Myasthenia Gravis Inebilizumab Trial

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled, Phase 3, parallel-group study with optional open-label extension.

Detailed Description
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This study is a phase 3, randomized, double-blind, placebo-controlled study, to be conducted at approximately 120 study sites. Approximately 270 participants (188 acetylcholine receptor antibody positive [AChR-Ab+] and 82 muscle-specific tyrosine kinase antibody positive [MuSK-Ab+]) will be enrolled. Participants with Myasthenia Gravis (MG) who are positive for anti-AChR or anti-MuSK antibodies will be enrolled and analyzed separately as 2 populations: (1) AChR-Ab+ and (2) MuSK-Ab+. Patients who do not have anti-AChR or anti-MuSK antibodies will not be enrolled. Patients with Myasthenia Gravis Foundation of America (MGFA) classification II, III, or IV disease, Myasthenia Gravis Activities of Daily Living (MG-ADL) score at screening and randomization between 6 and 10 with > 50% of this score attributed to non-ocular items, or an MG-ADL score >=11, Quantitative Myasthenia Gravis (QMG) score >= 11 at the time of screening and randomization, and use of a corticosteroid and/or non-steroidal immunosuppressant will be included in the study. All subjects who complete the randomized controlled period (RCP) will have the option to enroll in a 3-year (156 weeks) open-label period.

Official Title
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A Randomized, Double-blind, Multicenter, Placebo-controlled Phase 3 Study With Open-label Period to Evaluate the Efficacy and Safety of Inebilizumab in Adults With Myasthenia Gravis

Conditions
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Myasthenia Gravis

Intervention / Treatment
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* Drug: inebilizumab
* Drug: IV Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of MG with anti-AChR or anti-MuSK antibody. MGFA Clinical Classification Class II, III, or IV. MG-ADL score of 6 or greater at screening and at randomization with > 50% of this score attributed to non-ocular items. QMG score of 11 or greater. Participants must be on: Corticosteroids only, with no dose increase within 4 weeks prior to randomization, or One allowed non-steroidal immunosuppressive therapy (IST), with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization, or Combination of (1) corticosteroids with no dose increase within 4 weeks prior to randomization and (2) one allowed non-steroidal IST with continuous use for at least 6 months prior to randomization and no dose increase within 4 months prior to randomization. Allowed ISTs, alone or in combination with corticosteroids, are azathioprine, mycophenolate mofetil, and mycophenolic acid. Exclusion Criteria: Receipt of the following medications within the 4 weeks prior to Day 1: Cyclosporine (except eye drops) Tacrolimus (except topical) Methotrexate Current use of: Corticosteroids (Prednisone > 40 milligram (mg)/day or > 80 mg over a 2-day period (or equivalent dose of other corticosteroids). Acetylcholinesterase inhibitors (pyridostigmine) > 480 mg/day) or unstable dose in the 2 weeks prior to Day 1. Azathioprine > 3 mg/kilogram (kg)/day Mycophenolate mofetil > 3 grams/day or mycophenolic acid > 1440 mg/day Any IST, alone or in combination with corticosteroids, except for azathioprine, mycophenolate mofetil, and mycophenolic acid.

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
Interventional Model Description: A Randomized, Double-blind, Multicenter, Placebo-controlled Phase 3 Study with Open-label Period
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Inebilizumab, (AChR-Ab+) MG<br>Participants will receive inebilizumab administered intravenously (IV) on Days 1, 15, and 183 of the RCP. Participants who elect to enter the open label phase (OLP) will receive inebilizumab administered IV on OLP Days 1, IV placebo on OLP Day 15 (to avoid potential unblinding), and inebilizumab IV on OLP Days 183, 365, 547, 729, and 911. | Drug: inebilizumab<br>* Participants will receive IV inebilizumab<br>* Other names: VIB0551;|
| Placebo Comparator: Placebo, (AChR-Ab+) MG<br>Participants will receive placebo administered IV on Days 1, 15, and 183 of the RCP. Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Days 1,15, 183, 365, 547, 729, and 911. | Drug: IV Placebo<br>* Participants will receive IV placebo matched to inebilizumab<br>|
| Experimental: Inebilizumab, (MuSK-Ab+) MG<br>Participants will receive inebilizumab administered IV on Days 1 and 15 of the RCP. Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Day 1, IV placebo on OLP Day 15 (to avoid potential unblinding), and inebilizumab IV on OLP Days 183, 365, 547, 729, and 911. | Drug: inebilizumab<br>* Participants will receive IV inebilizumab<br>* Other names: VIB0551;|
| Placebo Comparator: Placebo, (MuSK-Ab+) MG<br>Participants will receive placebo administered IV on Days 1 and 15 of the RCP. Participants who elect to enter the OLP will receive inebilizumab administered IV on OLP Days 1,15, 183, 365, 547, 729, and 911. | Drug: IV Placebo<br>* Participants will receive IV placebo matched to inebilizumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in Myasthenia Gravis Activities of Daily Living (MG-ADL) Profile score. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Quantitative Myasthenia Gravis (QMG) scores. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 
| Proportion of participants with both ≥ 3-point improvement in MG-ADL and did not initiate rescue therapy. |  | Between Week 44 and Week 52 for AChR-Ab+ population and Week 22 and Week 26 for MuSK-Ab+ population | 
| Change in MG-ADL at Week 26 in the AChR-Ab+ population. (AChR-Ab+ Only) |  | Week 26 for AChR-Ab+ population | 
| Time to first exacerbation. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 
| Change in Myasthenia Gravis Composite (MGC) score. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 
| Change in Myasthenia Gravis Quality of Life-15, revised (MGQOL-15r) score. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 
| Change in Patient Global Impression of Change (PGIC) score. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 
| Number of participants with treatment-emergent adverse events (TEAEs), adverse events of special interest (AESIs), and treatment-emergent serious adverse events (TESAEs) during the RCP and OLP. |  | Week 52 for AChR-Ab+ population and Week 26 for MuSK-Ab+ population | 

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