A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG)

• Sponsor: Alexion Pharmaceuticals (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT03759366
• Collaborator: (none)
• Enrollment: 11
• Locations: 16
• Arm: 1
• Anticipated Duration (Months): 79.3
• Patients Per Site: 0.7
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of eculizumab in the treatment of pediatric refractory gMG based on change from Baseline in the Quantitative Myasthenia Gravis (QMG) score for disease severity.

Condition or Disease	Intervention/Treatment	Phase
Myasthenia Gravis; Myasthenia Gravis, Juvenile Form; Myasthenia Gravis, Generalized	Drug: Eculizumab	Phase 3

Detailed Description

The study will consist of an up to 4-week Screening Period, 26-week Primary Evaluation Treatment Period, an additional (up to) to 208-week Extension Period, and an 8-week Safety Follow-up Period.

Study Design

• Study Type: Interventional
• Actual Enrollment: 11 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Eculizumab in Pediatric Patients With Refractory Generalized Myasthenia Gravis
• Actual Study Start Date: Dec 21, 2018
• Actual Primary Completion Date: Jan 6, 2022
• Anticipated Study Completion Date: Jul 31, 2025

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Eculizumab Intravenous (IV) Infusion In the Primary Evaluation Treatment Period (26 weeks), eculizumab will be administered weekly during the initial induction phase and every 2 weeks during the maintenance phase. In the Extension Period (up to 208 weeks), participants will continue to receive eculizumab every 2 weeks. Eculizumab will be administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight.

Drug: Eculizumab; Eculizumab will be administered by IV infusion.

Outcome Measures

Primary Outcome Measures

1. Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment [Baseline, Week 26]

   The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.

Secondary Outcome Measures

1. Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment [Baseline, Week 26]

   The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with myasthenia gravis (MG). The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.

2. Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment [Week 26]

   The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.

3. Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment [Week 26]

   The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.

4. Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment [Week 26]

   The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.

5. Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment [Week 26]

   The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.

6. Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment [Baseline, Week 26]

   The MGC is a validated assessment tool for measuring clinical status of participants with MG. The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross motor (2 items). The scales are weighted for clinical significance that incorporates patient-reported outcomes. The MGC total score ranges from 0 to 50, with lower scores indicating less functional impairment and higher scores indicating greater functional impairment.

7. Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Scale Score at Week 26 Regardless of Rescue Treatment [Baseline, Week 26]

   The EQ-5D-Y is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each of which is completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participant <12 years of age. Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme problems). The EQ visual analogue scale (VAS) records the participant's self-rated health on a vertical, 20 cm VAS where the endpoints are labelled 'Best imaginable health state, marked as 100' and 'Worst imaginable health state, marked as 0'.

8. Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment [Baseline, Week 26]

   The Neuro-QoL Pediatric Fatigue questionnaire is a reliable and validated brief 11-item survey of fatigue, completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participants <12 years of age. Each item was scored on a scale of 1 to 5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Total score is the sum of each item's score and it ranges from 11 to 55. Higher scores indicate greater fatigue and greater impact of MG on activities.

9. Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26 [Week 26]

   The MG clinical state (improved, unchanged, and worse) was assessed using the MGFAPIS.

10. Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use [Baseline up to Week 26]

    Rescue therapy (for example, high dose corticosteroid, plasma exchange [PE], or intravenous immunoglobulin [IVIg]) was to be allowed when a participant experienced clinical deterioration. Clinical deterioration was defined as follows: Participants who experienced an MG crisis, which was defined as weakness due to MG that was severe enough to necessitate intubation or to delay extubation following surgery; or, Significant symptomatic worsening that required rescue medication in the opinion of the Investigator; or, Participants for whom the Investigator believed that the participants' health was in jeopardy if rescue therapy was not given.

11. Pharmacokinetics (PK): Serum Concentration Of Eculizumab [24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26]

12. Pharmacodynamics (PD): Serum Free Complement Component 5 (C5) Concentrations [Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26]

13. PD: Percentage of Hemolysis (In Vitro Assay) [Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years to 17 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Male or female pediatric participants 6 to <18 years of age at time of assent/consent.

• Vaccinated against Neisseria meningitidis.

