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

NCT03759366 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: ECU-MG-3032016-001384-37
• Study Type: interventional
• Target: 12
• Locations: 2 countries
• Sites: 11

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.

Conditions

Myasthenia Gravis; Myasthenia Gravis, Juvenile Form; Myasthenia Gravis, Generalized

Keywords

Myasthenia Gravis; Myasthenia Gravis, Generalized

Outcome Measures

Primary Outcomes (1)

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

  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.

  Baseline, Week 26

Secondary Outcomes (14)

• 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

Study Arms (1)

Eculizumab Intravenous (IV) Infusion

EXPERIMENTAL

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

Interventions

Eculizumab DRUG

Eculizumab will be administered by IV infusion.

Eculizumab Intravenous (IV) Infusion

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Alexion Pharmaceuticals, Inc.: lead

Study Sites (11)

Research Site

Los Angeles, California, 90078, United States

Location

Research Site

Tampa, Florida, 33612, United States

Location

Research Site

Chicago, Illinois, 60611, United States

Location

Research Site

Columbia, Missouri, 65201, United States

Location

Research Site

Chapel Hill, North Carolina, 27599, United States

Location

Research Site

Akron, Ohio, 44308, United States

Location

Research Site

Philadelphia, Pennsylvania, 19104, United States

Location

Research Site

Charleston, South Carolina, 29425, United States

Location

Research Site

Iruma-Gun, 350-0495, Japan

Location

Research Site

Itabashi-ku, 173-0003, Japan

Location

Research Site

Shinjuku-ku, 162-8666, Japan

Location

Related Links

• Related Info

MeSH Terms

Conditions

Myasthenia Gravis

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Alexion Europe SAS European Clinical Trial Information
• Organization: Alexion Pharmaceuticals Inc.

clinicaltrials.eu@alexion.com

7 87148158

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 26, 2018
• First Posted: November 30, 2018
• Study Start: December 28, 2018
• Primary Completion: January 6, 2022
• Study Completion: November 6, 2023
• Last Updated: December 11, 2024
• Results First Posted: August 25, 2022

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will not share

Locations

JP (3); US (8)