A Study to Evaluate Subcutaneous Zilucoplan in Pediatric Participants With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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The purpose of this study is to assess the pharmacokinetics, pharmacodynamics, safety, tolerability, immunogenicity and activity of zilucoplan (ZLP) in pediatric study participants with generalized myasthenia gravis (gMG).

Official Title
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A Multicenter Open-Label, Uncontrolled Study to Evaluate the Pharmacokinetics, Pharmacodynamics, Safety, Tolerability, and Activity of Zilucoplan in Pediatric Study Participants From 2 to Less Than 18 Years of Age With Acetylcholine Receptor Antibody Positive Generalized Myasthenia Gravis

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: Zilucoplan


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: United States of America (USA) specific inclusion criterion: - Participant must be 12 to <18 years of age at the time of signing the Informed consent/assent according to local regulation Rest of world (ROW) specific inclusion criterion: - Participant must be 2 to <18 years of age at the time of signing the Informed consent/assent according to local regulation Global inclusion criteria: Participant has a diagnosis of generalized myasthenia gravis (gMG) confirmed by a prior positive serologic test result to acetylcholine receptor (AChR) prior to Screening Participant meets the criteria as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification II to IV at Screening Participants with gMG, including: An MG-activities of daily living (MG-ADL) total score of 6 or more in adolescents from 12 years to <18 years of age at Screening Documented weakness in at least 1 limb, neck, or bulbar muscle in children from 2 years to <12 years of age at Screening (does not apply to US) Documented vaccination against meningococcal infections within 3 years prior to study start. If not fully vaccinated, participants must receive appropriate prophylactic antibiotic treatment until at least 2 weeks after the initial dose of vaccine(s) Exclusion Criteria: Participant has known positive serology for muscle-specific kinase 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 had a thymectomy within 6 months prior to Baseline Participant has minimal Manifestation Status of MG based on the clinical judgement of the Investigator Current or recent systemic infection within 2 weeks prior to Baseline or infection requiring intravenous antibiotics within 4 weeks prior to Baseline

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 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: Zilucoplan Arm<br>Study participants will receive zilucoplan in pre-defined dose based on their weight. | Drug: Zilucoplan<br>* Zilucoplan will be administered subcutaneously to pediatric study participants.<br>* Other names: RA101495;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma concentrations of zilucoplan (ZLP) sampled at Week 4 (Day 29) | Blood samples will be collected for measurement of plasma concentrations of ZLP on Day 29 predose. | Week 4 (Day 29) | 
| Change from Baseline in sheep red blood cell (sRBC) lysis at Week 4 (Day 29) | Samples for measurement of sRBC lysis will be collected on Day 29 predose. | Week 4 (Day 29) | 
| Change from Baseline in complement component 5 (C5) levels at Week 4 (Day 29) | Samples for measurement of C5 will be collected on Day 29 predose. | Week 4 (Day 29) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of treatment-emergent adverse events (TEAEs) during the course of the study | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal (investigational) product, whether or not related to the medicinal (investigational) product. | From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) | 
| Occurrence of treatment-emergent serious adverse events (TESAEs) | A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death Is life-threatening Requires inpatient hospitalization or prolongation of existing hospitalization Results in persistent disability/incapacity Is a congenital anomaly/birth defect Important medical events | From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) | 
| Occurrence of TEAEs leading to permanent withdrawal of investigational medicinal product (IMP) | An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. AEs leading to permanent withdrawal of study medication. | From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) | 
| Occurrence of treatment-emergent infections | Percentage of participants who experienced treatment-emergent infections as adverse events. An adverse event (AE) is any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. | From Baseline (Day 1) to Safety-Follow-Up Visit (up to Week 15) | 
| Occurrence of antidrug antibody (ADA) and anti- polyethylene glycol (PEG) antibodies at Week 4 (Day 29) | ADA and anti-PEG antibodies will be evaluated in serum samples. | Week 4 (Day 29) | 
| Change in MG-activities of daily living (MG-ADL) score from Baseline to Week 4 (Day 29). | The MG-ADL score is an 8-item patient-reported outcome (PRO) instrument. The MG-ADL targets symptoms and disability across ocular, bulbar, respiratory, and axial symptoms. The item responses are scored from 0 to 3, and the total score of MG-ADL is the sum of the 8 items and ranges from 0 to 24, with a higher score indicating more disability. | Week 4 (Day 29) | 
| Change in Quantitative MG (QMG) score from Baseline to Week 4 (Day 29) | QMG score is a standardized and validated quantitative strength scoring system that was developed specifically for MG. The QMG total score is obtained by summing the responses to each individual item (13 items; Responses: None=0, Mild=1, Moderate=2, Severe=3). The score ranges from 0 to 39, with lower scores indicating lower disease activity. | Week 4 (Day 29) | 
| Myasthenia Gravis Foundation of America Post-Interventional Status (MGFA-PIS) at Week 4 (Day 29) | The MGFA-PIS is a physician-determined assessment of clinical symptoms of MG after initiation of MG specific therapy. For the purpose of the current study, Minimal Manifestation will be determined at each scheduled time point after treatment initiation (rather than after 1 year). Change in status (improved, unchanged, worse, exacerbation, or died of MG) will also be determined. | Week 4 (Day 29) | 
| Change in Pediatric Quality of Life Inventory (PedsQoL), Version 4 domain scores from Baseline to Week 4 (Day 29) | The PedsQoL generic core scale (Version 4) is a validated instrument that is suitable for use with pediatric populations. PedsQoL generic core scales assess Physical Functioning, Emotional Functioning, Social Functioning, and School Functioning. The scale has 23 items with a score range of 0 to 4. Following transformation, the score range of each domain as well as the total score is 0-100 with higher scores indicating higher HRQoL. | Week 4 (Day 29) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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RA101495, gMG, generalized myasthenia gravis, zilucoplan, pediatric, MG0014