• Documented vaccination against Haemophilus influenzae and Streptococcus pneumoniae infections prior to dosing as per local and country specific immunization guidelines for the appropriate age group.

• Diagnosis of MG confirmed by positive serologic test for anti-acetylcholine receptor antibodies at Screening, and 1 of the following: (a) history of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography or repetitive nerve stimulation; (b) history of positive anticholinesterase test (for example, edrophonium chloride or neostigmine test); or (c) participant demonstrated improvement in MG signs on oral acetylcholinesterase inhibitors, as assessed by the Investigator.

• Presence of refractory gMG, defined as participants with gMG who have 1 or more of the following: (a) failed treatment ≥1 year with at least 1 immunosuppressive therapies (IST), defined as follows: (1) persistent weakness with impairment of activities of daily living; (2) myasthenia gravis (MG) exacerbation and/or crisis while on treatment; or (3) intolerance to ISTs due to side effect or comorbid condition(s). (b) Require maintenance plasma exchange (PE) or intravenous immunoglobulin (IVIg) to control symptoms; and/or (c) in the opinion of the Investigator, MG poses a significant functional burden despite current MG treatment.

• MGFA Clinical Classification of Class II to IV at Screening.

• In patients aged 12 to 18 years, QMG total score ≥ 12 at Screening; in patients aged 6 to 11 years, no minimum QMG is required for inclusion; however, patients must have documented limb weakness in at least one limb.

• All MG-specific treatment has been administered at a stable dosing regimen of adequate duration prior to Screening.

Exclusion Criteria:

• Parent or legal guardian is an Alexion employee.

• Any active or untreated thymoma. History of thymic carcinoma or thymic malignancy unless deemed cured by adequate treatment with no evidence of recurrence for ≥5 years before Screening.

• History of thymectomy within 12 months prior to Screening.

• Are pregnant or lactating.

• Any unresolved acute, or chronic, systemic bacterial or other infection, which is clinically significant in the opinion of the Investigator and has not been treated with appropriate antibiotics.

• Use of PE within 4 weeks prior to first dose.

• Use of rituximab within 6 months prior to first dose.

• Patients who are under 15 kg and are receiving maintenance IVIg.

• Participation in another interventional treatment study or use of any experimental therapy within 30 days before initiation of study drug on Day 1 in this study or within 5 half-lives of that investigational product, whichever is greater.

• Have previously received treatment with eculizumab or other complement inhibitors.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Trial Site	Los Angeles	California	United States	90027
2	Clinical Trial Site	Tampa	Florida	United States	33612
3	Clinical Trial Site	Chicago	Illinois	United States	60611
4	Clinical Trial Site	Columbia	Missouri	United States	65211
5	Clinical Trial Site	Saint Louis	Missouri	United States	63104
6	Clinical Trial Site	Chapel Hill	North Carolina	United States	27599-1651
7	Clinical Trial Site	Akron	Ohio	United States	44308
8	Clinical Trial Site	Philadelphia	Pennsylvania	United States	19104
9	Clinical Trial Site	Charleston	South Carolina	United States	29425-8572
10	Clinical Trial Site	Chiba-shi	Chiba-Ken	Japan	260-8677
11	Clinical Trial Site	Saitama	Iruma-gun	Japan	350-0495
12	Clinical Trial Site	Tokyo	Itabasha-ku	Japan	173-0003
13	Clinical Trial Site	Tokyo	Shinjuku-ku	Japan	162-8666
14	Clinical Trial Site	Mibu	Tochigi	Japan	3210293
15	Clinical Trial Site	Amsterdam		Netherlands	1105
16	Clinical Trial Site	Leiden		Netherlands	2333

Sponsors and Collaborators

• Alexion Pharmaceuticals

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol - Sep 28, 2020
• Statistical Analysis Plan - Oct 30, 2019

More Information

Publications

None provided.

