Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled, parallel-group study with optional open-label extension.

Detailed Description
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This study is a randomized, double-blind, placebo-controlled study, to be conducted at 6 study sites. Approximately 64 subjects will be enrolled. Patients with MG who are positive for anti-AChR antibodies will be enrolled. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with MGFA classification II, III, or IV disease, MG-ADL score ≥ 5, QMG score ≥ 11, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study. All subjects who complete the randomized controlled period will have the option to enroll in a 1-year open-label period.

Official Title
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A Multi-center, Randomized, Double-blind, Placebo-controlled Clinical Trial of the Efficacy and Safety of Tocilizumab in the Treatment of Generalized Myasthenia Gravis

Conditions
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Myasthenia Gravis, Generalized

Intervention / Treatment
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* Drug: Tocilizumab Injectable Product


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MG with anti-AChRantibody. MGFA Clinical Classification Class II, III, or IV. MG-ADL score of 5 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items. QMG score of 11 or greater. Subjects must be on: Cholinesterase inhibitor, with no dose increase within 4 weeks prior to randomization; Corticosteroids, with no dose increase within 4 weeks prior to randomization; or/and c. non-steroidal IST (including azathioprine, mycophenolate mofetil, tacrolimus, cyclosporine A), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization. Exclusion Criteria: Participants had clinically relevant active infections (such as sepsis, pneumonia, or abscess) or severe infections (resulting in hospitalization or requiring antibiotic treatment) in the 4 weeks before randomization; Those with a history of high-risk tuberculosis infection, acquired tuberculosis infection, and chronic hepatitis; Human immunodeficiency virus (HIV) infection; Thymomas that have received thymectomy or planned thymectomy during RCP within 6 months before randomization, or require chemotherapy and/or radiotherapy at any time; Received rituximab treatment in the past 6 months before randomization; Received tocilizumab or eculizumab treatment within 3 months before randomization; Received IVIG or plasma exchange within 4 weeks before randomization; Unresected thymoma. History of other tumor diseases.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Tocilizumab<br>Participants will receive tocilizumab administered intravenously (IV) on weeks 1,5,9 and 13 of the randomized controlled period. | Drug: Tocilizumab Injectable Product<br>* Participants will receive IV tocilizumab<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo administered intravenously (IV) on weeks 1,5,9 and 13 of the randomized controlled period. | Drug: Tocilizumab Injectable Product<br>* Participants will receive IV tocilizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quantitative Myasthenia Gravis (QMG) scores. |  | 16 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects with both (1) ≥ 3-point improvement in QMG and (2) lasts ≥4 weeks |  | 16 weeks | 
| Proportion of subjects with both (1) ≥ 2-point improvement in MG-ADL and (2) lasts ≥4 weeks |  | 16 weeks | 
| Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score. |  | 16 weeks | 
| Change in Myasthenia Gravis Composite (MGC) score |  | 16 weeks | 
| Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score. |  | 16 weeks | 
| Change in Myasthenia Gravis Impairment Index (MGII) score. |  | 16 weeks | 
| Number of participants with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and treatment-emergent serious adverse events (TESAEs) during the randomized controlled period and open-label period. |  | 16 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Generalized Myasthenia Gravis, Tocilizumab