Efficacy and Safety Study of Nipocalimab IV Infusions for Adults With Generalized Myasthenia Gravis

INTERVENTION: Product Name: Nipocalimab Product Code: JNJ‐80202135 Pharmaceutical Form: Solution for infusion INN or Proposed INN: Nipocalimab CAS Number: 2211985‐36‐1 Current Sponsor code: JNJ‐80202135 Other descriptive name: M281 Concentration unit: mg/ml milligram(s)/millilitre Concentration type: equal Concentration number: 30‐ Pharmaceutical form of the placebo: Solution for infusion Route of administration of the placebo: Intravenous use CONDITION: Myasthenia gravis (MG). ; MedDRA version: 21.1 Level: PT Classification code 10028417 Term: Myasthenia gravis System Organ Class: 10029205 ‐ Nervous system disorders Therapeutic area: Diseases [C] ‐ Musculoskeletal Diseases [C05] PRIMARY OUTCOME: Main Objective: To evaluate the efficacy of nipocalimab compared to placebo based on the Myasthenia Gravis‐Activities of Daily Living (MG‐ADL) scale, in; seropositive generalized myasthenia gravis (gMG) participants when treatment is taken as directed. Primary end point(s): Average change from baseline (screening and Day 1) in MG‐ADL total score over Weeks 22, 23 and 24. Secondary Objective: ‐ To evaluate the efficacy of nipocalimab compared to placebo based on the Quantitative Myasthenia Gravis (QMG) scale, in seropositive gMG; participants when treatment is taken as directed.; ‐ To evaluate the clinically important individual response of nipocalimab compared to placebo based on the MG‐ADL scale, in seropositive gMG participants when treatment is taken as directed.; ‐ To evaluate the efficacy of nipocalimab loading dose compared to placebo based on the MG‐ADL scale, in seropositive gMG participants when treatment is taken as directed.; ‐ To evaluate the effect of nipocalimab compared to placebo on gMG symptom remission based on the MG‐ADL scale, in seropositive gMG participants when treatment is taken as directed.; ‐To evaluate sustainability of therapeutic response of nipocalimab; compared to placebo based on the MGADL scale, in seropositive gMG participants when treatment is taken as directed. Timepoint(s) of evaluation of this end point: Throughout the double‐blind phase of the study. SECONDARY OUTCOME: Secondary end point(s): 1. The average change in the QMG score over Weeks 22 and 24. Analyzed using a similar method (appropriate for the region) as for the primary efficacy endpoint, but since the QMG is not assessed at Week 23, the contrast will average the change from baseline over Weeks 22 and 24 of the double‐blind placebo‐controlled phase.; 2. Percentage of participants whose average MG‐ADL total score over weeks 22, 23 and 24 of the double blind, placebo‐controlled phase is at least a 2‐point improvement compared to baseline. The average score for a participant is the average of the non‐missing values at Weeks 22, 23 and 24. A participant must have a non‐missing value at Week 24 and at least 1 non‐missing value at Week 22 or 23 in order to have a non‐missing average score. A participant with a missing average score will be considered a nonresponder. Analyzed by Cochran‐Mantel‐Haenszel test controlling for the baseline MG‐ADL total score randomization strata (=9, >9), autoantibody status, and region.; 3. Loading dose response, defined for each participant as improvement in the MG‐ADL total =2 points at Week 1 and/or Week 2. A participant with a missing assessment at either time point will be considered a nonresponder at that time point. Analyzed by Cochran‐Mantel‐Haenszel test controlling for the baseline MG‐ADL total score randomization strata (=9, >9), autoantibody status, and region.; 4. Symptom remission, defined as the average percentage of participants with MG‐ADL score of 0 or 1 over weeks 22, 23 and 24 of the double‐blind, placebo‐controlled phase. Analyzed with a repeated measures logistic regression model employing a similar contrast as for the primary efficacy analysis.; 5. Sustainability of therapeutic response, defined as the percentage of participants with improvement in MG‐ADL total score of = 2 points at Week 2 sustained through Week 24, with no more than 2 excursions allowed at Weeks 3 through 23 (excursions defined as loss of improvement in MG‐ADL score of = 2 points). A participant with a missing assessment at a time point will be considered a nonresponder at that time point. Analyzed by Cochran‐Mantel‐Haenszel test controlling for the baseline MG‐ADL total score randomization strata (=9, >9), autoantibody status, and region. Timepoint(s) of evaluation of this end point: ‐ QMG score over Weeks 22 and 24.; ‐ MG‐ADL total score over weeks 22, 23 and 24; ‐ Loading dose response at Week 1 and/or Week 2.; ‐ Symptom remission over weeks 22, 23 and 24; ‐ Sustainability of therapeutic response Week 2 through Week 24 INCLUSION CRITERIA: RANDOMIZED PHASE: 1. =18 years of age at the time of consent. 2. Diagnosis of MG with generalized muscle weakness meeting the clinical criteria for gMG as defined by the MGFA Clinical Classification Class II a/b, III a/b, or IVa/b at screening. 3. MG‐ADL score of =6 at screening and baseline. 4. Has suboptimal response to current stable therapy for gMG according to the investigator. Stable therapy is defined in the protocol. 5. A participant using herbal, naturopathic, traditional Chinese remedies, ayurvedic or nutritional supplements, or medical marijuana is eligible if the use is acceptable to the investigator. 6. Participants who have undergone splenectomy must be at least 3 months post resection prior to screening and must be vaccinated as per the United States Center for Disease Control and Prevention annual Recommended Immunization Schedule for Adults, United States. OR must be vaccinated as per country‐specific guidelines or local