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03759366
• Other Study ID Numbers: ECU-MG-303
• First Posted: Nov 30, 2018
• Last Update Posted: Aug 25, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Alexion Pharmaceuticals: Myasthenia Gravis; Myasthenia Gravis, Generalized
• Additional relevant MeSH terms: Myasthenia Gravis; Muscle Weakness; Eculizumab

Study Results

Participant Flow

Recruitment Details	The study included a Primary Evaluation Treatment Period of 26 weeks, an Extension Period of up to an additional 208 weeks, and a Follow-up Period of 8 weeks. All participants were offered participation in the Extension Period of the study.
Pre-assignment Detail	Interim results at data cut-off date 06 January 2022 has been reported. Final results will be posted after study completion.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by intravenous (IV) infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 milligrams (mg), based on the participant's current body weight.
Period Title: Primary Evaluation Period (26 Weeks)
STARTED	11
COMPLETED	10
NOT COMPLETED	1
Period Title: Primary Evaluation Period (26 Weeks)
STARTED	10
COMPLETED	0
NOT COMPLETED	10

Baseline Characteristics

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Overall Participants	11
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	14.8 (1.78)
Sex: Female, Male (Count of Participants)
Female	9 81.8%
Male	2 18.2%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 18.2%
Not Hispanic or Latino	9 81.8%
Unknown or Not Reported	0 0%
Race/Ethnicity, Customized (Count of Participants)
Asian	3 27.3%
Black or African American	5 45.5%
White	2 18.2%
Other	1 9.1%
QMG Total Score (units on a scale) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [units on a scale]	16.7 (5.64)

Outcome Measures

1. Primary Outcome

Title	Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment
Description	The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

Modified full analysis set (mFAS) included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-6.1 (4.56)

2. Secondary Outcome

Title	Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment
Description	The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with myasthenia gravis (MG). The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-2.5 (1.78)

3. Secondary Outcome

Title	Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment
Description	The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	50.0 (18.7) 454.5%

4. Secondary Outcome

Title	Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment
Description	The MG-ADL is an 8-point questionnaire that focuses on relevant symptoms and functional performance of activities of daily living in participants with MG. The 8 items of the MG-ADL are derived from symptom-based components of the original 13-item QMG to assess disability secondary to ocular (2 items), bulbar (3 items), respiratory (1 item), and gross motor or limb (2 items) impairment related to effects from MG. In this functional status instrument, each response is graded from 0 (normal) to 3 (most severe). The range of total MG-ADL score is 0 to 24, with higher score indicating more severe disease.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	50.0 (18.7) 454.5%

5. Secondary Outcome

Title	Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment
Description	The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70.0 (34.8) 636.4%

6. Secondary Outcome

Title	Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment
Description	The QMG scoring system consists of 13 items: ocular (2 items), facial (1 item), bulbar (2 items), gross motor (6 items), axial (1 item), and respiratory (1 item). Each item is graded from 0 to 3, (0 = none, 1 = mild, 2 = moderate, and 3 = severe). The range of total QMG score is 0 to 39, with higher score indicating more severe disease.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Number (95% Confidence Interval) [percentage of participants]	70.0 (34.8) 636.4%

7. Secondary Outcome

Title	Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment
Description	The MGC is a validated assessment tool for measuring clinical status of participants with MG. The MGC assesses 10 important functional areas most frequently affected by MG: ocular (2 items), facial (1 item), bulbar (3 items), respiratory (1 item), axial (1 item), and gross motor (2 items). The scales are weighted for clinical significance that incorporates patient-reported outcomes. The MGC total score ranges from 0 to 50, with lower scores indicating less functional impairment and higher scores indicating greater functional impairment.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	9
Mean (Standard Deviation) [units on a scale]	-9.6 (6.25)

8. Secondary Outcome

Title	Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Scale Score at Week 26 Regardless of Rescue Treatment
Description	The EQ-5D-Y is a reliable and validated survey of health status in 5 areas: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression, each of which is completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participant <12 years of age. Each area has 3 levels: Level 1 (no problems), Level 2 (some problems), and Level 3 (extreme problems). The EQ visual analogue scale (VAS) records the participant's self-rated health on a vertical, 20 cm VAS where the endpoints are labelled 'Best imaginable health state, marked as 100' and 'Worst imaginable health state, marked as 0'.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	23.5 (23.34)

9. Secondary Outcome

Title	Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment
Description	The Neuro-QoL Pediatric Fatigue questionnaire is a reliable and validated brief 11-item survey of fatigue, completed by the participant for participants ≥12 years of age (at time of assessment) and completed by the participant's caregiver or with caregiver assistance for participants <12 years of age. Each item was scored on a scale of 1 to 5 (1=Not at all, 2=A little bit, 3=Somewhat, 4=Quite a bit, 5=Very much). Total score is the sum of each item's score and it ranges from 11 to 55. Higher scores indicate greater fatigue and greater impact of MG on activities.
Time Frame	Baseline, Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Mean (Standard Deviation) [units on a scale]	-7.9 (7.37)

10. Secondary Outcome

Title	Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26
Description	The MG clinical state (improved, unchanged, and worse) was assessed using the MGFAPIS.
Time Frame	Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab. Overall number of participants analyzed = participants evaluable for this outcome measure.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Improved	10 90.9%
Unchanged	0 0%
Worse	0 0%

11. Secondary Outcome

Title	Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use
Description	Rescue therapy (for example, high dose corticosteroid, plasma exchange [PE], or intravenous immunoglobulin [IVIg]) was to be allowed when a participant experienced clinical deterioration. Clinical deterioration was defined as follows: Participants who experienced an MG crisis, which was defined as weakness due to MG that was severe enough to necessitate intubation or to delay extubation following surgery; or, Significant symptomatic worsening that required rescue medication in the opinion of the Investigator; or, Participants for whom the Investigator believed that the participants' health was in jeopardy if rescue therapy was not given.
Time Frame	Baseline up to Week 26

Outcome Measure Data

Analysis Population Description

mFAS included participants 12 to <18 years of age who received at least 1 dose of eculizumab.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	11
Clinical Deterioration	9.1 82.7%
MG Crisis	9.1 82.7%
Requiring Rescue Therapy	9.1 82.7%

12. Secondary Outcome

Title	Pharmacokinetics (PK): Serum Concentration Of Eculizumab
Time Frame	24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26

Outcome Measure Data

Analysis Population Description

PK analysis set included participants who had PK data assessments during this study. Here, number analyzed = participants evaluable at specified timepoint.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	11
Day 1, 24 hours postdose (n = 11)	359.6 (105.18)
Week 12, Predose	382.8 (159.57)
Week 12, 60 minutes postdose	910.5 (277.29)
Week 26, Predose	433.9 (171.85)

13. Secondary Outcome

Title	Pharmacodynamics (PD): Serum Free Complement Component 5 (C5) Concentrations
Time Frame	Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26

Outcome Measure Data

Analysis Population Description

PD analysis set included participants who had PD data assessments during this study. Here, number analyzed = participants evaluable at specified timepoint.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	11
Baseline	172.7 (34.52)
Day 1, 24 hours postdose	0.0 (0.01)
Week 12, Predose	0.0 (0.01)
Week 12, 60 minutes postdose	0.0 (0.01)
Week 26, Predose	0.0 (0.02)

14. Secondary Outcome

Title	PD: Percentage of Hemolysis (In Vitro Assay)
Time Frame	Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26

Outcome Measure Data

Analysis Population Description

PD analysis set included participants who had PD data assessments during this study. Here, 'Overall number of participants analyzed' = participants evaluable for this endpoint. Number analyzed = participants evaluable at specified timepoint.

Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
Measure Participants	10
Baseline	105.8 (14.15)
Day 1, 24 hours postdose	1.1 (2.01)
Week 12, Predose	1.8 (4.67)
Week 12, 60 minutes postdose	0.2 (0.45)
Week 26, Predose	0.5 (1.29)

