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NCT06463587PHASE3Recruiting

Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis (MyClad)

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Start Date

6/25/2024

Completion Date

11/12/2030

Summary

The purpose of this clinical study is to determine the efficacy and safety of a new oral cladribine formulation in participants with Generalized Myasthenia Gravis (gMG) in comparison to placebo. It will also investigate the sustained efficacy, the need for retreatment, and the long-term safety of oral cladribine in gMG. An additional component is included to characterize the Pharmacokinetics (PK) of the new cladribine formulation in gMG participants. This study is divided into 3 periods: the double-blind placebo control (DBPC) pivotal period, and 2 extensions, the blinded extension (BE) and the retreatment (RT) period. Furthermore, in trial interviews will be conducted as a sub-study to MyClad with a sub-set of participants to gain an in depth understanding of the participant cladribine treatment and study experience.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Adults of ≥ 18 years of age at the time of signing the informed consent. * Diagnosis of Myasthenia Gravis with generalized muscle weakness, meeting clinical criteria for Myasthenia Gravis Foundation of America Class II to IVa classification. * In participants positive for Acetylcholine receptor antibody (anti-AChR) or muscle-specific kinase antibody(anti-MuSK) * In participants that are autoantibody seronegative i.e. not positive for anti-AChR and anti-MuSK antibodies and participants who are positive for anti-low-density lipoprotein receptor-related protein 4 antibodies (anti-LRP4) * Has a Screening and Baseline MG-ADL score more than or equal to (\>=) 6 with \>= 50 percentage (%) of the total score due to non-ocular symptoms. Screening and Baseline MG-ADL scores must be stable. The difference between the Screening and Baseline scores should not be more than 2 and there should be no reported MG exacerbation during the Screening period * If treated with oral corticosteroids: should be on a stable daily dose for at least 3 months prior to and during screening. In such case, the daily dose of oral steroids should not exceed 20 milligrams(mg)/day for prednisone/ prednisolone, 16 mg/day for methylprednisolone, 3 mg/day for dexamethasone, or 80 mg for hydrocortisone or equivalent doses for other corticosteroids. * If treated with acetylcholinesterase inhibitor should be on a stable daily dose (pyridostigmine dose ≤ 480 mg/day or neostigmine ≤ 300 mg/day) for at least 3 months prior to and during screening * Have a body weight \>= 40 kilograms * Other protocol defined inclusion criteria could apply Exclusion Criteria: * Immunologic disorder other than MG or any other condition requiring chronic oral, intravenous, intramuscular, or intraarticular corticosteroid therapy. Well-controlled thyroid disease, as per the Treating Investigator or the participants regular treating physician recorded in the source documents, is not exclusionary * Molecularly characterized or suspected congenital myasthenic syndrome, Lambert-Eaton myasthenic syndrome, inherited myopathy, muscular dystrophy, acquired myopathy or any other neurologic or systematic disease that mimics MG muscular weakness * Active, clinically significant viral, bacterial, or fungal infection, including brain MRI or chest X-ray findings consistent with signs of infection such as PML or TB, or any major episode of infection requiring hospitalization or treatment with parenteral anti-infectives within 8 weeks prior or during Screening, or completion of oral anti-infectives within 8 weeks prior or during Screening. Vaginal candidiasis, onychomycosis, and genital or oral herpes simplex virus considered by the Investigator to be sufficiently controlled would not be exclusionary * Has a history of or current diagnosis of active tuberculosis (TB) or is currently undergoing treatment for latent TB infection or has an untreated latent TB infection as determined by documented results within 3 months of the Screening Visit of a positive TB skin test . * Active malignancy, or history of cancer or signs of malignancy in any Screening assessment * Treatment with nonsteroidal immunosuppressants, used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, cyclophosphamide, tacrolimus within 4 weeks prior to randomization * Treatment with FcRn or complement inhibitors (such as eculizumab, rozanolixizumab efgartigimod, ravulizumab, zilucoplan or nipocalimab) within 8 weeks prior to randomization * History of thymectomy within 6 months prior to Screening. * History of generalized seizures (except for history of febrile seizures during the participant's childhood). * Negative or indeterminate for Varicella Zoster Virus antibodies at screening * History of myasthenic crisis in the last 12 months prior to and during screening * History of recurrent infections (that is 3 or more infections per year documented in available source data) within the last 2 years * Discontinuation of treatment with any non-steroidal immunosuppressants used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, cyclophosphamide, tacrolimus within the last 6 months prior to Screening * If treated with non-steroidal immunosuppressants for gMG, the dose at Screening higher than 50 mg/day for azathioprine, 500 mg/day for mycophenolate mofetil, 1 mg/day for tacrolimus, 50 mg/day for cyclosporine, 25 mg/day for cyclophosphamide, or 7.5 mg/week for methotrexate * Participation in clinical study of any investigational drug within 6 months, or 5 half-lives of the investigational drug used in the previous clinical study prior to randomization, whichever is longer. However, participants with any prior exposure to cladribine may not enter the study regardless of timing of exposure * Other protocol defined exclusion criteria could apply

Interventions

OTHER

Placebo

DRUG

Cladribine Low Dose

DRUG

Cladribine High Dose

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Conditions

Generalized Myasthenia Gravis

Locations

Arizona Neuroscience Research, LLC

Phoenix, Arizona 85032

United States

Advanced Neurosciences Research LLC

Longmont, Colorado 80501

United States

University of Connecticut Health Center - Department of Medicine

Farmington, Connecticut 06030-5550

United States

The George Washington University Medical Faculty Associates Foggy Bottom South Pavilion

Washington D.C., District of Columbia 20037

United States

Neurology of Central Florida Research Center, LLC

Altamonte Springs, Florida 32714

United States

SFM Clinical Research, LLC

Boca Raton, Florida 33487

United States

University of Florida Health Science Center - 300120311

Jacksonville, Florida 32209

United States

Neurology Associates, P. A.

Maitland, Florida 32751

United States

University of South Florida - PARENT - PARENT

Tampa, Florida 33612

United States

University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)

Kansas City, Kansas 66160

United States

UNC Hospitals - PARENT

Chapel Hill, North Carolina 27599

United States

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina 27157-1078

United States

Miami Valley Hospital South

Centerville, Ohio 45459

United States

University of Cincinnati

Cincinnati, Ohio 45219

United States

Clinical Trials of South Carolina - Charleston

Charleston, South Carolina 29406

United States

Erlanger Health, Inc. - 1123255

Chattanooga, Tennessee 37403

United States

Baylor Scott & White Research Institute - Baylor Scott & White Research Institute

Dallas, Texas 75246

United States

ANESC Research

El Paso, Texas 79912

United States

Baylor Scott & White Neurology - McKinney

McKinney, Texas 75071

United States

The University of Vermont Medical Center

Burlington, Vermont 05401

United States

Integrated Neurology Services - Dr. Simon Fishman's Office

Falls Church, Virginia 22043

United States

Expertia S.A- Mautalen Salud e Investigación

Ciudad Autonoma Buenos Aires, 1427

Argentina

Instituto de Investigaciones Neurologicas Raul Carrea, FLENI - de Investigaciones Clinicas del área de Cardiología y enfermedades metabólicas asociadas

Ciudad Autonoma Buenos Aires, 1428

Argentina

Instituto de Investigaciones Metabolicas (IDIM)

Ciudad Autonoma Buenos Aires, C1012AAR

Argentina

Hospital Cordoba

Córdoba,

Argentina

Fundacion Rosarina de Neurorehabilitacion

Rosario,

Argentina

INECO Neurociencias Oroño

Rosario,

Argentina

CER San Juan Centro Polivalente de Asistencia e Inv. Clinica

San Juan, 5400

Argentina

Centro de Investigaciones Medicas Tucuman

San Miguel de Tucumán,

Argentina

Brain and Mind Research Institute

Camperdown, New South Wales 2050

Australia

Sunshine Coast University Hospital

Birtinya, Queensland 4575

Australia

Princess Alexandra Hospital - PARENT

South Brisbane, Queensland 4101

Australia

John Hunter Hospital - PARENT

City of Burnside, South Australia SA 5072

Australia

Box Hill Hospital - PARENT

Box Hill, Victoria 3128

Australia

Gold Coast University Hospital - PARENT

Southport,

Australia

UZ Leuven

Leuven, 3000

Belgium

C. H. R. de la Citadelle - Account 1

Liège, 4000

Belgium

Medical Center Hera - branch Montana

Montana, 3400

Bulgaria

UMHAT 'Dr. Georgi Stranski', EAD

Pleven, 5800

Bulgaria

UMHAT "Sv. Georgi", EAD

Plovdiv, 4000

Bulgaria

MHATNP "Sv.Naum", EAD - Third Neurology Clinic

Sofia, 1113

Bulgaria

UMHATEM 'N.I. Pirogov', EAD

Sofia, 1606

Bulgaria

Burnaby Hospital - Fraser Health Multiple Sclerosis Clinic

Burnaby, British Columbia V5G 2X6

Canada

The First Affiliated Hospital of Bengbu Medical College

Anhui Sheng, Anhui 233000

China

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality 100053

China

Peking Union Medical College Hospital

Beijing, Beijing Municipality 100730

China

The First Affiliated Hospital of Guangzhou University of Chinese Medicine - 300164595

Guangzhou, Guangdong 510405

China

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou 563099

China

Shijiazhuang People's Hospital

Shijiazhuang, Hebei 050000

China

Henan Provincial People's Hospital

Zhengzhou, Henan 450003

China

Xiangya Hospital, Central South University

Changsha, Hu'nan 410008

China

Tongji Hospital, Tongji Medical College, Huazhong University of Science & Technology

Wuhan, Hubei 430030

China

The First Hospital of Jilin University - The First Hospital of Jilin University

Changchun, Jilin 130021

China

China-Japan Union Hospital of Jilin University - 300173736

Changchun, Jilin 130033

China

Shengjing Hospital of China Medical University

Shenyang, Liaoning 110004

China

Huashan Hospital, Fudan University - Neurology

Shanghai, Shanghai Municipality 200040

China

Xi 'an International Medical Center

Xi’an, Shanxi 710038

China

West China Hospital, Sichuan University

Chengdu, Sichuan 610041

China

CHU Nice - Hôpital Pasteur - Cardiology

Nice, Alpes Maritimes 06002

France

CHU Strasbourg - Hopital Hautepierre - Service Anesthesie-Reanimation&Medecine Peri-Opera

Strasbourg, Bas Rhin 67098

France

CHU de Grenoble - Hôpital Albert Michallon - Centre de Références des Maladies Neuromusculaires

La Tronche, Isere 38700

France

Fondation Ophtalmologique Adolphe de Rothschild - Service de neurologie

Paris, Paris 75940

France

CHU Clermont Ferrand - Hopital Gabriel Montpied - service de neurologie B

Clermont-Ferrand, Puy De Dome 63003

France

Hopital Neurologique Pierre Wertheimer - Pathologies neuro-musculaires. Electromyographie

Bron, Rhone 69677

France

Hôpital Henri Mondor - Service de Neurologie

Créteil, Val De Marne 94010

France

Groupe Hospitalier Pitie-Salpetriere - Centre Référent Maladies Rares SLA - Neurologie

Paris, 75013

France

Ltd. Pineo Medical Ecosystem

Tbilisi, 0114

Georgia

New Hospitals LLC

Tbilisi, 0114

Georgia

Aversi Clinic Ltd

Tbilisi, 0160

Georgia

Universitaetsklinikum Ulm - Klinik fuer Neurologie

Ulm, Baden-Wurttemberg 89081

Germany

Universitaetsmedizin Goettingen - Abteilung fuer Nephrologie und Rheumatologie

Göttingen, Lower Saxony 37075

Germany

Medizinische Hochschule Hannover - Klinik fur Neurologie mit Klinischer Neurophysiol

Hanover, Lower Saxony 30625

Germany

St. Joseph Hospital - St. Joseph Hospital Haan

Bochum, North Rhine-Westphalia 44791

Germany

Universitaetsklinikum Duesseldorf AoeR - Klinik fuer Neurologie

Düsseldorf, North Rhine-Westphalia 40225

Germany

Universitaetsklinikum Carl Gustav Carus TU Dresden - Medizinische Klinik I

Dresden, Saxony 01307

Germany

Universitaetsklinikum Leipzig AoeR - Klinik und Poliklinik fuer Neurologie

Leipzig, Saxony 04103

Germany

Universitaetsklinikum Schleswig-Holstein - Campus Luebeck - Neurologie

Lübeck, Schleswig-Holstein 23562

Germany

Charité Universitaetsmedizin Berlin - Campus Charité Mitte - Klinik fuer Neurologie

Berlin, 10117

Germany

University General Hospital of Larissa - Rheumatology Clinic

Larissa, 41500

Greece

University Hospital of Patra

Pátrai, 26504

Greece

AHEPA General Hospital of Thessaloniki

Thessaloniki, 54636

Greece

Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kozpont - Neurologiai Klinika

Szeged, 6725

Hungary

Nizam's Institute of Medical Sciences

Hyderabad, Andhra Pradesh 500082

India

Yashoda Super Speciality Hospital - 300158817

Hyderabad, Andhra Pradesh 500082

India

Bangalore Medical College and Victoria Hospital - 300148268

Bangalore, Karnataka 560002

India

St John's Medical College Hospital

Bangalore, Karnataka 560034

India

Mallikatta Neurocentre

Mangalore, Karnataka 575001

India

Chopda Medicare & Research Centre - 300188248

Nashik, Maharashtra 422005

India

Deenanath Mangeshkar Hospital and Research Centre - Department of Neurology

Pune, Maharashtra 411030

India

Policlinico Universitario Agostino Gemelli - UOC Neurologia

Rome, Roma 00168

Italy

Azienda Socio Sanitaria Territoriale Papa Giovanni

Bergamo, 24127

Italy

IRCCS Istituto delle Scienze Neurologiche di Bologna - Unità Operativa Complessa Clinica Neurologica

Bologna, 40139

Italy

IRCCS Ospedale Policlinico San Martino - Neuroradiologia

Genova, 16132

Italy

Fondazione IRCCS Istituto Neurologico Carlo Besta

Milan, 20133

Italy

Fondazione Istituto Neurologico Casimiro Mondino - Neurology

Pavia, 27100

Italy

Azienda Ospedaliera Universitaria Policlinico Tor Vergata - U.O.C. Neurologia

Roma, 00133

Italy

Ospedale ca' Foncello - Neurology

Treviso, 31100

Italy

Chiba University Hospital - Dept of Neurology

Chiba, Chiba 260-8677

Japan

IUHW Narita Hospital - Dept of Neurology

Narita-shi, Chiba 286-8520

Japan

Fukuoka University Hospital - Dept of Neurology/Health Care

Fukuoka, Fukuoka 814-0180

Japan

Southern Tohoku Medical Clinic - Dept of Neurology

Koriyama-shi, Fukushima 963-8563

Japan

Hakodate Municipal Hospital - Dept of Neurology

Hakodate-shi, Hokkaido 392006

Japan

General Hanamaki Hospital - Dept of Neurology

Hanamaki-shi, Iwate 025-0082

Japan

Kagawa University Hospital - Dept of Neurology

Kita-gun, Kagawa-ken 7610793

Japan

Nagasaki University Hospital - Dept of Neurology

Nagasaki, Nagasaki 852-8501

Japan

Saitama Medical University Hospital - Dept of Neurology/Stroke Care Unit

Iruma-gun, Saitama 350-0495

Japan

Toho University Ohashi Medical Center - Dept of Neurology

Meguro-ku, Tokyo-To 153-8515

Japan

Tokyo Medical University Hospital - Dept of Neurology

Shinjuku-ku, Tokyo-To 160-0023

Japan

Osaka University Hospital - Dept of Neurology/Stroke Care Unit

Suita-shi,

Japan

Uniwersyteckie Centrum Kliniczne - Dept of Neurology

Gdansk, 80-214

Poland

SP ZOZ Szpital Uniwersytecki w Krakowie - Zespó

Krakow, 30-688

Poland

Krakowska Akademia Neurologii Sp z o.o. Centrum Neurologii Klinicznej

Krakow, 31-505

Poland

MTZ Clinical Research Powered By Pratia

Warsaw, 02-091

Poland

Wielospecjalistyczne Centrum Medyczne Ibismed - Dept of Neurology

Zabrze,

Poland

Institutul Clinic Fundeni - parent

Bucharest, 022328

Romania

S.C Neurocity S.R.L

Bucharest, 040215

Romania

Brainaxy Clinic S.R.L.

Constanța, 900591

Romania

Spitalul Clinic Judetean de Urgenta Targu Mures - Sectia Clinica Neurologie I

Târgu Mureş, 540136

Romania

Kyungpook National University Chilgok Hospital

Daegu, 41404

South Korea

Chonnam National University Hospital

Gwangju, 61469

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Korea University Anam Hospital

Seoul, 136-705

South Korea

Asan Medical Center

Seoul, 138-736

South Korea

Seoul Metropolitan Government Seoul National University Boramae Medical Center

Seoul, 156707

South Korea

Keimyung University Dongsan Hospital

Seoul,

South Korea

Hospital Universitari Germans Trias i Pujol - Servicio de Neurologia

Badalona, Barcelona 08916

Spain

Hospital Universitario Reina Sofia - Neurology Dept

Córdoba, Córdoba 14004

Spain

Hospital Universitario Central de Asturias - Servicio de Neurologia

Oviedo, Principality of Asturias 33011

Spain

Hospital Universitari Vall d'Hebron - Neurology Dept

Barcelona, 08035

Spain

Hospital Universitari i Politecnic La Fe - Pediatry Department

Valencia, 46026

Spain

Sahlgrenska Sjukhuset

Göteborg, 41345

Sweden

Centralsjukhuset Karlstad

Karlstad, 65230

Sweden

Danderyd Sjukhus - 300147691

Stockholm, 18288

Sweden

Inselspital - Universitaetsspital Bern - Neuropsychologische Rehabilitation, Neurologie

Bern, 3010

Switzerland

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, 83301

Taiwan

China Medical University Hospital

Taichung, 404327

Taiwan

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, 111

Taiwan

Taipei Veterans General Hospital

Taipei, 11217

Taiwan

Hacettepe University Medical Faculty - Neurology Department

Ankara, 06100

Turkey (Türkiye)

Ondokuz Mayis Univ. Med. Fac. - Neurology

Atakum/SAMSUN, 55270

Turkey (Türkiye)

Kocaeli University Medical Faculty - Neurology Department

Kocaeli, 41380

Turkey (Türkiye)

Mersin University Medical Faculty - Neurology Department

Mersin, 33079

Turkey (Türkiye)

Karadeniz Tecnical Uni. Med. Fac. - Neurology Departmen

Trabzon, 61080

Turkey (Türkiye)

Nottingham University Hospitals NHS Trust

Nottingham, Nottinghamshire NG7 2UH

United Kingdom

Royal Hallamshire Hospital - Dept of Neurology

Sheffield, South Yorkshire S10 2JF

United Kingdom