Neoplasms

Nervous System Diseases

Immune System Diseases

All Conditions

Musculoskeletal Diseases

Symptoms and General Pathology

Rare Diseases

Myasthenia Gravis

Muscle Weakness

Paresis

Asthenia

Muscular Diseases

Neuromuscular Manifestations

Neurologic Manifestations

Syndrome

Paraneoplastic Syndromes

Paraneoplastic Syndromes, Nervous System

Nervous System Neoplasms

Autoimmune Diseases

Autoimmune Diseases of the Nervous System

Neurodegenerative Diseases

Neuromuscular Junction Diseases

Neuromuscular Diseases

All Drugs and Chemicals

Eculizumab

Complement System Proteins

Immunosuppressive Agents

Immunologic Factors

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.

Eculizumab will be administered by IV infusion.

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.

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.

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

An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Eculizumab in Pediatric Patients With Refractory Generalized Myasthenia Gravis

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.

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.

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.

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.

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'.

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.

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

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.

Alexion Pharmaceuticals, Inc.

Safety analysis set included all participants who received at least 1 dose of eculizumab.

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.

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race

Race/Ethnicity, Customized

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 most severe disease.

QMG Total Score

Full analysis set included all participants who received at least 1 dose of eculizumab.

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.

Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment

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.

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

Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment

Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment

Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment

Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment

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

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

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

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

Clinical Deterioration

MG Crisis

Requiring Rescue Therapy

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

Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use

Day 1, 24 hours postdose (n = 11)

Week 12, Predose

Week 12, 60 minutes postdose

Week 26, Predose

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

Pharmacokinetics (PK): Serum Concentration Of Eculizumab

Baseline

Day 1, 24 hours postdose

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

Pharmacodynamics (PD): Serum Free Complement Component 5 (C5) Concentrations

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.

PD: Percentage of Hemolysis (In Vitro Assay)

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.

Spots Global Cancer Trial Database for A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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