Adverse Events

Time Frame	Baseline up to the data cut-off date 6 January 2022 (up to approximately 3 years)
Adverse Event Reporting Description	Safety analysis set included all participants who received at least 1 dose of eculizumab.
Arm/Group Title	Eculizumab
Arm/Group Description	Participants received eculizumab weekly by IV infusion during the Primary Evaluation Treatment Period (26 weeks) and the Extension Period (up to 208 weeks). Dosing was initiated with a weekly weight-based induction regimen (Induction Phase) and, thereafter, participants were dosed every 2 weeks (Maintenance Phase). Eculizumab was administered at doses of 300, 600, 900, or 1200 mg, based on the participant's current body weight.
All Cause Mortality
	Eculizumab
	Affected / at Risk (%)	# Events
Total	0/11 (0%)
Serious Adverse Events
	Eculizumab
	Affected / at Risk (%)	# Events
Total	3/11 (27.3%)
General disorders
Pyrexia	1/11 (9.1%)	1
Infections and infestations
Peritonsillar abscess	1/11 (9.1%)	1
Nervous system disorders
Myasthenia gravis	1/11 (9.1%)	3
Myasthenia gravis crisis	1/11 (9.1%)	1
Other (Not Including Serious) Adverse Events
	Eculizumab
	Affected / at Risk (%)	# Events
Total	11/11 (100%)
Blood and lymphatic system disorders
Iron deficiency anaemia	1/11 (9.1%)	1
Leukopenia	1/11 (9.1%)	1
Lymphocytosis	1/11 (9.1%)	1
Monocytosis	1/11 (9.1%)	1
Neutropenia	1/11 (9.1%)	1
Cardiac disorders
Palpitations	2/11 (18.2%)	2
Ear and labyrinth disorders
Ear pain	1/11 (9.1%)	1
Eye disorders
Eye pruritus	1/11 (9.1%)	1
Lacrimation increased	1/11 (9.1%)	1
Ocular hyperaemia	1/11 (9.1%)	1
Gastrointestinal disorders
Abdominal pain	2/11 (18.2%)	2
Diarrhoea	2/11 (18.2%)	2
Vomiting	2/11 (18.2%)	2
Abdominal distension	1/11 (9.1%)	1
Abdominal pain upper	1/11 (9.1%)	1
Constipation	1/11 (9.1%)	2
Flatulence	1/11 (9.1%)	1
Mouth ulceration	1/11 (9.1%)	15
Nausea	1/11 (9.1%)	1
General disorders
Fatigue	2/11 (18.2%)	3
Infusion site extravasation	1/11 (9.1%)	2
Injection site bruising	1/11 (9.1%)	1
Injection site pain	1/11 (9.1%)	1
Vaccination site pain	1/11 (9.1%)	1
Pyrexia	2/11 (18.2%)	4
Infections and infestations
Nasopharyngitis	4/11 (36.4%)	5
Upper respiratory tract infection	2/11 (18.2%)	2
COVID-19	1/11 (9.1%)	1
Cellulitis	1/11 (9.1%)	1
Pharyngitis	1/11 (9.1%)	1
Post viral fatigue syndrome	1/11 (9.1%)	1
Viral infection	1/11 (9.1%)	2
Injury, poisoning and procedural complications
Thermal burn	2/11 (18.2%)	2
Vaccination complication	2/11 (18.2%)	2
Arthropod bite	1/11 (9.1%)	1
Investigations
Glucose urine present	1/11 (9.1%)	1
Electrocardiogram PR prolongation	1/11 (9.1%)	1
Metabolism and nutrition disorders
Decreased appetite	2/11 (18.2%)	2
Ketosis	1/11 (9.1%)	1
Hypokalaemia	1/11 (9.1%)	1
Musculoskeletal and connective tissue disorders
Pain in extremity	3/11 (27.3%)	4
Costochondritis	1/11 (9.1%)	1
Muscle spasms	1/11 (9.1%)	1
Muscle twitching	1/11 (9.1%)	1
Musculoskeletal stiffness	1/11 (9.1%)	1
Myalgia	1/11 (9.1%)	1
Nervous system disorders
Headache	4/11 (36.4%)	12
Dizziness	1/11 (9.1%)	1
Tremor	1/11 (9.1%)	1
Product Issues
Device malfunction	1/11 (9.1%)	1
Psychiatric disorders
Behaviour disorder	1/11 (9.1%)	1
Panic attack	1/11 (9.1%)	1
Renal and urinary disorders
Hypercalciuria	1/11 (9.1%)	1
Respiratory, thoracic and mediastinal disorders
Nasal congestion	2/11 (18.2%)	2
Cough	1/11 (9.1%)	1
Oropharyngeal pain	1/11 (9.1%)	1
Sinus congestion	1/11 (9.1%)	1
Skin and subcutaneous tissue disorders
Acne	1/11 (9.1%)	1
Dry skin	1/11 (9.1%)	2
Eczema	1/11 (9.1%)	7
Pruritus	1/11 (9.1%)	1
Rash	1/11 (9.1%)	1
Urticaria	1/11 (9.1%)	1
Vascular disorders
Poor venous access	1/11 (9.1%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.