A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis
- Registration Number
- NCT04951622
- Lead Sponsor
- Janssen Research & Development, LLC
- Brief 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).
- Detailed Description
Myasthenia gravis (MG) is a rare, heterogeneous, neuromuscular disease characterized by fluctuating, fatigable muscle weakness. MG is caused by pathogenic autoantibodies that impair cholinergic transmission in the postsynaptic membrane at the neuromuscular junction and impair or prevent muscle contraction. Nipocalimab (also referred to as JNJ-80202135 or M281) is a fully human, aglycosylated immunoglobulin (Ig)G1 monoclonal antibody (mAb) designed to selectively bind, saturate, and block the IgG binding site on the endogenous neonatal Fc receptor (FcRn). This study will consist of a screening phase (up to 4 weeks), treatment phase (a 24-week double-blind placebo-controlled phase, and an open-label extension \[OLE\] phase \[up to 2 years\]) and a follow-up safety visit (up to 8 weeks after last infusion of study intervention). Efficacy evaluations will include assessments such as Myasthenia Gravis - Activities of Daily Living (MG-ADL) score. Safety evaluations (such as adverse events, physical examination, vital signs, electrocardiogram \[ECG\], and clinical laboratory tests) will be performed. The overall duration of study will be up to 4 years and 8 months.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 219
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo Double-blind Placebo-controlled Phase: Participants will receive matching placebo of nipocalimab IV infusion q2w up to 24 weeks during double-blind placebo-controlled phase. Nipocalimab Nipocalimab Double-blind Placebo-controlled Phase: Participants will receive nipocalimab intravenous (IV) infusions once every 2 weeks (q2w) up to 24 weeks during double-blind placebo-controlled phase. Open-label Extension (OLE) Phase: Participants who complete the double-blind placebo-controlled phase will enter the OLE phase and continue to receive nipocalimab q2w IV infusion till study end.
- Primary Outcome Measures
Name Time Method 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 Baseline, 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.
- Secondary Outcome Measures
Name Time Method DB Phase: Average Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24 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 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 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 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 Weeks 22, 23, and 24 Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) From start of treatment (DB phase Day 1) up to 4 years 9 months Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) From start of treatment (DB phase Day 1) up to 4 years 9 months Percentage of Participants With AEs of Special Interest (AESIs) From start of treatment (DB phase Day 1) up to 4 years 9 months Number of Participants With Change in Vital Signs From start of treatment (DB phase Day 1) up to 4 years 9 months Number of Participants With Change in Clinical Laboratory Values 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 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 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 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 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 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 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 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 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 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 Baseline up to Week 24 Serum Concentrations of Nipocalimab Over Time 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]) From start of treatment (Day 1) up to 4 years 9 months Percent Change From Baseline in Total Serum Immunoglobulin G (IgG) Concentrations Baseline up to 4 years 9 months Change From Baseline in Levels of Autoantibodies Associated With Generalized Myasthenia Gravis (gMG) 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 Baseline up to 4 years 9 months Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score as a Function of Immunoglobulin G (IgG) 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 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 Baseline up to 4 years 9 months
Trial Locations
- Locations (111)
Neuromuscular Research Center and Clinic
🇺🇸Paradise Valley, Arizona, United States
HonorHealth Neurology
🇺🇸Scottsdale, Arizona, United States
University of Southern California
🇺🇸Los Angeles, California, United States
Stanford University
🇺🇸Palo Alto, California, United States
Care Access Research
🇺🇸Pasadena, California, United States
University of Colorado Anschutz Medical Campus
🇺🇸Aurora, Colorado, United States
Yale New Haven Hospital
🇺🇸New Haven, Connecticut, United States
FM Clinical Research, LLC South Florida Neurology Associates, P. A.
🇺🇸Boca Raton, Florida, United States
University of Florida Health Jacksonville
🇺🇸Jacksonville, Florida, United States
Medsol Clinical Research Center Inc
🇺🇸Port Charlotte, Florida, United States
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