A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

NCT04951622 | Recruiting Phase 3 Results DMC FDA Drug

• 4 other identifiers: CR109046MOM-M281-0112020-005732-292023-504152-97-00
• Study Type: interventional
• Target: 199
• Locations: 17 countries
• Sites: 112

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). 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.

Conditions

Myasthenia Gravis

Outcome Measures

Primary Outcomes (3)

• 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.

  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)

  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)

  From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)

Secondary Outcomes (45)

• 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

Study Arms (3)

Nipocalimab

EXPERIMENTAL

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 will have the option to continue to receive nipocalimab q2w IV infusion till study end or enter the nipocalimab SC substudy.

Drug: Nipocalimab

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Nipocalimab Subcutaneous (SC)

EXPERIMENTAL

OLE Phase: Participants from Cohort 1 will receive nipocalimab subcutaneous liquid in vial (SC-LIV) qw until Week 8. Participants with gMG from Cohort 2 who have not received nipocalimab previously, will receive nipocalimab SC-LIV until Week 8. Participants who complete the 8-week treatment period will have the opportunity to continue receiving nipocalimab SC-LIV qw in the Long term extension (LTE) period.

Drug: Nipocalimab SC-LIV

Interventions

Nipocalimab DRUG

Nipocalimab will be administered as an IV infusion.

Also known as: JNJ-80202135, M281

Nipocalimab

Placebo DRUG

Matching placebo will be administered as an IV infusion.

Placebo

Nipocalimab SC-LIV DRUG

Nipocalimab will be administered subcutaneously.

Nipocalimab Subcutaneous (SC)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Janssen Research & Development, LLC: lead

Study Sites (112)

Neuromuscular Research Center and Clinic

Paradise Valley, Arizona, 85028, United States

RECRUITING

HonorHealth Neurology

Scottsdale, Arizona, 85251, United States

COMPLETED

University of Southern California

Los Angeles, California, 90033, United States

COMPLETED

Stanford University

Palo Alto, California, 94304, United States

COMPLETED

Care Access Research

Pasadena, California, 91101, United States

RECRUITING

University of Colorado Anschutz Medical Campus

Aurora, Colorado, 80045, United States

RECRUITING

Yale New Haven Hospital

New Haven, Connecticut, 06519, United States

RECRUITING

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

Boca Raton, Florida, 33487, United States

RECRUITING

University of Florida Health Jacksonville

Jacksonville, Florida, 32209, United States

COMPLETED

Medsol Clinical Research Center Inc

Port Charlotte, Florida, 33952, United States

RECRUITING

University of South Florida

Tampa, Florida, 33612, United States

RECRUITING

Augusta University

Augusta, Georgia, 30912-3125, United States

COMPLETED

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

RECRUITING

St. Elizabeth Medical Center

Boston, Massachusetts, 02135, United States

COMPLETED

Lahey Hospital & Medical Center

Burlington, Massachusetts, 01805, United States

COMPLETED

Washington University School Of Medicine

St Louis, Missouri, 63110, United States

COMPLETED

Duke University School of Medicine

Durham, North Carolina, 27710, United States

RECRUITING

University of Cincinnati

Cincinnati, Ohio, 45219, United States

COMPLETED

Cleveland Clinic

Cleveland, Ohio, 44145, United States

RECRUITING

The Ohio State University

Columbus, Ohio, 43210, United States

COMPLETED

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

RECRUITING

Wesley Neurology

Cordova, Tennessee, 38018, United States

COMPLETED

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

COMPLETED

University of Vermont

Burlington, Vermont, 05401, United States

COMPLETED

Melbourne Neurology Group

North Melbourne, 3051, Australia

COMPLETED

Gold Coast University Hospital

Southport, 4215, Australia

RECRUITING

ULB Hôpital Erasme

Anderlecht, 1070, Belgium

RECRUITING

AZ Sint Jan Brugge Oostende AV

Bruges, 8000, Belgium

RECRUITING

Cliniques Universitaires Saint Luc

Brussels, 1200, Belgium

RECRUITING

AZ Sint-Lucas

Ghent, 9000, Belgium

RECRUITING

University Hospitals Leuven

Leuven, 3000, Belgium

RECRUITING

The Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

RECRUITING

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

RECRUITING

McGill University

Montreal, Quebec, H3A 2B4, Canada

COMPLETED

Beijing Tiantan Hospital, Capital Medical University

Beijing, 100050, China

RECRUITING

Xuanwu Hospital ,Capital Medical University

Beijing, 100053, China

COMPLETED

Beijing Hospital

Beijing, 100730, China

RECRUITING

The First Bethune Hospital of Jilin University

Changchun, 130021, China

RECRUITING

Xiangya Hospital Central South University

Changsha, 410008, China

RECRUITING

West China Hospital of Sichuan University

Chengdu, 610041, China

COMPLETED

Fujian Medical University Union Hospital

Fuzhou, 350001, China

COMPLETED

The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine

Guangzhou, 510405, China

RECRUITING

Sir Run Run Shaw Hospital Zhejiang University School of Medicine

Hangzhou, 310020, China

COMPLETED

Qianfoshan hospital of Shandong Province

Jinan, 250014, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, 250014, China

