Clinical trial NCT03759366: A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Myasthenia Gravis
Myasthenia Gravis, Juvenile Form
Myasthenia Gravis, Generalized
Keywords: Myasthenia Gravis
Myasthenia Gravis, Generalized
Lead sponsor: Alexion Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2018-11-30
Enrollment: 12
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment
timeFrame: Baseline, Week 26
Secondary outcomes:
measure: Change From Baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) Total Score at Week 26 Regardless of Rescue Treatment
timeFrame: Baseline, Week 26
measure: Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment
timeFrame: Week 26
measure: Percentage of Participants With ≥3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment
timeFrame: Week 26
measure: Percentage of Participants With ≥5-Point Reduction in the QMG Total Score With No Rescue Treatment
timeFrame: Week 26
measure: Percentage of Participants With ≥5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment
timeFrame: Week 26
measure: Change From Baseline in the Myasthenia Gravis Composite (MGC) Scale Total Score at Week 26 Regardless of Rescue Treatment
timeFrame: Baseline, Week 26
measure: 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
timeFrame: Baseline, Week 26
measure: Change From Baseline in the Neurological Quality of Life-Fatigue Questionnaire (Neuro-QoL Pediatric Fatigue) Total Score at Week 26 Regardless of Rescue Treatment
timeFrame: Baseline, Week 26
measure: Number of Participants in Each Category of the Myasthenia Gravis Foundation of America Post-Intervention Status (MGFAPIS) Regardless of Rescue Treatment at Week 26
timeFrame: Week 26
measure: Percentage of Participants With Clinical Deteriorations, Myasthenic Crises, and Rescue Therapy Use
timeFrame: Baseline up to Week 26
measure: Pharmacokinetics (PK): Serum Concentration Of Eculizumab
timeFrame: 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
measure: Pharmacodynamics (PD): Serum Free Complement Component 5 Concentrations
timeFrame: Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
measure: PD: Percentage of Hemolysis (In Vitro Assay)
timeFrame: Baseline; 24 hours postdose on Day 1; predose and 60 minutes postdose at Week 12; predose at Week 26
measure: Change From Baseline in the QMG Total Score at Week 52 Regardless of Rescue Treatment
timeFrame: Baseline, Week 52
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Research Site
state: California
city: Tampa
country: United States
facility: Research Site
state: Florida
city: Chicago
country: United States
facility: Research Site
state: Illinois
city: Columbia
country: United States
facility: Research Site
state: Missouri
city: Chapel Hill
country: United States
facility: Research Site
state: North Carolina
city: Akron
country: United States
facility: Research Site
state: Ohio
city: Philadelphia
country: United States
facility: Research Site
state: Pennsylvania
city: Charleston
country: United States
facility: Research Site
state: South Carolina
city: Iruma-Gun
country: Japan
facility: Research Site
city: Itabashi-ku
country: Japan
facility: Research Site
city: Shinjuku-ku
country: Japan
facility: Research Site
Study officials:
References: