A Study of Nipocalimab Administered to Adults With Generalized Myasthenia Gravis

Официальное название

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

Обзор

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.

Вмешательства

• Препарат Nipocalimab
  Nipocalimab will be administered as an IV infusion.
• Препарат Placebo
  Matching placebo will be administered as an IV infusion.
• Препарат Nipocalimab SC-LIV
  Nipocalimab will be administered subcutaneously.

Первичные конечные точки

• 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 [Срок оценки: 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) [Срок оценки: 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) [Срок оценки: From pre-first nipocalimab dose on Day 1 up to Week 8 (Day 57)]

Вторичные конечные точки (12)

• DB Phase: Average Change From Baseline in Quantitative Myasthenia Gravis (QMG) Score Over Weeks 22 and 24 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Weeks 22, 23, and 24]
• Percentage of Participants With Treatment-emergent Adverse Events (TEAEs) [Срок оценки: From start of treatment (DB phase Day 1) up to 4 years 9 months]
• Percentage of Participants With Treatment-emergent Serious Adverse Events (TESAEs) [Срок оценки: From start of treatment (DB phase Day 1) up to 4 years 9 months]
• Percentage of Participants With AEs of Special Interest (AESIs) [Срок оценки: From start of treatment (DB phase Day 1) up to 4 years 9 months]
• Number of Participants With Change in Vital Signs [Срок оценки: From start of treatment (DB phase Day 1) up to 4 years 9 months]
• Number of Participants With Change in Clinical Laboratory Values [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: Baseline, Week 2 up to Week 24]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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)

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 24 центра

• Neuromuscular Research Center and Clinic — Paradise Valley
• HonorHealth Neurology — Scottsdale
• University of Southern California — Los Angeles
• Stanford University — Palo Alto
• Care Access Research — Pasadena
• University of Colorado Anschutz Medical Campus — Aurora
• Yale New Haven Hospital — New Haven
• FM Clinical Research, LLC South Florida Neurology Associates, P. A. — Boca Raton
• … и ещё 16 центров

Япония · 16 центров

• Chiba University Hospital — Chiba
• General Hanamaki Hospital — Hanamaki
• Hiroshima University Hospital — Hiroshima
• Teikyo University Hospital — Itabashi Ku
• St Marianna University Hospital — Kawasaki Shi
• Kagawa University Hospital — Kita Gun
• Kumamoto University Hospital — Kumamoto
• National Hospital Organization Nagoya Medical Center — Nagoya
• … и ещё 8 центров

Китай · 14 центров

• Beijing Tiantan Hospital, Capital Medical University — Пекин
• Xuanwu Hospital ,Capital Medical University — Пекин
• Beijing Hospital — Пекин
• The First Bethune Hospital of Jilin University — Changchun
• Xiangya Hospital Central South University — Чанша
• West China Hospital of Sichuan University — Чэнду
• Fujian Medical University Union Hospital — Фучжоу
• The First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine — Гуанчжоу
• … и ещё 6 центров

Испания · 8 центров

Список центров уточняется — проверьте первичный протокол.

Италия · 7 центров

• U.O.P.I. di Psichiatria — Catania
• Fondazione Istituto G. Giglio — Cefalù
• Istituto Neurologico Carlo Besta — Milan
• Azienda Ospedaliera Univ.- Università Degli studi della Campania - Luigi Vanvitelli — Naples
• IRCCS C. Mondino, Istituto Neurologico Nazionale, Fondazione — Pavia
• Azienda ospedaliera Sant'Andrea di Roma- Università di Roma La Sapienza — Roma
• Policlinico Universitario Agostino Gemelli — Roma

Германия · 6 центров

• NeuroCure Clinical Research Center — Berlin
• Universitatsmedizin Gottingen — Göttingen
• Universitaetsklinikum Leipzig — Leipzig
• Universitatsklinikum Schleswig Holstein Campus Lubeck — Lübeck
• Universitatsklinikum Ulm — Ulm
• DKD HELIOS Klinik Wiesbaden, Fachbereich Neurologie — Wiesbaden

Бельгия · 5 центров

• ULB Hôpital Erasme — Anderlecht
• AZ Sint Jan Brugge Oostende AV — Bruges
• Cliniques Universitaires Saint Luc — Brussels
• AZ Sint-Lucas — Ghent
• University Hospitals Leuven — Leuven

Франция · 5 центров

• Hopital Pierre Wertheimer — Bron
• CHU Grenoble — Grenoble
• Hopital de la Pitie Salpetriere — Paris
• Hopital Pasteur 1 — Provence-Alpes-Côte d'Azur
• Hopital PASTEUR — Provence-Alpes-Côte d'Azur

Польша · 5 центров

Список центров уточняется — проверьте первичный протокол.

South Korea · 4 центра

Список центров уточняется — проверьте первичный протокол.

Канада · 3 центра

• The Ottawa Hospital Research Institute — Ottawa
• Toronto General Hospital — Toronto
• McGill University — Montreal

Чехия · 3 центра

• Neurologie a rehabilitace Skopalíkova — Brno
• Fakultni nemocnice Brno — Brno
• Vseobecna Fakultní Nemocnice — Prague

Мексика · 3 центра

Список центров уточняется — проверьте первичный протокол.

Тайвань · 3 центра

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Австралия · 2 центра

• Melbourne Neurology Group — North Melbourne
• Gold Coast University Hospital — Southport

Дания · 2 центра

• Aalborg University Hospital — Aalborg
• Rigshospitalet — København Ø

Швеция · 2 центра

Список центров уточняется — проверьте первичный протокол.

Публикации

• Yu F, Myshkin E, Nguyen B, Bobadilla Mendez C, Cossu M, Fei K, Wang Q, Hubbard JJ, Campbell K, Ramchandren S, Rojo Cella R, Edwards R, Taylor PC, Gottenberg JE, Noaiseh G, Vu T, Antozzi C, Winthrop KL, Cuff CA, Loza MJ, Dimitrova D, Gao S. Effect of nipocalimab on IgG responses to vaccinations and viral infections in patients with IgG autoantibody-mediated diseases: Post hoc analyses of three rand PMID 42084498
• 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
• 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
• 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- PMID 39862879

Идентификаторы

NCT: NCT04951622 · CR109046 · MOM-M281-011 · 2020-005732-29 · 2023-504152-97-00

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