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RECRUITINGPhase 3INTERVENTIONAL

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

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)

Important: This information is not medical advice. Talk to your doctor about whether a clinical trial is right for you.

About This Trial

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.

Who May Be Eligible (Plain English)

Who May Qualify: - Adults of ≥ 18 years of age at the time of signing the willing to sign a consent form. - 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 - Other protocol defined inclusion criteria could apply Who Should NOT Join This Trial: - 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 ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language
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 * 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 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 * Other protocol defined exclusion criteria could apply

Treatments Being Tested

OTHER

Placebo

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

DRUG

Cladribine Low Dose

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

DRUG

Cladribine High Dose

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

Locations (20)

Arizona Neuroscience Research, LLC
Phoenix, Arizona, United States
Advanced Neurosciences Research LLC
Longmont, Colorado, United States
The George Washington University Medical Faculty Associates Foggy Bottom South Pavilion
Washington D.C., District of Columbia, United States
Neurology of Central Florida Research Center, LLC
Altamonte Springs, Florida, United States
SFM Clinical Research, LLC
Boca Raton, Florida, United States
University of Florida Health Science Center - 300120311
Jacksonville, Florida, United States
Neurology Associates, P. A.
Maitland, Florida, United States
University of South Florida - PARENT - PARENT
Tampa, Florida, United States
University of Kansas Medical Center Research Institute, Inc. - 3901 Rainbow (MAIN)
Kansas City, Kansas, United States
UNC Hospitals - PARENT
Chapel Hill, North Carolina, United States
Atrium Health Wake Forest Baptist
Winston-Salem, North Carolina, United States
Miami Valley Hospital South
Centerville, Ohio, United States
Clinical Trials of South Carolina - Charleston
Charleston, South Carolina, United States
Erlanger Health, Inc. - 1123255
Chattanooga, Tennessee, United States
Baylor Scott & White Research Institute - Baylor Scott & White Research Institute
Dallas, Texas, United States
ANESC Research
El Paso, Texas, United States
Baylor Scott & White Neurology - McKinney
McKinney, Texas, United States
The University of Vermont Medical Center
Burlington, Vermont, United States
Integrated Neurology Services - Dr. Simon Fishman's Office
Falls Church, Virginia, United States
Expertia S.A- Mautalen Salud e Investigación
Ciudad Autonoma Buenos Aires, Argentina