COMPLETED

Huashan Hospital Fudan University

Shanghai, 200040, China

RECRUITING

Tianjin Medical University General Hospital

Tianjin, 300052, China

RECRUITING

The Second Affiliated Hospital of Air Force Medical University - Tangdu Hospital

Xi'an, 710038, China

RECRUITING

Neurologie a rehabilitace Skopalíkova

Brno, 615 00, Czechia

RECRUITING

Fakultni nemocnice Brno

Brno, 625 00, Czechia

COMPLETED

Vseobecna Fakultní Nemocnice

Prague, 12808, Czechia

RECRUITING

Aalborg University Hospital

Aalborg, 9000, Denmark

COMPLETED

Rigshospitalet

København Ø, 2100, Denmark

COMPLETED

Hopital Pierre Wertheimer

Bron, 69500, France

RECRUITING

CHU Grenoble

Grenoble, 38043, France

COMPLETED

Hopital de la Pitie Salpetriere

Paris, 75013, France

RECRUITING

Hopital PASTEUR

Provence-Alpes-Côte d'Azur, 06000, France

RECRUITING

Hopital PASTEUR

Provence-Alpes-Côte d'Azur, 06000, France

COMPLETED

NeuroCure Clinical Research Center

Berlin, 10117, Germany

RECRUITING

Universitatsmedizin Gottingen

Göttingen, 37075, Germany

COMPLETED

Universitaetsklinikum Leipzig

Leipzig, 04103, Germany

COMPLETED

Universitatsklinikum Schleswig Holstein Campus Lubeck

Lübeck, 23538, Germany

COMPLETED

Universitatsklinikum Ulm

Ulm, 89081, Germany

COMPLETED

DKD HELIOS Klinik Wiesbaden, Fachbereich Neurologie

Wiesbaden, 65191, Germany

COMPLETED

U.O.P.I. di Psichiatria

Catania, 95100, Italy

COMPLETED

Fondazione Istituto G. Giglio

Cefalù, 90015, Italy

RECRUITING

Istituto Neurologico Carlo Besta

Milan, 20133, Italy

RECRUITING

Azienda Ospedaliera Univ.- Università Degli studi della Campania - Luigi Vanvitelli

Naples, 80138, Italy

RECRUITING

IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione

Pavia, 27100, Italy

RECRUITING

Azienda ospedaliera Sant'Andrea di Roma- Università di Roma La Sapienza

Roma, 00189, Italy

COMPLETED

Policlinico Universitario Agostino Gemelli

Roma, 168, Italy

RECRUITING

Chiba University Hospital

Chiba, 260 8677, Japan

COMPLETED

General Hanamaki Hospital

Hanamaki, 025-0082, Japan

RECRUITING

Hiroshima University Hospital

Hiroshima, 734 8551, Japan

RECRUITING

Teikyo University Hospital

Itabashi Ku, 173 8606, Japan

RECRUITING

St Marianna University Hospital

Kawasaki Shi, 216 8511, Japan

RECRUITING

Kagawa University Hospital

Kita Gun, 761 0793, Japan

COMPLETED

Kumamoto University Hospital

Kumamoto, 860-8556, Japan

COMPLETED

Iwate Medical University Hospital

Morioka, 020-8505, Japan

RECRUITING

National Hospital Organization Nagoya Medical Center

Nagoya, 460-0001, Japan

COMPLETED

Niigata City General Hospital

Niigata, 950-1197, Japan

RECRUITING

Hyogo College of Medicine Hospital

Nishinomiya-Shi, 663-8501, Japan

RECRUITING

Sapporo Medical University Hospital

Sapporo, 0608556, Japan

COMPLETED

Hokkaido Medical Center

Sapporo, 063 0005, Japan

RECRUITING

National Hospital Organization Sendai Medical Center

Sendai, 983-8520, Japan

RECRUITING

Tokushima University Hospital

Tokushima, 770-8503, Japan

COMPLETED

Tokyo Medical University Hospital

Tokyo, 160-0023, Japan

COMPLETED

iBiomed Research Unit

Aguascalientes, 20010, Mexico

COMPLETED

Consultorio Dr. Miguel Cortes

Cuernavaca, 62448, Mexico

RECRUITING

Hospital Civil de Guadalajara Fray Antonio Alcalde

Guadalajara, 44280, Mexico

RECRUITING

Neurocentrum Bydgoszcz Sp Z O O

Bydgoszcz, 85 796, Poland

RECRUITING

NZOZ Wielospecjalistyczna Poradnia Lekarska 'Synapsis'

Katowice, 40-123, Poland

RECRUITING

Centrum Neurologii Klinicznej Krakowska Akademia Neurologii

Krakow, 31 505, Poland

RECRUITING

Prywatny Gabinet Lekarski

Lublin, 20 093, Poland

RECRUITING

Centrum Medyczne NeuroProtect

Warsaw, 01-684, Poland

RECRUITING

Pusan National University Hospital

Busan, 49241, South Korea

RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, 41404, South Korea

RECRUITING

Kyungpook National University Hospital

Daegu, 41944, South Korea

COMPLETED

Severance Hospital Yonsei University Health System

Seoul, 120-752, South Korea

RECRUITING

Hosp. Gral. Univ. de Alicante

Alicante, 03010, Spain

RECRUITING

Hosp. de La Santa Creu I Sant Pau

Barcelona, 08025, Spain

RECRUITING

Hosp Univ Vall D Hebron

Barcelona, 08035, Spain

RECRUITING

Hosp Clinic de Barcelona

Barcelona, 8036, Spain

RECRUITING

Hosp. Univ. de Basurto

Bilbao, 48013, Spain

RECRUITING

Hosp. Virgen Macarena

Seville, 41009, Spain

RECRUITING

Hosp. Virgen Del Rocio

Seville, 41013, Spain

COMPLETED

Hosp. Univ. I Politecni La Fe

Valencia, 46026, Spain

RECRUITING

Karlstad Central Hospital

Karlstad, 651 85, Sweden

COMPLETED

Karolinska Universitetssjukhuset Solna

Stockholm, 171 76, Sweden

RECRUITING

China Medical University Hospital

Taichung, 40447, Taiwan

COMPLETED

Shin Kong Wu Ho Su Memorial Hospital

Taipei, 111, Taiwan

RECRUITING

Taipei Veterans General Hospital

Taipei, 11217, Taiwan

RECRUITING

Related Publications (3)

• Antozzi C, Fitzgibbon M. An evaluation of nipocalimab for the treatment of generalized myasthenia gravis. Expert Opin Biol Ther. 2025 Oct;25(10):1047-1058. doi: 10.1080/14712598.2025.2561935. Epub 2025 Sep 30.

  PMID: 41021216 DERIVED

• Raborn A, Savord A, Houts CR, Pease S, Scippa K, Ramchandren S. Psychometric analysis of the Neuro-QoL Fatigue in generalized Myasthenia Gravis (gMG) using data from a phase 3 trial. Qual Life Res. 2025 Sep;34(9):2577-2589. doi: 10.1007/s11136-025-03998-9. Epub 2025 Jun 14.

  PMID: 40515798 DERIVED

• Antozzi C, Vu T, Ramchandren S, Nowak RJ, Farmakidis C, Bril V, De Bleecker J, Yang H, Minks E, Park JS, Grudniak M, Smilowski M, Sevilla T, Hoffmann S, Sivakumar K, Suzuki Y, Youssef E, Sanga P, Karcher K, Zhu Y, Sheehan JJ, Sun H; Vivacity-MG3 Study Group. Safety and efficacy of nipocalimab in adults with generalised myasthenia gravis (Vivacity-MG3): a phase 3, randomised, double-blind, placebo-controlled study. Lancet Neurol. 2025 Feb;24(2):105-116. doi: 10.1016/S1474-4422(24)00498-8.

  PMID: 39862879 DERIVED

MeSH Terms

Conditions

Myasthenia Gravis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Neurodegenerative Diseases; Neuromuscular Junction Diseases; Neuromuscular Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Study Director
• Organization: Janssen Research & Development, LLC

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Janssen Research & Development, LLC Clinical Trial

  Janssen Research & Development, LLC

  STUDY DIRECTOR

Central Study Contacts

Study Contact

CONTACT

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

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR
• Expanded Access: Yes

Study Record Dates

• First Submitted: June 30, 2021
• First Posted: July 7, 2021
• Study Start: July 15, 2021
• Primary Completion: November 17, 2023
• Study Completion (Estimated): March 30, 2029
• Last Updated: March 3, 2026
• Results First Posted: July 23, 2025

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

ES (8); AU (2); PL (5); SE (2); FR (5); KR (4); IT (7); BE (5); US (24); CN (14); DK (2); CA (3); CZ (3); DE (6); TW (3); JP (16); ME (3)