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RecruitingInterventionalPhase 3

A Phase 3, Randomized, Double-Blind, Placebo-Controlled, 3-Arm, 3-Period Study to Assess the Efficacy and Safety of a New Formulation of Oral Cladribine Compared With Placebo in Participants With Generalized Myasthenia Gravis (MyClad)

NCT ID: NCT06463587Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, GermanyLast updated: 2026-05-22

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.

Arms & interventions

  • OtherPlacebo

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

  • DrugCladribine Low Dose

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

  • DrugCladribine High Dose

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

Outcome measures

Primary

  • Change from Baseline in Myasthenia Gravis - Activities of Daily Living (MG-ADL) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: Baseline, Week 24

Secondary

  • Change from Baseline in Quantitative Myasthenia Gravis (QMG) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: Baseline, Week 24

  • Percentage of MG-ADL Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: At Week 24

  • Change from Baseline in Myasthenia Gravis Composite (MGC) Scale Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: Baseline, Week 24

  • Percentage of Quantitative Myasthenia Gravis (QMG) Scale Responders at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: At Week 24

  • Time From Initial Cladribine Full Dose Treatment to First Retreatment or Rescue Treatment up to end of Study

    Time frame: Up to End of Study (Week 144)

  • Number of Participants With Adverse Events (AEs) and Adverse Events of Special Interest (AESIs)

    Time frame: Up to End of Study (Week 144)

  • Number of participants with Adverse Events (AEs) by Severity as per National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0

    Time frame: Up to End of Study (Week 144)

  • Number of Participants with Abnormal Laboratory Variables including Absolute Lymphocyte Count and Vital Signs

    Time frame: Up to End of Study (Week 144)

  • Pharmacokinetic (PK) Plasma Concentration of Cladribine

    Time frame: Pre-dose, 0.25, 1, 2, 3, 4, 6, 8 and 24 hours post-dose

  • Change from Baseline in the Revised Myasthenia Gravis Quality of Life - 15 Scale (MG-Qol15r) Score at Week 24 During the Double-Blind Placebo Controlled (DBPC) Period

    Time frame: Baseline, Week 24

  • Number of Participants with Abnormal ECG parameters

    Time frame: Up to End of Study (Week 144)

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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

Study locations (21)

Arizona Neuroscience Research, LLC

Phoenix, Arizona, 85032

Recruiting
Leslie Zuniga · Principal Investigator

Advanced Neurosciences Research LLC

Longmont, Colorado, 80501

Recruiting
Ning Sarah Yang · Principal Investigator

University of Connecticut Health Center - Department of Medicine

Farmington, Connecticut, 06030-5550

Recruiting
Amanda Hernandez · Principal Investigator

The George Washington University Medical Faculty Associates Foggy Bottom South Pavilion

Washington D.C., District of Columbia, 20037

Recruiting
Henry J Kaminski · Principal Investigator

Neurology of Central Florida Research Center, LLC

Altamonte Springs, Florida, 32714

Recruiting
Alicia V Cabrera · Principal Investigator

SFM Clinical Research, LLC

Boca Raton, Florida, 33487

Recruiting
Marc H Feinberg · Principal Investigator

University of Florida Health Science Center - 300120311

Jacksonville, Florida, 32209

Recruiting
Michael T Pulley · Principal Investigator

Neurology Associates, P. A.

Maitland, Florida, 32751

Recruiting
Adam D Slansky · Principal Investigator

University of South Florida - PARENT - PARENT

Tampa, Florida, 33612

Recruiting
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Tuan H Vu · Principal Investigator

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

Kansas City, Kansas, 66160

Recruiting
Mamatha Pasnoor · Principal Investigator

UNC Hospitals - PARENT

Chapel Hill, North Carolina, 27599

Recruiting
James F Howard · Principal Investigator

Atrium Health Wake Forest Baptist

Winston-Salem, North Carolina, 27157-1078

Recruiting
Rachana B Gandhi Mehta · Principal Investigator

Miami Valley Hospital South

Centerville, Ohio, 45459

Recruiting
Jon P Williams · Principal Investigator

University of Cincinnati

Cincinnati, Ohio, 45219

Recruiting
Hani Kushlaf · Principal Investigator

Clinical Trials of South Carolina - Charleston

Charleston, South Carolina, 29406

Recruiting
David E Stickler · Principal Investigator

Erlanger Health, Inc. - 1123255

Chattanooga, Tennessee, 37403

Recruiting
Chelsea A Shugars · Principal Investigator

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

Dallas, Texas, 75246

Recruiting
Niloofar Yari · Principal Investigator

ANESC Research

El Paso, Texas, 79912

Recruiting
Aamr A Herekar · Principal Investigator

Baylor Scott & White Neurology - McKinney

McKinney, Texas, 75071

Recruiting
Francy Shu · Principal Investigator

The University of Vermont Medical Center

Burlington, Vermont, 05401

Recruiting
Rup Tandan · Principal Investigator

Integrated Neurology Services - Dr. Simon Fishman's Office

Falls Church, Virginia, 22043

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