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A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Primary Purpose

Myasthenia Gravis

Status

Recruiting

Phase

Phase 3

Locations

International

Study Type

Interventional

Intervention

Nipocalimab

Placebo

About this trial

This is an interventional treatment trial for Myasthenia Gravis

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

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

Sites / Locations

Neuromuscular Research Center and ClinicRecruiting
HonorHealth NeurologyRecruiting
University of Southern CaliforniaRecruiting
Stanford UniversityRecruiting
Care Access ResearchRecruiting
University of Colorado - Anschutz Medical CampusRecruiting
Yale New Haven HospitalRecruiting
FM Clinical Research, LLC South Florida Neurology Associates, P. A.Recruiting
University of Florida Health Jacksonville
Medsol Clinical Research Center IncRecruiting
University of South FloridaRecruiting
Augusta UniversityRecruiting
University of Kansas Medical CenterRecruiting
St. Elizabeth Medical CenterRecruiting
Lahey Hospital & Medical CenterRecruiting
Washington University School of MedicineRecruiting
Duke University School of MedicineRecruiting
University of CincinnatiRecruiting
Cleveland ClinicRecruiting
The Ohio State UniversityRecruiting
Medical University of South CarolinaRecruiting
Wesley NeurologyRecruiting
UT Southwestern Medical CenterRecruiting
University of VermontRecruiting
Melbourne Neurology GroupRecruiting
Gold Coast University HospitalRecruiting
ULB Hôpital ErasmeRecruiting
AZ Sint-Jan Brugge-Oostende AVRecruiting
Cliniques Universitaires Saint LucRecruiting
AZ Sint-LucasRecruiting
University Hospitals LeuvenRecruiting
The Ottawa Hospital Research InstituteRecruiting
Toronto General HospitalRecruiting
McGill UniversityRecruiting
Beijing Tiantan Hospital, Capital Medical UniversityRecruiting
Xuanwu Hospital, Capital Medical UniversityRecruiting
Beijing HospitalRecruiting
The First Bethune Hospital of Jilin UniversityRecruiting
Central South University Xiangya Hospital The First Affiliated Hospital of Hunan Medical CollegeRecruiting
West China Hospital of Sichuan UniversityRecruiting
Fujian Medical University Union HospitalRecruiting
The First Affiliated Hospital of Guangzhou University of Traditional Chinese MedicineRecruiting
Sir Run Run Shaw Hospital, Zhejiang University School of MedicineRecruiting
Qianfoshan hospital of Shandong ProvinceRecruiting
Qilu Hospital of Shandong UniversityRecruiting
Huashan Hospital Fudan UniversityRecruiting
Tianjin Medical University General HospitalRecruiting
The Second Affiliated Hospital of Air Force Medical University - Tangdu HospitalRecruiting
Neurologie a rehabilitace SkopalíkovaRecruiting
Fakultni nemocnice BrnoRecruiting
Vseobecna Fakultní NemocniceRecruiting
Aalborg University HospitalRecruiting
RigshospitaletRecruiting
Hopital Pierre WertheimerRecruiting
CHU GrenobleRecruiting
Hopital de la Pitie SalpetriereRecruiting
Hopital PASTEURRecruiting
NeuroCure Clinical Research CenterRecruiting
Universitätsmedizin GöttingenRecruiting
Universitaetsklinikum LeipzigRecruiting
Universitätsklinikum Schleswig Holstein Campus LübeckRecruiting
Universitatsklinikum UlmRecruiting
DKD HELIOS Klinik Wiesbaden, Fachbereich NeurologieRecruiting
U.O.P.I. di PsichiatriaRecruiting
Fondazione Istituto G. GiglioRecruiting
Istituto Neurologico Carlo BestaRecruiting
Azienda Ospedaliera Univ.- Università Degli studi della Campania - Luigi VanvitelliRecruiting
IRCCS C. Mondino, Istituto Neurologico Nazionale, FondazioneRecruiting
Azienda ospedaliera Sant'Andrea di Roma- Università di Roma La SapienzaRecruiting
Policlinico Universitario Agostino GemelliRecruiting
Chiba University HospitalRecruiting
General Hanamaki HospitalRecruiting
Hiroshima University HospitalRecruiting
Teikyo University HospitalRecruiting
St.Marianna University HospitalRecruiting
Kagawa University HospitalRecruiting
Kumamoto University HospitalRecruiting
Iwate Medical University HospitalRecruiting
National Hospital Organization Nagoya Medical CenterRecruiting
Niigata City General HospitalRecruiting
Hyogo College of Medicine HospitalRecruiting
Sapporo Medical University HospitalRecruiting
Hokkaido Medical CenterRecruiting
National Hospital Organization Sendai Medical CenterRecruiting
Tokushima University HospitalRecruiting
Tokyo Medical University HospitalRecruiting
Pusan National University HospitalRecruiting
Kyungpook National University Chilgok HospitalRecruiting
Kyungpook National University HospitalRecruiting
Severance Hospital, Yonsei University Health SystemRecruiting
iBiomed Research Unit
Consultorio Dr. Miguel CortesRecruiting
Hospital Civil de Guadalajara Fray Antonio AlcaldeRecruiting
Neurocentrum Bydgoszcz Sp Z O ORecruiting
NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'Recruiting
Centrum Neurologii Klinicznej, Krakowska Akademia NeurologiiRecruiting
Prywatny Gabinet LekarskiRecruiting
Centrum Medyczne NeuroProtectRecruiting
Hosp. Gral. Univ. de AlicanteRecruiting
Hosp. de La Santa Creu I Sant PauRecruiting
Hosp. Univ. Vall D HebronRecruiting
Hosp. Clinic I Provincial de BarcelonaRecruiting
Hosp. Univ. de BasurtoRecruiting
Hosp. Virgen MacarenaRecruiting
Hosp. Virgen Del RocioRecruiting
Hosp. Univ. I Politecni La FeRecruiting
Karlstad Central HospitalRecruiting
Karolinska Universitetssjukhuset SolnaRecruiting
China Medical University HospitalRecruiting
Shin Kong Wu Ho Su Memorial HospitalRecruiting
Taipei Veterans General HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Nipocalimab

Placebo

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Average Change from Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score

Average change from baseline in MG-ADL score over Weeks 22, 23 and 24 of the double-blind placebo-controlled phase will be reported. Averaging over multiple time points (Weeks 22, 23 and 24) will be done to get a single measure. The MG-ADL provides a rapid assessment of the participant's MG symptom severity. 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) are rated on a 4-point scale: 0 (no impairment) to 3 (severe impairment). The total score will be sum of eight function scores and can range from 0 to 24. A higher score indicates greater symptom severity.

Secondary Outcome Measures

Average Change in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24 of the Double-blind Placebo-controlled Phase

Average change in QMG score over Weeks 22 and 24 of the double-blind placebo-controlled phase will be reported. The QMG test is a standardized quantitative strength assessment comprising 13 components. The quantitative results of each strength component are mapped to the following 4-point scale: 0 equals to (=) none, 1 = mild, 2 = moderate and 3 = severe. The total score will be sum of 13 components scores and can range from 0 to 39. A higher score indicates greater weakness.

Percentage of Participants whose Average MG-ADL Total Score Over Weeks 22, 23, and 24 is at least a 2-Point Improvement from Baseline of the Double-blind Placebo-controlled Phase

Percentage of participants whose average MG-ADL total score over Weeks 22, 23, and 24 is at least a 2-point improvement from baseline of the double-blind placebo-controlled phase will be reported.

Percentage of Participants with Improvement in MG-ADL Total Score Greater Than Or Equal to (>=) 2 Points at Week 1 and/or Week 2 of the Double-blind Placebo-controlled Phase

Percentage of participants with improvement in MG-ADL total score >= 2 points at Week 1 and/or Week 2 of the double-blind placebo-controlled phase will be reported.

Percentage of Participants with Improvement in MG-ADL Total Score >= 2 Points at Week 4 through Week 24 of the Double-blind Placebo-controlled Phase with No More Than 2 Non-consecutive Excursions Allowed Between Weeks 6 through Week 23

Percentage of participants with improvement in MG-ADL total score >= 2 points at Week 4 through Week 24 of the double-blind placebo-controlled phase with no more than 2 non-consecutive excursions allowed between Weeks 6 through Week 23 (excursion is defined as loss of improvement in MG-ADL score >= 2 points from baseline) will be reported.

Percentage of Participants whose Average Improvement in MG-ADL Total Score Over Weeks 22, 23, and 24 of the Double-blind, Placebo-controlled Phase is at Least a 50% Improvement from Baseline

Percentage of participants whose average improvement in MG-ADL total score over Weeks 22, 23, and 24 of the double-blind, placebo-controlled phase is at least a 50% improvement from baseline will be reported.

Percentage of Participants with Adverse Events (AEs)

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Percentage of Participants with Serious Adverse Events (SAEs)

A SAE is any untoward medical occurrence that at any dose: results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; is a suspected transmission of any infectious agent via a medicinal product; is medically important.

Percentage of Participants with Adverse Events of Special Interest (AESIs)

Percentage of participants with AESIs will be reported. Treatment-emergent AEs associated with the following situations are considered as AESI: 1) severe or medically significant or immediately life-threatening infections requiring intravenous (IV) anti-infective or operative/invasive intervention or requiring hospitalization or prolongation of existing hospitalization; 2) hypoalbuminemia with albumin less than (<) 20 grams per liter (g/L). Treatment-emergent AEs are defined as AEs with onset or worsening on or after date of first dose of study treatment.

Percentage of Participants with Change in Vital Signs

Percentage of participants with change in vital signs (temperature, blood pressure and heart rate) will be reported.

Percentage of Participants with Change in Clinical Laboratory Values

Percentage of participants with change in clinical laboratory (serum chemistry, hematology, lipid profiles and urinalysis) values will be reported.

Percentage of Participants with Change in Columbia-Suicide Severity Rating Scale (C-SSRS) Score

Percentage of participants with change in C-SSRS scale score will be reported. C-SSRS is semi structured clinician-administered questionnaire designed to solicit the occurrence, severity, and frequency of suicide-related ideation and behaviors. Total score ranges from 1 to 10. Higher scores indicate greater severity.

Percentage of Participants with Improvement in QMG Score of >= 3 Points from Baseline at Week 2 through Week 24 of the Double-blind Placebo-controlled Phase with No More than 2 Non-consecutive Excursions Allowed at Weeks 4 through 22

Percentage of participants with improvement in QMG score of >= 3 points from baseline at Week 2 through Week 24 of the double-blind placebo-controlled phase with no more than 2 non-consecutive excursions allowed at weeks 4 through 22 (excursions defined as loss of improvement in QMG score of >= 3 points from baseline) will be reported.

Average Change From Baseline in the Fatigue Items of the Quality of Life in Neurological Disorders Scale (Neuro-QoL Fatigue) Total Score Over Weeks 22 and 24 of Double-blind Placebo-controlled Phase

Average change from baseline in the Neuro-QoL Fatigue total score over Weeks 22 and 24 of double-blind placebo-controlled phase will be reported. Neuro-QoL fatigue is a 19-item questionnaire developed and validated for use in common neurological conditions which assesses patient-reported fatigue and associated impact on physical, mental, and social activities during the past 7 days. Each item included in the Neuro-QoL Fatigue questionnaire is graded on a 5-point Likert-type scale (1=Never; 2=Rarely; 3=Sometimes; 4=Often; 5=Always). The total scores are calculated by summing 19 items score and can range from 19-95. Higher score reflects more fatigue.

Average Change from Baseline in the Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-Qol15r) Score Over Weeks 22 And 24 of the Double-blind Placebo-controlled Phase

Average change from baseline in the MG-QoL15r score over Weeks 22 and 24 of the double-blind placebo-controlled phase will be reported. The MG-QoL15r is a participant-reported outcome instrument that measures MG-specific health-related quality of life. The MG-QoL15r contains 15 items that evaluate patients' experience related to Myasthenia Gravis over the "past few weeks" on a 3-point Likert-type scale (0=Not at all; 1=Somewhat; 2=Very much). The total score of the MG-QoL15r can be calculated by summing 15 items score and can range from 0 to 30. A higher score indicates poorer health related quality of life.

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 of the Double-blind Placebo-controlled Phase

Change from baseline in the VAS score of EQ-5D-5L scale over 24 weeks of the double-blind placebo-controlled phase will be reported. EQ-5D-5L is a 2-part instrument for use as a measure of health outcome, designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ VAS. The EQ VAS self-rating records the respondent's own assessment of his or her overall health status at the time of completion, on a scale of 0 (worst imaginable health state) to 100 (best imaginable health state). Positive change in score indicates improvement.

Change from Baseline in the Health Status Index of the EQ-5D-5L Scale Over 24 Weeks of the Double-blind Placebo-controlled Phase

Change from baseline in health status index of EQ-5D-5L scale over 24 weeks of double-blind placebo-controlled phase will be reported. EQ-5D-5L is standardized instrument for use as measure of health outcome, primarily designed for self-completion by respondents. It consists of EQ-5D-5L descriptive system and EQ-VAS. EQ-5D-5L descriptive system comprises following 5 dimensions: Mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each of 5 dimensions is divided into 5 levels of perceived problems (1 indicating no problem, 2 indicating slight problems, 3 indicating moderate problems, 4 indicating severe problems, 5 indicating extreme problems). Participant selects an answer for each of 5 dimensions considering response that best matches his or her health "today". The responses to 5 dimensions are used to compute a single score ranging from zero (0.0- worst health state) to 1 (1.0- better health state) representing the general health status of the individual.

Serum Nipocalimab Concentrations Over Time

Serum nipocalimab concentrations over time will be reported.

Number of Participants with Antibodies to Nipocalimab (Anti-Drug Antibodies [ADAs] and Neutralizing Antibodies [NAbs])

Number of participants with antibodies to nipocalimab (ADAs and NAbs) will be reported.

