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

Alexion Pharmaceuticals, Inc.1 site in 1 country12 target enrollmentDecember 28, 2018

ConditionsMyasthenia Gravis Myasthenia Gravis, Juvenile Form Myasthenia Gravis, Generalized

InterventionsEculizumab

DrugsEculizumab

Overview

Phase: Phase 3
Intervention: Eculizumab
Conditions: Myasthenia Gravis
Sponsor: Alexion Pharmaceuticals, Inc.
Enrollment: 12
Locations: 1
Primary Endpoint: Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment
Status: Completed
Last Updated: last year

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

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.

Registry

clinicaltrials.gov

Start Date

December 28, 2018

End Date

November 6, 2023

Last Updated

last year

Study Type

Interventional

Study Design

Single Group

Sex

All

Investigators

Sponsor

Alexion Pharmaceuticals, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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.

Arms & Interventions

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.

Intervention: Eculizumab

Outcomes

Primary Outcomes

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

Time Frame: 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 scores indicating more severe disease.

Secondary Outcomes

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)
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment(Week 26)
Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment(Week 26)
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment(Week 26)
Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment(Week 26)
Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment(Baseline, Week 26)
Change From Baseline in the European Quality of Life 5-Dimension Youth Version (EQ-5D-Y) Visual Analogue Scale (VAS) Score at Week 26 Regardless of Rescue Treatment(Baseline, Week 26)
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)
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)
Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use(Baseline up to Week 26)
Pharmacokinetics (PK): Serum Concentration Of Eculizumab(24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26)
Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations(Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26)
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)
Change From Baseline in the QMG Total Score at Week 52 Regardless of Rescue Treatment(Baseline, Week 52)