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

Study Overview
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Brief Summary
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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)

Official Title
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A Phase 3b, Multicenter, Open-Label, Single-Arm Study to Evaluate the Safety, Tolerability, and Efficacy of Zilucoplan in Participants With Generalized Myasthenia Gravis Switching From Intravenous Complement Component 5 Inhibitors to Subcutaneous Zilucoplan

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: zilucoplan (RA101495)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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 Participant has previously participated in this study or participant has previously been assigned to treatment in a study of the medication under investigation in this study Participant has participated in another study of an investigational study medication (and/or an investigational device) within the previous 30 days or is currently participating in another study of an investigational study medication (and/or an investigational device) Participant has known positive serology for muscle-specific kinase

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 0.3 mg/kg zilucoplan (RA101495)<br>Study participants will be treated with subcutaneous zilucoplan (0.3mg/kg/day) | Drug: zilucoplan (RA101495)<br>* Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment-emergent adverse events (TEAEs) over the Main Treatment Period | Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment. | From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) | 
| Incidence of treatment-emergent adverse events (TEAEs) leading to withdrawal of study medication over the Main Treatment Period | Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment. | From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline to Week 12 in MG ADL score | The Myasthenia Gravis-Activities of Daily Living (MG-ADL) profile provides an assessment of myasthenia gravis (MG) symptom severity and measures 8 items on a 0-3 scale, with 0 being the least severe. The total sum of the 8 items represents the MG-ADL score. The MG-ADL score can range from 0 (least severe) to 24 (most severe). | From Baseline to Week 12 | 
| Change from Baseline to Week 12 in the QMG score | The Quantitative Myasthenia Gravis (QMG) is a standardized and validated 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) | From Baseline to Week 12 | 
| Incidence of serious treatment-emergent adverse events (serious TEAEs) over the Main Treatment Period | Treatment-emergent serious adverse events (serious TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment and additionally are emergent untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Results in persistent disability/incapacity Is a congenital anomaly or birth defect Important medical events | From Baseline (Day 1) to Safety Follow-Up Visit of Main Treatment Period (up to Week 18) | 
| Incidence of study withdrawal over the Main Treatment Period | Incidence of study withdrawals based to pre-defined reasons in the Protocol. | From Baseline (Day 1) to End of Treatment Period (up to 12 weeks) | 

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