RecruitingInterventionalPhase 3

Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

NCT ID: NCT04951622Sponsor: Janssen Research & Development, LLCLast updated: 2026-03-03

Summary

The purpose of this study is to evaluate the efficacy and safety of nipocalimab compared to placebo in participants with generalized myasthenia gravis (gMG). The purpose of the subcutaneous substudy is to evaluate how well it works in the body (pharmacodynamic \[PD\]) when given as an injection under the skin (subcutaneous) compared to when given through a vein (intravenous) in participants with gMG.

Arms & interventions

DrugNipocalimab
Nipocalimab will be administered as an IV infusion.
DrugPlacebo
Matching placebo will be administered as an IV infusion.
DrugNipocalimab SC-LIV
Nipocalimab will be administered subcutaneously.

Outcome measures

Primary

Double-blind (DB) Phase: Average Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24
Average change from baseline over multiple timepoints (Weeks 22, 23, and 24) was reported in this outcome measure. The MG-ADL provided a rapid assessment of the participant's MG symptom severity of eight functions (talking, chewing, swallowing, breathing, impairment of ability to brush teeth or comb hair, impairment of ability to arise from a chair, double vision, eyelid droop) rated on a 4-point scale ranging from 0 (normal) to 3 (severe). MG-ADL total score was sum of 8 individual items, which ranging from 0 to 24. A higher score indicated greater symptom severity. Baseline was defined as the average of the screening and Day 1 total scores.
Time frame: Baseline, Weeks 22, 23, and 24
Sub Study: Percent Change in Anti-AChR Autoantibody Titer From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)
Time frame: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)
Sub Study: Percent Change in Total IgG Levels From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)
Time frame: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)

Secondary

DB Phase: Average Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24
Time frame: Baseline, Weeks 22, and 24
DB Phase: Percentage of Participants Who Had Achieved at Least a 2-point Average Improvement From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24
Time frame: Weeks 22, 23, and 24
DB Phase: Percentage of Participants Who Had Achieved an Improvement of Greater Than or Equal to (>=) 2 Points in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score at Week 1 and/or Week 2
Time frame: Weeks 1 and 2
DB Phase: Percentage of Participants Who Had an Improvement of >= 2 Points in the MG-ADL Total Score From Week 4 Through Week 24 With no More Than 2 Non-consecutive Excursions Allowed Between Weeks 6 Through 23
Time frame: From Week 4 up to Week 24
DB Phase: Percentage of Participants Who Had Achieved at Least a 50 Percent (%) Average Improvement From Baseline in the Myasthenia Gravis - Activities of Daily Living (MG-ADL) Total Score Over Weeks 22, 23, and 24
Time frame: Weeks 22, 23, and 24
Percentage of Participants With Treatment-emergent Adverse Events (TEAEs)
Time frame: From start of treatment (DB phase Day 1) up to 4 years 9 months
Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs)
Time frame: From start of treatment (DB phase Day 1) up to 4 years 9 months
Percentage of Participants With AEs of Special Interest (AESIs)
Time frame: From start of treatment (DB phase Day 1) up to 4 years 9 months
Number of Participants With Change in Vital Signs
Time frame: From start of treatment (DB phase Day 1) up to 4 years 9 months
Number of Participants With Change in Clinical Laboratory Values
Time frame: From start of treatment (DB phase Day 1) up to 4 years 9 months
Number of Participants With Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) Score
Time frame: From start of treatment (Day 1) up to 4 years 9 months
DB Phase: Percentage of Participants Who Had an Improvement of >= 3 Points in Quantitative Myasthenia Gravis (QMG) Score From Baseline, at Week 2 Through Week 24, With No More Than 2 Non-consecutive Excursions Allowed Between at Weeks 4 Through Week 22
Time frame: Baseline, Week 2 up to Week 24
DB Phase: Average Change From Baseline in the Fatigue Items of the Quality of Life in Neurological Disorders (Neuro-QoL) Fatigue Scale Total Score Over Weeks 22 and 24
Time frame: Baseline up to Weeks 22, and 24
DB Phase: Average Change From Baseline in the Revised Myasthenia Gravis Quality of Life (Revised) Instrument (MG-Qol15r) Score Over Weeks 22 And 24
Time frame: Baseline up to Weeks 22, and 24
DB Phase: Change From Baseline in the Visual Analog Scale (VAS) Score of European Quality of Life (EuroQol) 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks
Time frame: Baseline up to Week 24
DB Phase: Change From Baseline in the Health Status Index of the EuroQol 5-Dimension 5-Level (EQ-5D-5L) Scale Over 24 Weeks
Time frame: Baseline up to Week 24
DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 Over Time
Time frame: Baseline up to Week 24
DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at Any Time
Time frame: Baseline up to Week 24
DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 50% of Timepoints
Time frame: Baseline up to Week 24
DB Phase: Percentage of Participants With Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score of 0 or 1 at 75% of Timepoints
Time frame: Baseline up to Week 24
Serum Concentrations of Nipocalimab Over Time
Time frame: DB Phase: Predose and 45 minutes post-dose on Day 1, Weeks 2, 4, 8, 12,16, 20, 24;OL Phase: Predose on Day 1, Weeks 8, 16, 24, 36, 48, 60, 72, 84, and 96
Number of Participants With Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])
Time frame: From start of treatment (Day 1) up to 4 years 9 months
Percent Change From Baseline in Total Serum Immunoglobulin G (IgG) Concentrations
Time frame: Baseline up to 4 years 9 months
Change From Baseline in Levels of Autoantibodies Associated With Generalized Myasthenia Gravis (gMG)
Time frame: Baseline up to 4 years 9 months
Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Function of IgG
Time frame: Baseline up to 4 years 9 months
Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score as a Function of Immunoglobulin G (IgG)
Time frame: Baseline up to 4 years 9 months
Change From Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab
Time frame: Baseline up to 4 years 9 months
Change From Baseline in QMG Score as a Response to Percent Change in Autoantibody Levels in Seropositive Participants Treated With Nipocalimab
Time frame: Baseline up to 4 years 9 months
Sub Study: Number of Participants With Treatment-Emergent AEs
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Number of Participants With Abnormalities in Vital Signs
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Number of Participants With Abnormalities in Physical Examinations
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Number of Participants With Abnormalities in Laboratory Parameters
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Numeric Pain Rating Scale (NPRS) Assessment With SC Use of Nipocalimab
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Number of Participants With Injection Site-Reactions
Time frame: Up to SC Week 8 (Day 57)
Sub Study: Change From Baseline in MG-ADL Clinician-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in QMG Clinician-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in Myasthenia Gravis Foundation of America (MGFA) Clinician-Reported Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in C-SSRS Clinician-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in Neuro-QoL Participant-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in Patient Global Impression of Severity (PGIS) Scale Score up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in Patient Global Impression of Change (PGIC) Scale Score up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in MG-QoL Participant-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Change From Baseline in EQ-5D-5L Participant-Reported Outcome Measures up to Week 8 (Day 57)
Time frame: From baseline (pre-first nipocalimab dose on Day 1) up to Week 8 (Day 57)
Sub Study: Percent Change in Total IgG Levels From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)
Time frame: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)
Sub Study: Percent Change in Anti-AChR Autoantibody Titer From Pre-first Nipocalimab Dose on Day 1 up to Week 8 (Day 57)
Time frame: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No

