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

NCT ID: NCT06463587

Last Updated: 2025-12-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE3

Total Enrollment

264 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-06-25

Study Completion Date

2030-08-19

Brief Summary

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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.

Detailed Description

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Conditions

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Generalized Myasthenia Gravis

Keywords

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Anti-AChR antibody positive anti-MuSK antibody positive anti-LRP4 antibody positive seronegative gMG

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Placebo

DBPC Period: Participants will be administered with Placebo, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.

BE Period: Participants initially randomized to placebo matched to cladribine in DBPC period will receive cladribine Low Dose or High Dose, orally as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated if clinically justified with placebo matched to cladribine.

RT Period: Participants requiring retreatment with cladribine Low Dose or High Dose or retreated with cladribine supplemental dose if clinically justified.

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

Participants will receive placebo matched to cladribine in two courses separated by 4 weeks.

Cladribine Low Dose

Intervention Type DRUG

Participants will receive cladribine low dose in two courses separated by 4 weeks.

Cladribine High Dose

Intervention Type DRUG

Participants will receive cladribine high dose in two courses separated by 4 weeks.

Cladribine Low Dose

DBPC Period: Participants will be administered with cladribine Low Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.

BE Period: Participants initially randomized to cladribine Low Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified.

RT Period: Participants requiring retreatment with cladribine Low Dose regimen and/or supplemental dose will receive the selected dose of cladribine if clinically justified.

Group Type EXPERIMENTAL

Cladribine Low Dose

Intervention Type DRUG

Participants will receive cladribine low dose in two courses separated by 4 weeks.

Cladribine High Dose

DBPC Period: Participants will be administered cladribine High Dose, orally as 2 separate treatment courses starting on Day 1 and at the beginning of Week 5.

BE Period: Participants initially randomized to cladribine High Dose in DBPC period will receive placebo matched to cladribine as 2 separate treatment courses starting at the beginning of Week 25 and at the beginning of Week 29 and retreated with cladribine supplemental dose if clinically justified.

RT Period: Participants requiring retreatment with cladribine High Dose regimen and/or supplemental dose will receive the selected dose of cladribine if clinically justified.

Group Type EXPERIMENTAL

Cladribine High Dose

Intervention Type DRUG

Participants will receive cladribine high dose in two courses separated by 4 weeks.

Interventions

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Placebo

Participants will receive placebo matched to cladribine in two courses separated by 4 weeks.

Intervention Type OTHER

Cladribine Low Dose

Participants will receive cladribine low dose in two courses separated by 4 weeks.

Intervention Type DRUG

Cladribine High Dose

Participants will receive cladribine high dose in two courses separated by 4 weeks.

Intervention Type DRUG

Eligibility Criteria

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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 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 or 16 mg/day for methylprednisolone
* If treated with acetylcholinesterase inhibitor should be on a stable daily dose (pyridostigmine dose ≤ 480 mg/day) for at least 3 months prior to and during screening
* Have a body weight \>= 40 kilograms

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 findings consistent with signs of infection such as PML, 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)
* Active malignancy, or history of cancer
* Treatment with nonsteroidal immunosuppressants, used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus within 4 weeks prior to randomization
* Treatment with eculizumab, rozanolixizumab efgartigimod, ravulizumab, or zilucoplan within 8 weeks prior to randomization
* History of thymectomy within 6 months prior to Screening.
* History of generalized seizures (except for history of infantile febrile seizures)
* Negative 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) within the last 2 years
* Discontinuation of treatment with any non-steroidal immunosuppressants used in gMG, such as azathioprine, mycophenolate mofetil, methotrexate, cyclosporine, tacrolimus within the last 6 months prior to Screening
* If treated with non-steroidal immunosuppressants for gMG, the dose at Screening should not exceed 50 mg/day for azathioprine, 500 mg/day for mycophenolate mofetil, 1 mg/day for tacrolimus, 50 mg/day for cyclosporine, 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role collaborator

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

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

EMD Serono Research & Development Institute, Inc.

