Phase 3 Study to Assess the Efficacy and Safety of Batoclimab as Induction and Maintenance Therapy in Adult Participants With Generalized Myasthenia Gravis

Study Overview
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Brief Summary
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The purpose of this 3-period study is to confirm the efficacy and safety of batoclimab in participants with gMG. In Period 1, participants will be randomized 1:1:1 to receive batoclimab 680 milligrams (mg) subcutaneously (SC) once a week (QW) or 340 mg SC QW or placebo. The primary efficacy endpoint will be assessed by change in the myasthenia gravis activities of daily living (MG- ADL) score in acetylcholine receptor antibody seropositive (AChRAb+) participants. In Period 2, participants previously treated with batoclimab will be re-randomized to stay on batoclimab (340 mg SC QW or 340 mg SC every two weeks) or receive placebo treatment. The secondary endpoint of maintenance of efficacy will be assessed by change in the MG- ADL score in AChRAb+ participants. Participants demonstrating a response to batoclimab during either Period 1 or 2 may enter the long-term extension (Period 3).

Official Title
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A Phase 3, Multi-center, Randomized, Quadruple-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Batoclimab as Induction and Maintenance Therapy in Adult Participants With Generalized Myasthenia Gravis (gMG)

Conditions
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Generalized Myasthenia Gravis

Intervention / Treatment
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* Drug: Batoclimab 680 mg SC weekly
* Drug: Batoclimab 340 mg SC weekly
* Drug: Matching Placebo SC
* Drug: Batoclimab 340 mg SC bi-weekly


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Are ≥ 18 years of age at the Screening Visit. Have mild to severe gMG by Myasthenia Gravis Foundation of America (MGFA) classification Class II, III, or IVa at the Screening Visit. Have a QMG score ≥ 11 at the Screening and Baseline Visits. Have a MG-ADL score of ≥ 5 at the Screening and Baseline Visits. Additional inclusion criteria are defined in the protocol. Exclusion Criteria: Have experienced myasthenic crisis within 3 months of the Screening Visit. Have had a thymectomy performed < 6 months prior to the Screening Visit or have a planned thymectomy during the study period. Have any active or untreated malignant thymoma. Have received any agent or therapy (exclusive of those identified within inclusion criteria) with immunosuppressive properties (e.g., stem cell therapy, chemotherapies, etc.) within the past year. Have used anti-FcRN treatment within 3 months prior to the Screening Visit or have a documented history of non-response to prior anti-FcRN treatment. Additional exclusion criteria are defined in the protocol.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Batoclimab Induction Dose 1 (Period 1)<br> | Drug: Batoclimab 680 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Batoclimab Induction Dose 2 (Period 1)<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Placebo Comparator: Placebo Induction Dose (Period 1)<br> | Drug: Matching Placebo SC<br>* Placebo<br>|
| Experimental: Batoclimab Maintenance Dose 1 (Period 2)<br> | Drug: Batoclimab 340 mg SC weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Experimental: Batoclimab Maintenance Dose 2 (Period 2)<br> | Drug: Batoclimab 340 mg SC bi-weekly<br>* Batoclimab is a fully human anti-neonatal fragment crystallizable receptor (FcRn) monoclonal antibody<br>* Other names: IMVT-1401;|
| Placebo Comparator: Placebo Maintenance Dose (Period 2)<br> | Drug: Matching Placebo SC<br>* Placebo<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) score in acetylcholine receptor (AChR) Ab seropositive (AChRAb+) participants | MG-ADL is an 8-item, participant-reported questionnaire that assesses gMG symptoms and their effects on activities of daily living. Each item is assessed on a 4-point scale where a score of 0 represents normal function and a score of 3 represents loss of ability to perform that function. Total score ranges from 0 to 24, with higher scores indicating greater functional impairment and disability. | Baseline (Day 1) to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from Baseline in Quantitative Myasthenia Gravis (QMG) score in AChRAb+ participants | QMG is clinician-reported assessment to evaluate muscle weakness in participants with MG. The QMG consists of 13 items ranging from 0 to 3 with 3 being the most severe. Total score ranges from 0 to 39, with higher scores representing greater impairment. | Baseline (Day 1) to Week 12 | 
| Change from Baseline in MG-ADL score for AChRAb+ randomized withdrawal participants |  | Baseline (Week 12) to Week 24 | 
| Percentage of AChRAb+ participants with greater than equal to (>=) 3-point improvement in QMG score |  | Up to Week 12 | 
| Percentage of AChRAb+ participants achieving MG-ADL score of 0 or 1 by Week 12 |  | Up to Week 12 | 
| Change from Baseline in MG-ADL score in AChRAB- (AChRAB negative) participants |  | Baseline (Day 1) to Week 12 | 
| Percentage of Participants with Treatment Emergent Adverse Events (TEAEs) | An adverse event (AE) is defined as any untoward medical occurrence in a participant who has either been administered a study drug or has undergone study procedures. | Up to 76 Weeks | 
| Percentage of Participants With Clinically Significant Changes in Vital Sign Measurements | Vital signs, including systolic and diastolic blood pressures, pulse rate, respiratory rate, and temperature will be obtained and recorded at specified timepoints. All vital sign measures will be obtained with the participant in the supine position and having rested for at least 5 minutes. | Up to 76 Weeks | 
| Number of Participants with Clinically Significant Changes in Laboratory Results | Blood samples will be collected at specified timepoints for the analysis of laboratory parameters including clinical chemistry, hematology and urinalysis. | Up to 76 Weeks | 
| Percentage of participants with clinical laboratory-related TEAEs or treatment emergent laboratory abnormalities. |  | Up to 76 Weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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monoclonal antibody, batoclimab, IMVT-1401, Myasthenia Gravis, acetylcholine receptor, RVT-1401