A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Myasthenia Gravis Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04951622
• Other study ID #: CR109046
• Secondary ID: 2020-005732-29MO
• Status: Recruiting
• Phase: Phase 3
• Start date: July 15, 2021
• Est. completion date: April 17, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: Study Contact
• Phone: 844-434-4210
• Email: Participate-In-This-Study[@]its.jnj.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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 information / eligibility

• Status: Recruiting
• Enrollment: 198
• Est. completion date: April 17, 2026
• Est. primary completion date: November 17, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Muscle Weakness
• Myasthenia Gravis

Intervention

Drug:
• Nipocalimab
Nipocalimab will be administered as an IV infusion.
• Placebo
Matching placebo will be administered as an IV infusion.

Locations

Country	Name	City	State
Australia	Melbourne Neurology Group	North Melbourne
Australia	Gold Coast University Hospital	Southport
Belgium	ULB Hôpital Erasme	Anderlecht
Belgium	AZ Sint-Jan Brugge-Oostende AV	Brugge
Belgium	Cliniques Universitaires Saint Luc	Brussels
Belgium	AZ Sint-Lucas	Gent
Belgium	University Hospitals Leuven	Leuven
Canada	McGill University	Montreal	Quebec
Canada	The Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Toronto General Hospital	Toronto	Ontario
China	Beijing Hospital	Beijing
China	Beijing Tiantan Hospital, Capital Medical University	Beijing
China	Xuanwu Hospital ,Capital Medical University	Beijing
China	The First Bethune Hospital of Jilin University	Changchun
China	Central South University Xiangya Hospital The First Affiliated Hospital of Hunan Medical College	Changsha
China	West China Hospital of Sichuan University	Chengdu
China	Fujian Medical University Union Hospital	Fuzhou
China	The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine	Guangzhou
China	Sir Run Run Shaw Hospital, Zhejiang University School of Medicine	Hangzhou
China	Qianfoshan hospital of Shandong Province	Jinan
China	Qilu Hospital of Shandong University	Jinan
China	Huashan Hospital Fudan University	Shanghai
China	Tianjin Medical University General Hospital	Tianjin
China	The Second Affiliated Hospital of Air Force Medical University - Tangdu Hospital	Xi'An
Czechia	Fakultni nemocnice Brno	Brno
Czechia	Neurologie a rehabilitace Skopalíkova	Brno
Czechia	Vseobecna Fakultní Nemocnice	Praha
Denmark	Aalborg University Hospital	Aalborg
Denmark	Rigshospitalet	København Ø
France	Hopital Pierre Wertheimer	Bron
France	CHU Grenoble	Grenoble
France	Hopital de la Pitie Salpetriere	Paris
France	Hopital PASTEUR	Provence-Alpes-Côte d'Azur
Germany	NeuroCure Clinical Research Center	Berlin
Germany	Universitatsmedizin Gottingen	Göttingen
Germany	Universitaetsklinikum Leipzig	Leipzig
Germany	Universitatsklinikum Schleswig Holstein Campus Lubeck	Lübeck
Germany	Universitatsklinikum Ulm	Ulm
Germany	DKD HELIOS Klinik Wiesbaden, Fachbereich Neurologie	Wiesbaden
Italy	U.O.P.I. di Psichiatria	Catania
Italy	Fondazione Istituto G. Giglio	Cefalu
Italy	Istituto Neurologico Carlo Besta	Milano
Italy	Azienda Ospedaliera Univ.- Università Degli studi della Campania - Luigi Vanvitelli	Napoli
Italy	IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione	Pavia
Italy	Azienda ospedaliera Sant'Andrea di Roma- Università di Roma La Sapienza	Roma
Italy	Policlinico Universitario Agostino Gemelli	Roma
Japan	Chiba University Hospital	Chiba
Japan	General Hanamaki Hospital	Hanamaki
Japan	Hiroshima University Hospital	Hiroshima shi
Japan	Teikyo University Hospital	Itabashi Ku
Japan	St Marianna University Hospital	Kawasaki Shi
Japan	Kagawa University Hospital	Kita-Gun
Japan	Kumamoto University Hospital	Kumamoto
Japan	Iwate Medical University Hospital	Morioka-shi
Japan	National Hospital Organization Nagoya Medical Center	Nagoya-shi
Japan	Niigata City General Hospital	Niigata
Japan	Hyogo College of Medicine Hospital	Nishinomiya-Shi
Japan	Hokkaido Medical Center	Sapporo
Japan	Sapporo Medical University Hospital	Sapporo
Japan	National Hospital Organization Sendai Medical Center	Sendai-City
Japan	Tokushima University Hospital	Tokushima
Japan	Tokyo Medical University Hospital	Tokyo
Korea, Republic of	Pusan National University Hospital	Busan
Korea, Republic of	Kyungpook National University Chilgok Hospital	Daegu
Korea, Republic of	Kyungpook National University Hospital	Daegu
Korea, Republic of	Severance Hospital Yonsei University Health System	Seoul
Mexico	iBiomed Research Unit	Aguascalientes
Mexico	Consultorio Dr. Miguel Cortes	Cuernavaca
Mexico	Hospital Civil de Guadalajara Fray Antonio Alcalde	Guadalajara
Poland	Neurocentrum Bydgoszcz Sp Z O O	Bydgoszcz
Poland	NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'	Katowice
