A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Phase 3RecruitingNCT04951622

Janssen Research & Development, LLC199 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

199

Conditions

Myasthenia Gravis

Interventions

NipocalimabDRUG

Nipocalimab will be administered as an IV infusion.

PlaceboDRUG

Matching placebo will be administered as an IV infusion.

Nipocalimab SC-LIVDRUG

Nipocalimab will be administered subcutaneously.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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)

Locations (112)

Outcomes

Primary Outcomes

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 Outcomes

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

Central Contacts

Study Contact

CONTACT

844-434-4210 Participate-In-This-Study1@its.jnj.com

Data from ClinicalTrials.gov

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Neuromuscular Research Center and Clinic

Paradise Valley, Arizona, United States

RECRUITING

HonorHealth Neurology

Scottsdale, Arizona, United States

COMPLETED

University of Southern California

Los Angeles, California, United States

COMPLETED

Stanford University

Palo Alto, California, United States

COMPLETED

Care Access Research

Pasadena, California, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, United States

RECRUITING

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

Boca Raton, Florida, United States

RECRUITING

University of Florida Health Jacksonville

Jacksonville, Florida, United States

COMPLETED

Medsol Clinical Research Center Inc

Port Charlotte, Florida, United States

RECRUITING

...and 102 more locations

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)