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

RecruitingPhase 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)

Who can join

Ages 18 and older · All sexes

Full eligibility criteria
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

About the study

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.

What is being tested

Sponsor: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany · Participants: 264 · Started: Jun 25, 2024

Contact the study team

Official record on ClinicalTrials.gov — NCT06463587

Locations in the U.S.

ArizonaArizona Neuroscience Research, LLC, Phoenix
ConnecticutUniversity of Connecticut Health Center - Department of Medicine, Farmington
District of ColumbiaThe George Washington University Medical Faculty Associates Foggy Bottom South Pavilion, Washington D.C.
FloridaNeurology of Central Florida Research Center, LLC, Altamonte Springs
SFM Clinical Research, LLC, Boca Raton
University of Florida Health Science Center - 300120311, Jacksonville
Neurology Associates, P. A., Maitland
University of South Florida - PARENT - PARENT, Tampa
KansasUniversity of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN), Kansas City
North CarolinaUNC Hospitals - PARENT, Chapel Hill
Atrium Health Wake Forest Baptist, Winston-Salem
OhioMiami Valley Hospital South, Centerville
University of Cincinnati, Cincinnati
South CarolinaClinical Trials of South Carolina - Charleston, Charleston
TennesseeErlanger Health, Inc. - 1123255, Chattanooga
TexasBaylor Scott & White Research Institute - Baylor Scott & White Research Institute, Dallas
ANESC Research, El Paso
Baylor Scott & White Neurology - McKinney, McKinney
VermontThe University of Vermont Medical Center, Burlington

Conditions

From ClinicalTrials.gov, data retrieved Sep 30, 2026. Each study sets its own eligibility; the study team decides who can join.