Phase 3 Randomized Quadruple-Blind Study on Batoclimab Efficacy and Safety in Adult Generalized Myasthenia Gravis Patients

The primary objective of this study is to evaluate the **efficacy** of batoclimab, administered at doses of 680 mg or 340 mg subcutaneously once weekly, compared to placebo as induction therapy in participants with acetylcholine receptor antibody-positive (**AChRAb+**) generalized myasthenia gravis (**gMG**). This is assessed by the change in the Myasthenia Gravis Activities of Daily Living (**MG-ADL**) score. The MG-ADL score is a clinically relevant measure as it reflects the impact of the disease on daily functioning, providing insight into the therapeutic benefit of batoclimab in improving patient quality of life.

Secondary objectives include evaluating the efficacy of batoclimab at the same dosages compared to placebo, as assessed by the change in the Quantitative Myasthenia Gravis (**QMG**) score. The QMG score is a critical measure of disease severity and response to treatment, offering additional data on the potential benefits of batoclimab in managing gMG symptoms.

The clinical trial involves a total of **88 participants** diagnosed with **Generalized Myasthenia Gravis (gMG)**. The study population includes both male and female subjects, aged 18 years and older, who have been classified under the Myasthenia Gravis Foundation of America (MGFA) classification as Class II, III, or IVa. Participants were selected based on specific criteria, including a Quantitative Myasthenia Gravis (QMG) score of 11 or higher and a Myasthenia Gravis Activities of Daily Living (MG-ADL) score of 5 or higher at both the Screening and Baseline Visits. The trial population is characterized by a range of mild to severe gMG symptoms. The study does not specify particular lifestyle considerations such as diet or physical activity. The selection process also includes vulnerable populations, ensuring a comprehensive evaluation of the treatment's efficacy across diverse demographic groups.

The clinical trial is a **randomized**, quadruple-blind, placebo-controlled study designed to evaluate the efficacy and safety of **Batoclimab** as induction and maintenance therapy in adult participants with **Generalized Myasthenia Gravis (gMG)**. The trial is structured to include multiple phases, with an estimated duration from June 2022 to November 2027. Participants will be randomly assigned to receive either Batoclimab or a placebo, with the study employing a double-blind methodology to ensure that neither the participants nor the investigators are aware of the treatment allocations. The primary objective is to assess the change in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score over a 12-week period for AChRAb+ participants.

The trial will commence with a screening visit to confirm eligibility, which includes criteria such as being 18 years or older and having a Myasthenia Gravis Foundation of America (MGFA) classification of Class II, III, or IVa. Participants must also have a Quantitative Myasthenia Gravis (QMG) score of 11 or higher and an MG-ADL score of 5 or higher at both the screening and baseline visits. Following the screening, eligible participants will enter the induction phase, receiving weekly subcutaneous injections of either Batoclimab or placebo. The primary endpoint will be evaluated at Week 12, with secondary endpoints assessed at various intervals, including changes in QMG scores and the proportion of participants achieving significant improvements.

Participants will be involved in the study for a maximum treatment period of 128 weeks, with regular follow-up visits to monitor safety and efficacy outcomes. The end-of-study visit will conclude the participant's involvement, during which final assessments will be conducted. Conditions that may lead to early termination from the study include adverse events, withdrawal of consent, or non-compliance with the study protocol. The trial aims to provide comprehensive data on the therapeutic potential of Batoclimab in managing gMG, contributing to the understanding of its role in improving patient outcomes.

The clinical trial involves the administration of **Batoclimab**, a **solution for injection** developed by Immunovant Sciences GmbH. Batoclimab is an investigational medicinal product designed for subcutaneous administration. The active substance, batoclimab, is a protein-based therapeutic agent, specifically a human monoclonal antibody targeting the human FcRn receptor. The trial protocol specifies two dosing regimens for Batoclimab: 680 mg and 340 mg, both administered once weekly (QW). The maximum daily dose is 680 mg, with a total maximum dose of 47,600 mg over a treatment period of up to 128 days. The study aims to evaluate the efficacy of Batoclimab as an induction and maintenance therapy in adult participants with generalized myasthenia gravis (gMG), particularly those who are AChRAb+.

The trial also includes a **placebo** group, which serves as a comparator to the experimental treatment. The placebo is formulated to be identical in appearance to the investigational medicinal product but contains no active substance. This design ensures that any observed effects can be attributed to the active treatment rather than psychological or other non-specific effects. The placebo is administered following the same schedule and route as Batoclimab, maintaining the study's quadruple-blind design to ensure unbiased results. Participant compliance with the dosing schedule is monitored throughout the study to ensure adherence to the protocol and to accurately assess the treatment's efficacy and safety.

The efficacy of Batoclimab in the treatment of **Generalized Myasthenia Gravis (gMG)** will be assessed through a Phase 3, multi-center, randomized, quadruple-blind, placebo-controlled study. The primary endpoint for evaluating efficacy is the change from Period 1 baseline in the Myasthenia Gravis Activities of Daily Living (MG-ADL) score to Week 12 for AChRAb+ participants. Secondary endpoints include the change from Period 1 baseline in the Quantitative Myasthenia Gravis (QMG) score to Week 12 for AChRAb+ participants, the change from Period 2 baseline in MG-ADL score to Week 24 for AChRAb+ randomized withdrawal participants, and the proportion of AChRAb+ participants with a ≥ 3-point improvement in QMG from Period 1 baseline to Week 12. Additionally, the proportion of AChRAb+ participants achieving an MG-ADL score of 0 or 1 by Week 12 and the change from Period 1 baseline in MG-ADL score to Week 12 for AChRAb- participants will be evaluated.

The MG-ADL and QMG scores will be collected at specified timepoints, including baseline, Week 12, and Week 24, using validated scales. These scores will be analyzed to determine the efficacy of Batoclimab compared to placebo. The study will involve adult participants with mild to severe gMG, classified as Class II, III, or IVa by the Myasthenia Gravis Foundation of America (MGFA) classification, and will require a QMG score of ≥ 11 and an MG-ADL score of ≥ 5 at the Screening and Baseline Visits. The trial is designed to explore both the induction and maintenance therapy effects of Batoclimab, administered subcutaneously at doses of 680 mg or 340 mg weekly.