Inclusion Criteria: * Diagnosis of myasthenia gravis (MG) with generalized muscle weakness meeting the clinical criteria for generalized myasthenia gravis (gMG) as defined by the Myasthenia Gravis Foundation of America (MGFA) Clinical Classification Class II a/b, III a/b, or IVa/b at screening * Myasthenia Gravis - Activities of Daily Living (MG-ADL) score of greater than or equal to (\>=) 6 at screening and baseline * Has sufficient venous access to allow drug administration by infusion and blood sampling as per the protocol * A woman of childbearing potential must have a negative highly sensitive serum (beta-human chorionic gonadotropin \[beta-hCG\]) at screening and a negative urine pregnancy test at Day 1 prior to administration of study intervention * A male participant must agree not to donate sperm for the purpose of reproduction during the study and for a minimum 90 days after receiving the last administration of study intervention * For the SC Substudy (Cohort 1 and Cohort 2): Has reasonable abdominal skin area for SC administration * For the SC Substudy (Cohort 1 and Cohort 2): Participants must be willing to comply with maintaining their stable dose of corticosteroids and/or immunosuppressants for the initial 8 weeks of the SC substudy, that is, through the SC Week 8 visit Exclusion Criteria: * Has any confirmed or suspected clinical immunodeficiency syndrome not related to treatment of his/her gMG, or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant * Has MGFA Class I disease or presence of MG crisis (MGFA Class V) at screening, history of MG crisis within 1 month of screening, or fixed weakness (and/or 'burnt out' MG) * Has had a thymectomy within 12 months prior to screening, or thymectomy is planned during the study * Has known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients * Has experienced myocardial infarction, unstable ischemic heart disease, or stroke within 12 weeks of screening * For the SC Substudy (Cohort 1): Participants who have undergone a recent tapering of their concomitant MG medication in the OLE * For the SC Substudy (Cohort 1): Participants deteriorating during the OLE in the month prior to SC Dose 1 of the SC substudy such that they meet the criteria for clinical deterioration * For the SC Substudy (Cohort 2): History of an unprovoked pulmonary embolism within 1 year prior to screening or history of recurrent deep vein thrombosis (DVT)

Study locations (24)

Neuromuscular Research Center and Clinic

Paradise Valley, Arizona, 85028

Recruiting

HonorHealth Neurology

Scottsdale, Arizona, 85251

Completed

University of Southern California

Los Angeles, California, 90033

Completed

Stanford University

Palo Alto, California, 94304

Completed

Care Access Research

Pasadena, California, 91101

Recruiting

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045

Recruiting

Yale New Haven Hospital

New Haven, Connecticut, 06519

Recruiting

FM Clinical Research, LLC South Florida Neurology Associates, P. A.

Boca Raton, Florida, 33487

Recruiting

University of Florida Health Jacksonville

Jacksonville, Florida, 32209

Completed

Medsol Clinical Research Center Inc

Port Charlotte, Florida, 33952

Recruiting

University of South Florida

Tampa, Florida, 33612

Recruiting

Augusta University

Augusta, Georgia, 30912-3125

Completed

University of Kansas Medical Center

Kansas City, Kansas, 66160

Recruiting

St. Elizabeth Medical Center

Boston, Massachusetts, 02135

Completed

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805

Completed

Washington University School Of Medicine

St Louis, Missouri, 63110

Completed

Duke University School of Medicine

Durham, North Carolina, 27710

Recruiting

University of Cincinnati

Cincinnati, Ohio, 45219

Completed

Cleveland Clinic

Cleveland, Ohio, 44145

Recruiting

The Ohio State University

Columbus, Ohio, 43210

Completed

Medical University of South Carolina

Charleston, South Carolina, 29425

Recruiting

Wesley Neurology

Cordova, Tennessee, 38018

Completed

UT Southwestern Medical Center

Dallas, Texas, 75390

Completed

University of Vermont

Burlington, Vermont, 05401

Completed

References

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