Safety and Efficacy of Eculizumab in Refractory Generalized Myasthenia Gravis (REGAIN Study)

Study Overview
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Brief Summary
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The purpose of this study is to determine if eculizumab is safe and effective for the treatment of refractory generalized Myasthenia Gravis.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of Eculizumab in Subjects With Refractory Generalized Myasthenia Gravis (gMG)

Conditions
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Refractory Generalized Myasthenia Gravis

Intervention / Treatment
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* Biological: Eculizumab
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female patients ≥18 years old Diagnosis of MG made by the following tests: Positive serologic test for anti-AChR Abs as confirmed at screening, and One of the following: History of abnormal neuromuscular transmission test demonstrated by single-fiber electromyography (SFEMG) or repetitive nerve stimulation, or History of positive anticholinesterase test, e.g. edrophonium chloride test, or Subject has demonstrated improvement in MG signs on oral cholinesterase inhibitors, as assessed by the treating physician. MGFA Clinical Classification Class II to IV at screening. MG-ADL total score must be ≥6 at screening and Randomization (Day 1). Subjects who have: Failed treatment with at least two immunosuppressive agents. Or, Failed treatment with at least one immunosuppressive agent and require chronic plasma exchange or IVIg Key Exclusion Criteria: History of thymoma or other neoplasms of the thymus History of thymectomy within 12 months prior to screening MGFA Class I or MG crisis at screening (MGFA Class V) Use of rituximab within 6 months prior to screening Use of IVIg or PE within 4 weeks prior to Randomization (Day 1)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Eculizumab<br>Biological/Vaccine: Eculizumab; Induction phase: 3 vials of study drug (equivalent to 900 mg of eculizumab) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (equivalent to 1200 mg of eculizumab) 1 week later for the fifth dose (Week 4); Maintenance phase: 4 vials of study drug (equivalent to 1200 mg of eculizumab) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26). | Biological: Eculizumab<br>* Induction Phase: 900 mg IV weekly X 4 Maintenance Phase: 1200 mg IV every 2 weeks during Weeks 4-26<br>|
| Placebo Comparator: Placebo<br>Placebo contains the same buffer components without the active ingredient; Induction phase: 3 vials of study drug (placebo) weekly for 4 doses (every 7 days ± 2 days) followed by 4 vials of study drug (placebo) 1 week later for the fifth dose (Week 4); Maintenance phase: 4 vials of study drug (placebo) every 2 weeks (14 days ± 2 days) from the fifth dose onwards (Week 6 through Week 26). | Drug: Placebo<br>* Placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Myasthenia Gravis Activities of Daily Living Profile (MG-ADL): Change From Baseline in MG-ADL Total Score at Week 26 by Worst-Rank Analysis of Covariance (ANCOVA) | In the Worst-Rank analysis, the 125 total patients were ranked from best outcome (rank/score of 1) to worst outcome (rank/score of 125). | End of study (Week 26) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Myasthenia Gravis, Eculizumab, safety, efficacy