• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) Over the Main Treatment Period

  An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of investigational medicinal product (IMP) and up to and including 40 days after the final dose (or last contact depending on which occurs first).

  From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)

• Percentage of Participants With TEAEs Leading to Withdrawal of Study Medication Over the Main Treatment Period

  An AE was any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication. A TEAE was defined as an AE starting on or after the time of first administration of IMP and up to and including 40 days after the final dose (or last contact depending on which occurs first).

  From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)

Secondary Outcomes (4)

• Change From Baseline to Week 12 in Myasthenia Gravis-Activities of Daily Living (MG-ADL) Score

  From Baseline to Week 12

• Change From Baseline to Week 12 in the Quantitative Myasthenia Gravis (QMG) Score

  From Baseline to Week 12

• Percentage of Participants With Serious TEAEs Over the Main Treatment Period

  From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)

• Percentage of Participants With Study Withdrawal Over the Main Treatment Period

  From Baseline (Day 1) to Safety Follow-Up Visit (40 days post last dose) of Main Treatment Period (up to approximately 19 weeks)

Study Arms (1)

0.3 mg/kg zilucoplan (RA101495)

EXPERIMENTAL

Study participants will be treated with subcutaneous zilucoplan (0.3mg/kg/day)

Drug: zilucoplan (RA101495)

Interventions

zilucoplan (RA101495) DRUG

Subcutaneous injection

0.3 mg/kg zilucoplan (RA101495)

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participant has been treated with an intravenous (IV) complement component 5 (C5) inhibitor approved for the treatment of generalized myasthenia gravis (gMG) at the recommended dose regimen for at least 3 months (for eculizumab) or 4 months (for ravulizumab) prior to Screening with a clinically stable disease as per the Investigator's judgment.
• Participant is willing to switch from his/her current IV C5 inhibitor to subcutaneous (SC) zilucoplan (ZLP)
• Participant has a documented diagnosis of gMG (Myasthenia Gravis Foundation of America; MGFA Class II-IVa) at Screening based on participant history and supported by previous evaluations
• Participant has a well-documented record of positive serology for acetylcholine receptor binding autoantibodies prior to Screening
• Participant has no more than a 2-point change in Myasthenia Gravis-Activities of Daily Living (MG-ADL) score at Baseline compared with the Screening Visit
• Participant has had no change in corticosteroid dose during the Screening Period and no change in corticosteroid dose is anticipated to occur during the 12-week Main Treatment Period
• Participant has had no change in immunosuppressive therapy, including dose, during the Screening Period and no change in immunosuppressive therapy is anticipated to occur during the 12-week Main Treatment Period
• Participant has a record of vaccination with at least 1 dose of a quadrivalent meningococcal vaccine and meningococcal serotype B vaccine at least 14 days prior to the first dose of ZLP if not vaccinated within 3 years prior to the start of study medication
• Male and/or female
• A male participant is recommended to agree to use contraception during the study and for at least 40 days (5 half lives) after the last dose of study medication, and refrain from donating sperm during this period.
• A female participant is eligible to participate if she is not pregnant; not breastfeeding, and at least one of the following conditions applies:
• Not a woman of childbearing potential (WOCBP) OR
• A WOCBP who agrees to follow the contraceptive guidance during the study and for at least 40 days (5 half lives) after the last dose of study medication.
• Participant is capable of giving signed informed consent

You may not qualify if:

• Participant has any medical or psychiatric condition that, in the opinion of the Investigator, could jeopardize or would compromise the participant's ability to participate in this study
• Participant has a known hypersensitivity to any components of the study medication as stated in this protocol
• Participant has had a thymectomy within 6 months prior to Baseline or has one scheduled to occur during the 12-week Main Treatment Period
• Participant has a history of meningococcal disease
• Participant has or has had a current or recent systemic infection within 2 weeks prior to Baseline or an infection requiring IV antibiotics within 4 weeks prior to Baseline
• Participant has active malignancy (except curatively resected squamous or basal cell carcinoma of the skin) requiring surgery, chemotherapy, or radiation within the prior 12 months (participants with a history of malignancy who have undergone curative resection or otherwise not requiring treatment for at least 12 months prior to Screening with no detectable recurrence are allowed).
• Participant has a lifetime history of suicide attempt (including an actual attempt, interrupted attempt, or aborted attempt), or has had suicidal ideation with at least some intent to act in the past 6 months as indicated by a positive response ("Yes") to either question 4 or question 5 of the "Screening/Baseline" version of the C-SSRS at Screening.
• Participant has alanine transaminase (ALT), aspartate aminotransferase (AST), or alkaline phosphatase (ALP) \>2.5x upper limit of normal (ULN)
• Participant has bilirubin \>1.5xULN (isolated bilirubin \>1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin \<35%).
• Participant has current unstable liver or biliary disease per Investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
• QTc interval \>450msec for male participants, QTc \>470msec for female participants, or QTc \>480 msec in participants with bundle branch block
• Participant has had recent surgery requiring general anesthesia within 2 weeks prior to Screening or is expected to have surgery requiring general anesthesia during the 12-week Main Treatment Period
• Participant has received a treatment with an experimental drug within 30 days or 5 half lives of the experimental drug (whichever is longer) prior to Baseline
• Participant has received treatment with rituximab within 6 months prior to Baseline or treatment is planned to occur during the study
• Participant has received treatment with intravenous immunoglobulin G (IVIG), SC immunoglobulin, or plasma exchange PLEX 4 weeks prior to Baseline or participant is on chronic IVIG, SC immunoglobulin, or PLEX

Sponsors & Collaborators

• UCB Biopharma SRL: lead

Study Sites (12)

Mg0017 50564

Scottsdale, Arizona, 85251, United States

Location

Mg0017 50559

Los Angeles, California, 90095, United States

Location

Mg0017 50593

Rancho Mirage, California, 92270, United States

Location

Mg0017 50099

San Francisco, California, 94143, United States

Location

Mg0017 50557

O'Fallon, Illinois, 62269, United States

Location

Mg0017 50556

Chapel Hill, North Carolina, 27599, United States

Location

Mg0017 50086

Charlotte, North Carolina, 28207, United States

Location

Mg0017 50076

Columbus, Ohio, 43221, United States

Location

Mg0017 50555

Austin, Texas, 78759, United States

Location

Mg0017 50304

Dallas, Texas, 75390-8866, United States

Location

Mg0017 50111

Seattle, Washington, 98195-0001, United States

Location

Mg0017 50569

Greenfield, Wisconsin, 53228, United States

Location

Related Publications (1)

• Freimer M, Desai U, Govindarajan R, Kang MK, Khan S, Khatri B, Levine T, Macwan S, Shieh PB, Weiss MD, Bloemers J, Boroojerdi B, Delicha EM, Lavrov A, Singh P, Howard JF Jr. Switching to subcutaneous zilucoplan from intravenous complement component 5 inhibitors in generalised myasthenia gravis: a phase IIIb, open-label study. Ther Adv Neurol Disord. 2025 Jul 5;18:17562864251347283. doi: 10.1177/17562864251347283. eCollection 2025.

  PMID: 40620733 RESULT

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

Results Point of Contact

• Title: UCB
• Organization: Cares

UCBCares@ucb.com

001 844 599 2273

Study Officials

• UCB Cares

  001 844 599 2273

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 22, 2022
• First Posted: August 25, 2022
• Study Start: October 31, 2022
• Primary Completion: March 13, 2024
• Study Completion: October 23, 2024
• Last Updated: September 3, 2025
• Results First Posted: March 30, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Data from this trial may be requested by qualified researchers six months after product approval in the US and/or Europe or global development is discontinued, and 18 months after trial completion.
• Access Criteria: Qualified researchers may request access to anonymized IPD and redacted study documents which may include: raw datasets, analysis-ready datasets, study protocol, blank case report form, annotated case report form, statistical analysis plan, dataset specifications, and clinical study report. Prior to use of the data, proposals need to be approved by an independent review panel at www.Vivli.org and a signed data sharing agreement will need to be executed.All documents are available in English only, for a pre-specified time, typically 12 months, on a password protected portal.

Locations

US (12)