Locations

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Arizona Neuroscience Research, LLC

Phoenix, Arizona, United States

Site Status RECRUITING

The George Washington University Medical Faculty Associates Foggy Bottom South Pavilion

Washington D.C., District of Columbia, United States

Site Status RECRUITING

Neurology of Central Florida Research Center, LLC

Altamonte Springs, Florida, United States

Site Status RECRUITING

SFM Clinical Research, LLC

Boca Raton, Florida, United States

Site Status RECRUITING

University of Florida Health Science Center - 300120311

Jacksonville, Florida, United States

Site Status RECRUITING

Neurology Associates, P. A.

Maitland, Florida, United States

Site Status RECRUITING

University of South Florida - PARENT - PARENT

Tampa, Florida, United States

Site Status RECRUITING

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, United States

Site Status RECRUITING

Clinical Trials of South Carolina - Charleston

Charleston, South Carolina, United States

Site Status RECRUITING

Erlanger Health, Inc. - 1123255

Chattanooga, Tennessee, United States

Site Status RECRUITING

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

Dallas, Texas, United States

Site Status RECRUITING

ANESC Research

El Paso, Texas, United States

Site Status RECRUITING

The University of Vermont Medical Center

Burlington, Vermont, United States

Site Status RECRUITING

Integrated Neurology Services - Dr. Simon Fishman's Office

Falls Church, Virginia, United States

Site Status RECRUITING

Expertia S.A- Mautalen Salud e Investigación

Ciudad Autonoma Buenos Aires, , Argentina

Site Status RECRUITING

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

Ciudad Autonoma Buenos Aires, , Argentina

Site Status RECRUITING

Instituto de Investigaciones Metabolicas (IDIM)

Ciudad Autonoma Buenos Aires, , Argentina

Site Status RECRUITING

Hospital Cordoba

Córdoba, , Argentina

Site Status RECRUITING

Fundacion Rosarina de Neurorehabilitacion

Rosario, , Argentina

Site Status RECRUITING

INECO Neurociencias Oroño

Rosario, , Argentina

Site Status RECRUITING

CER San Juan Centro Polivalente de Asistencia e Inv. Clinica

San Juan, , Argentina

Site Status RECRUITING

Centro de Investigaciones Medicas Tucuman

San Miguel de Tucumán, , Argentina

Site Status RECRUITING

Sunshine Coast University Hospital

Birtinya, Queensland, Australia

Site Status RECRUITING

Box Hill Hospital - PARENT

Box Hill, Victoria, Australia

Site Status RECRUITING

Gold Coast University Hospital - PARENT

Southport, , Australia

Site Status RECRUITING

Medical Center Hera - branch Montana

Montana, , Bulgaria

Site Status RECRUITING

The First Affiliated Hospital of Bengbu Medical College

Anhui Sheng, Anhui, China

Site Status RECRUITING

Xuanwu Hospital Capital Medical University

Beijing, Beijing Municipality, China

Site Status RECRUITING

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

Guangzhou, Guangdong, China

Site Status RECRUITING

Affiliated Hospital of Zunyi Medical University

Zunyi, Guizhou, China

Site Status RECRUITING

Shijiazhuang People's Hospital

Shijiazhuang, Hebei, China

Site Status RECRUITING

Henan Provincial People's Hospital

Zhengzhou, Henan, China

Site Status RECRUITING

Xiangya Hospital, Central South University

Changsha, Hu'nan, China

Site Status RECRUITING

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

Wuhan, Hubei, China

Site Status RECRUITING

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

Changchun, Jilin, China

Site Status RECRUITING

China-Japan Union Hospital of Jilin University - 300173736

Changchun, Jilin, China

Site Status RECRUITING

Huashan Hospital, Fudan University - Neurology

Shanghai, Shanghai Municipality, China

Site Status RECRUITING

Xi 'an International Medical Center

Xi’an, Shanxi, China

Site Status RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, China

Site Status RECRUITING

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

La Tronche, Isere, France

Site Status RECRUITING

Hopital Neurologique Pierre Wertheimer - Pathologies neuro-musculaires. Electromyographie

