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

• ClinicalTrials.gov Identifier: NCT03759366
• Recruitment Status: Recruiting
• First Posted: November 30, 2018
• Last Update Posted: August 19, 2020
• Sponsor: Alexion Pharmaceuticals
• Information provided by (Responsible Party): Alexion Pharmaceuticals

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Myasthenia Gravis; Myasthenia Gravis, Juvenile Form; Myasthenia Gravis, Generalized	Drug: Eculizumab	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 12 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: December 21, 2018
• Estimated Primary Completion Date: June 2021
• Estimated Study Completion Date: July 2025

Arms and Interventions

Arm

Intervention/treatment

Experimental: 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.

Drug: Eculizumab; Eculizumab will be administered by IV infusion.

Outcome Measures

Primary Outcome Measures :

1. Change From Baseline In The QMG Total Score Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline, up to Week 26 (Primary Evaluation Period) and Week 208 (Extension Period) ]

Secondary Outcome Measures :

1. Change From Baseline In The Myasthenia Gravis-Activities Of Daily Living (MG-ADL) Score Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline, up to Week 26 (Primary Evaluation Period) and Week 208 (Extension Period) ]
2. Change From Baseline In The MG Composite (MGC) Score Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline, up to Week 26 (Primary Evaluation Period) and Week 208 (Extension Period) ]
3. Change From Baseline In European Quality Of Life 5-Dimension Youth (EQ-5D-Y) Score Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline, up to Week 26 (Primary Evaluation Period) and Week 208 (Extension Period) ]
4. Change From Baseline In Neurological Quality Of Life (Neuro-QoL) Pediatric Fatigue Score Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline, up to Week 26 (Primary Evaluation Period) and Week 208 (Extension Period) ]
5. Myasthenia Gravis Foundation Of America (MGFA) Post-Interventional Status Over Time Regardless Of Rescue Treatment [ Time Frame: Baseline through Week 26 (Primary Evaluation Period) and Week 208 (Extension Period)] ]
6. Number Of Participants With Clinical Deteriorations, Myasthenic Crises, And Rescue Therapy Use Over Time [ Time Frame: Baseline through Week 26 (Primary Evaluation Period) and Week 208 (Extension Period)] ]
7. Pharmacokinetics: Plasma Concentration Of Eculizumab Over Time [ Time Frame: Baseline through Week 26 ]
8. Free Complement Component 5 (C5) Concentrations Over Time [ Time Frame: Baseline through Week 26 ]
9. Percentage Of Hemolysis (In Vitro Assay) Over Time [ Time Frame: Baseline through Week 26 ]

Eligibility Criteria

• Ages Eligible for Study: 6 Years to 17 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Contacts

Contact: Alexion Pharmaceuticals Inc.; 855-752-2356; clinicaltrials@alexion.com

Locations

United States, California

Children's Hospital Los Angeles, Division of Neurology; Recruiting

Los Angeles, California, United States, 90027

United States, Florida

University of South Florida; Recruiting

Tampa, Florida, United States, 33612

United States, Illinois

Ann & Robert H. Lurie Children's Hospital of Chicago; Recruiting

Chicago, Illinois, United States, 60611

United States, Missouri

University of Missouri-Columbia; Recruiting

Columbia, Missouri, United States, 65211

St. Louis University/SSM Health Cardinal Glennon Children's Hospital; Recruiting

Saint Louis, Missouri, United States, 63104

United States, North Carolina

University of North Carolina at Chapel Hill; Recruiting

Chapel Hill, North Carolina, United States, 27599-1651

United States, Ohio

Akron Children's Hospital; Recruiting

Akron, Ohio, United States, 44308

United States, Pennsylvania

Children's Hospital of Philadelphia; Recruiting

Philadelphia, Pennsylvania, United States, 19104

United States, South Carolina

Medical University of South Carolina; Recruiting

Charleston, South Carolina, United States, 29425-8572

Japan

Chiba University Hospital; Recruiting

Chiba-shi, Chiba-Ken, Japan, 260-8677

Saitama Medical University; Recruiting

Saitama, Iruma-gun, Japan, 350-0495

Teikyo University; Recruiting

Tokyo, Itabasha-ku, Japan

Tokyo Women's Medical University Hospital; Recruiting

Tokyo, Shinjuku-ku, Japan, 162-8666

Dokkyo Medical University Hospital; Recruiting

Mibu, Tochigi, Japan, 3210293

Sponsors and Collaborators

Alexion Pharmaceuticals

More Information

• Responsible Party: Alexion Pharmaceuticals
• ClinicalTrials.gov Identifier: NCT03759366
• Other Study ID Numbers: ECU-MG-303
• First Posted: November 30, 2018
• Last Update Posted: August 19, 2020
• Last Verified: March 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Alexion Pharmaceuticals:

Myasthenia Gravis; Myasthenia Gravis, Generalized

Additional relevant MeSH terms:

Muscle Weakness; Myasthenia Gravis; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Pathologic Processes; Autoimmune Diseases of the Nervous System; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases