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

• Register: ClinicalTrials.gov
• Last refreshed on: 7 August 2023
• Main ID: NCT03759366
• Date of registration: 26/11/2018
• Prospective Registration: Yes
• Primary sponsor: Alexion
• Public title: A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG)
• Scientific title: An Open-Label, Multicenter Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Eculizumab in Pediatric Patients With Refractory Generalized Myasthenia Gravis
• Date of first enrolment: December 21, 2018
• Target sample size: 11
• Recruitment status: Active, not recruiting
• URL: https://clinicaltrials.gov/ct2/show/NCT03759366
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Japan, Netherlands, United States

Key inclusion & exclusion 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.



Age minimum: 6 Years
Age maximum: 17 Years
Gender: All

Health Condition(s) or Problem(s) studied

Myasthenia Gravis, Generalized

Myasthenia Gravis

Myasthenia Gravis, Juvenile Form

Intervention(s)

Drug: Eculizumab

Primary Outcome(s)

Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment [Time Frame: Baseline, Week 26]

Secondary Outcome(s)

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 [Time Frame: Baseline, Week 26]

Percentage of Participants With =3-Point Reduction in the MG-ADL Total Score With No Rescue Treatment [Time Frame: Week 26]

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

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

Percentage of Participants With =3-Point Reduction in the MG-ADL Total Score Regardless of Rescue Treatment [Time Frame: 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 [Time Frame: Baseline, Week 26]

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]

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]

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

Percentage of Participants With =5-Point Reduction in the QMG Total Score Regardless of Rescue Treatment [Time Frame: Week 26]

Percentage of Participants With =5-Point Reduction in the QMG Total Score With No Rescue Treatment [Time Frame: Week 26]

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]

Secondary ID(s)

ECU-MG-303

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 25/08/2022
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03759366