Bron, Rhone, France

Site Status RECRUITING

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

Paris, , France

Site Status RECRUITING

Ltd. Pineo Medical Ecosystem

Tbilisi, , Georgia

Site Status RECRUITING

New Hospitals LLC

Tbilisi, , Georgia

Site Status RECRUITING

Aversi Clinic Ltd

Tbilisi, , Georgia

Site Status RECRUITING

Bangalore Medical College and Victoria Hospital - 300148268

Bangalore, Karnataka, India

Site Status RECRUITING

Mallikatta Neurocentre

Mangalore, Karnataka, India

Site Status RECRUITING

IUHW Narita Hospital - Dept of Neurology

Narita-shi, Chiba, Japan

Site Status RECRUITING

Hakodate Municipal Hospital - Dept of Neurology

Hakodate-shi, Hokkaido, Japan

Site Status RECRUITING

General Hanamaki Hospital - Dept of Neurology

Hanamaki-shi, Iwate, Japan

Site Status RECRUITING

Kagawa University Hospital - Dept of Neurology

Kita-gun, Kagawa-ken, Japan

Site Status RECRUITING

Toho University Ohashi Medical Center - Dept of Neurology

Meguro-ku, Tokyo-To, Japan

Site Status RECRUITING

Tokyo Medical University Hospital - Dept of Neurology

Shinjuku-ku, Tokyo-To, Japan

Site Status RECRUITING

Osaka University Hospital - Dept of Neurology/Stroke Care Unit

Suita-shi, , Japan

Site Status RECRUITING

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

Krakow, , Poland

Site Status RECRUITING

Wielospecjalistyczne Centrum Medyczne Ibismed - Dept of Neurology

Zabrze, , Poland

Site Status RECRUITING

S.C Neurocity S.R.L

Bucharest, , Romania

Site Status RECRUITING

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

Târgu Mureş, , Romania

Site Status RECRUITING

Kyungpook National University Chilgok Hospital

Daegu, , South Korea

Site Status RECRUITING

Chonnam National University Hospital

Gwangju, , South Korea

Site Status RECRUITING

Samsung Medical Center

Seoul, , South Korea

Site Status RECRUITING

Korea University Anam Hospital

Seoul, , South Korea

Site Status RECRUITING

Asan Medical Center

Seoul, , South Korea

Site Status RECRUITING

Seoul Metropolitan Government Seoul National University Boramae Medical Center

Seoul, , South Korea

Site Status RECRUITING

Keimyung University Dongsan Hospital

Seoul, , South Korea

Site Status WITHDRAWN

Hospital Universitari Vall d'Hebron - Neurology Dept

Barcelona, , Spain

Site Status RECRUITING

Kaohsiung Chang Gung Memorial Hospital

Kaohsiung City, , Taiwan

Site Status RECRUITING

China Medical University Hospital

Taichung, , Taiwan

Site Status RECRUITING

Shin Kong Wu Ho-Su Memorial Hospital

Taipei, , Taiwan

Site Status RECRUITING

Taipei Veterans General Hospital

Taipei, , Taiwan

Site Status RECRUITING

Royal Hallamshire Hospital - Dept of Neurology

Sheffield, South Yorkshire, United Kingdom

Site Status RECRUITING

Countries

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Germany United States Argentina Australia Bulgaria China France Georgia India Japan Poland Romania South Korea Spain Taiwan United Kingdom

Central Contacts

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US Medical Information

Role: CONTACT

Phone: 888-275-7376

Email: [email protected]

Communication Center

Role: CONTACT

Phone: +49 6151 72 5200

Email: [email protected]

Facility Contacts

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Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2023-507746-83-00

Identifier Type: OTHER

Identifier Source: secondary_id

MS700568_0183

Identifier Type: -

Identifier Source: org_study_id