Percentage of Participants with MG-ADL Score of 0 or 1 Over Time in the Double-blind, Placebo-controlled Phase

Percentage of participants with MG-ADL score of 0 or 1 over time in the double-blind, placebo-controlled phase will be reported.

Percentage of Participants with MG-ADL Score of 0 or 1 at Any Time During the Double-blind, Placebo-controlled Phase

Percentage of participants with MG-ADL score of 0 or 1 at any time during the double-blind, placebo-controlled phase will be reported.

Percentage of Participants with MG-ADL Score of 0 or 1 at 50% of Timepoints During the Double-blind, Placebo-controlled Phase

Percentage of participants with MG-ADL score of 0 or 1 at 50% of timepoints during the double-blind, placebo-controlled phase will be reported.

Percentage of Participants with MG-ADL Score of 0 or 1 at 75% of Timepoints During the Double-blind, Placebo-controlled Phase

Percentage of participants with MG-ADL score of 0 or 1 at 75% of timepoints during the double-blind, placebo-controlled phase will be reported.

Change in Total Serum Immunoglobulin G (IgG) Concentrations

Change in total serum IgG concentrations will be reported.

Change in Levels of Autoantibodies Associated with Generalized Myasthenia Gravis (gMG)

Change in levels of autoantibodies associated with gMG will be reported.

Change from Baseline in MG-ADL Score as a Function of IgG

Change from baseline in MG-ADL score as a function of IgG will be reported.

Change from Baseline in QMG Score as a Function of IgG

Change from baseline in QMG score as a function of IgG will be reported.

Change From Baseline in MG-ADL Score as a Response to Percent Change in Autoantibody Levels, in Seropositive Participants Treated with Nipocalimab

Change from baseline in MG-ADL as a response to percent change in autoantibody levels, in seropositive participants (anti-acetylcholine receptor [anti-AChR], anti-muscle-specific kinase [anti-MuSK], anti-lipoprotein-related protein receptor 4 [anti-LRP4]) treated with nipocalimab will be reported.

Change From Baseline in QMG Score as a Response to Percent Change in Autoantibody Levels, in Seropositive Participants Treated with Nipocalimab

Change from baseline in QMG score as a response to percent change in autoantibody levels, in seropositive participants (anti-AChR, anti-MuSK, anti-LRP4) treated with nipocalimab will be reported.

Full Information

NCT ID

NCT04951622

First Posted

June 30, 2021

Last Updated

October 10, 2023

Sponsor

Janssen Research & Development, LLC

1. Study Identification

Unique Protocol Identification Number

NCT04951622

Brief Title

A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2023

Overall Recruitment Status

Recruiting

Study Start Date

July 15, 2021 (Actual)

Primary Completion Date

November 1, 2023 (Anticipated)

Study Completion Date

April 17, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Janssen Research & Development, LLC

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Myasthenia Gravis

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

198 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nipocalimab

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Nipocalimab

Other Intervention Name(s)

JNJ-80202135, M281

Intervention Description

Nipocalimab will be administered as an IV infusion.

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

Matching placebo will be administered as an IV infusion.

Primary Outcome Measure Information:

Title

Average Change from Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Score

Description

Time Frame

Baseline up to Week 24

Secondary Outcome Measure Information:

Title

Average Change in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24 of the Double-blind Placebo-controlled Phase

Description

Time Frame

Up to Weeks 22 and 24

Title

Percentage of Participants whose Average MG-ADL Total Score Over Weeks 22, 23, and 24 is at least a 2-Point Improvement from Baseline of the Double-blind Placebo-controlled Phase

Description

Percentage of participants whose average MG-ADL total score over Weeks 22, 23, and 24 is at least a 2-point improvement from baseline of the double-blind placebo-controlled phase will be reported.

Time Frame

Baseline up to Weeks 22, 23 and 24

Title

Percentage of Participants with Improvement in MG-ADL Total Score Greater Than Or Equal to (>=) 2 Points at Week 1 and/or Week 2 of the Double-blind Placebo-controlled Phase

Description

Percentage of participants with improvement in MG-ADL total score >= 2 points at Week 1 and/or Week 2 of the double-blind placebo-controlled phase will be reported.

Time Frame

Weeks 1 and 2

Title

Description

Time Frame

Week 4 up to Week 24

Title

Percentage of Participants whose Average Improvement in MG-ADL Total Score Over Weeks 22, 23, and 24 of the Double-blind, Placebo-controlled Phase is at Least a 50% Improvement from Baseline

Description

Time Frame

Baseline, Weeks 22, 23 and 24

Title

Percentage of Participants with Adverse Events (AEs)

Description

An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study.

Time Frame