Poland	Centrum Neurologii Klinicznej, Krakowska Akademia Neurologii	Krakow
Poland	Prywatny Gabinet Lekarski	Lublin
Poland	Centrum Medyczne NeuroProtect	Warsaw
Spain	Hosp. Gral. Univ. de Alicante	Alicante
Spain	Hosp Clinic de Barcelona	Barcelona
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. Univ. de Basurto	Bilbao
Spain	Hosp. Virgen Del Rocio	Sevilla
Spain	Hosp. Virgen Macarena	Sevilla
Spain	Hosp. Univ. I Politecni La Fe	Valencia
Sweden	Karlstad Central Hospital	Karlstad
Sweden	Karolinska Universitetssjukhuset Solna	Stockholm
Taiwan	China Medical University Hospital	Taichung
Taiwan	Shin Kong Wu Ho Su Memorial Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
United States	Augusta University	Augusta	Georgia
United States	University of Colorado Anschutz Medical Campus	Aurora	Colorado
United States	FM Clinical Research, LLC South Florida Neurology Associates, P. A.	Boca Raton	Florida
United States	St. Elizabeth Medical Center	Boston	Massachusetts
United States	Lahey Hospital & Medical Center	Burlington	Massachusetts
United States	University of Vermont	Burlington	Vermont
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Cincinnati	Cincinnati	Ohio
United States	Cleveland Clinic	Cleveland	Ohio
United States	The Ohio State University	Columbus	Ohio
United States	Wesley Neurology	Cordova	Tennessee
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Duke University School of Medicine	Durham	North Carolina
United States	University of Florida Health Jacksonville	Jacksonville	Florida
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	University of Southern California	Los Angeles	California
United States	Yale New Haven Hospital	New Haven	Connecticut
United States	Stanford University	Palo Alto	California
United States	Neuromuscular Research Center and Clinic	Paradise Valley	Arizona
United States	Care Access Research	Pasadena	California
United States	Medsol Clinical Research Center Inc	Port Charlotte	Florida
United States	Washington University School Of Medicine	Saint Louis	Missouri
United States	HonorHealth Neurology	Scottsdale	Arizona
United States	University of South Florida	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  China,  Czechia,  Denmark,  France,  Germany,  Italy,  Japan,  Korea, Republic of,  Mexico,  Poland,  Spain,  Sweden,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline up to Week 24
Secondary	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.	Up to Weeks 22 and 24
Secondary	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.	Baseline up to Weeks 22, 23 and 24
Secondary	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.	Weeks 1 and 2
Secondary	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.	Week 4 up to Week 24
Secondary	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.	Baseline, Weeks 22, 23 and 24
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Up to Week 24 of double-blind placebo-controlled phase and up to extension Week 24 of open-label extension phase (up to Week 48)
Secondary	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.	Week 2 up to Week 24
Secondary	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.	Baseline up to Weeks 22 and 24
Secondary	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.	Baseline up to Weeks 22 and 24
Secondary	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.	Baseline up to 24 weeks
Secondary	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.	Baseline up to 24 weeks
Secondary	Serum Nipocalimab Concentrations Over Time	Serum nipocalimab concentrations over time will be reported.	Up to 4 years and 8 months
Secondary	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.	Up to 4 years and 8 months
Secondary	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.	Up to Week 24
Secondary	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.	Up to Week 24
Secondary	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.	Up to Week 24
Secondary	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.	Up to Week 24
Secondary	Change in Total Serum Immunoglobulin G (IgG) Concentrations	Change in total serum IgG concentrations will be reported.	Up to 4 years and 8 months
Secondary	Change in Levels of Autoantibodies Associated with Generalized Myasthenia Gravis (gMG)	Change in levels of autoantibodies associated with gMG will be reported.	Up to 4 years and 8 months
Secondary	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.	Baseline up to 4 years and 8 months
Secondary	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.	Baseline up to 4 years and 8 months
Secondary	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.	Baseline up to 4 years and 8 months
Secondary	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.	Baseline up to 4 years and 8 months