Recruiting
Phase 3

Cladribine

Sponsor:

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

Code:

NCT06463587

Conditions

Generalized Myasthenia Gravis

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Placebo

Cladribine Low Dose

Cladribine High Dose

Study Details

Brief 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.

Conditions

Generalized Myasthenia Gravis

Study ID

NCT06463587

Start date

Jun 25, 2024

Status verified date

Aug, 2026

Completion date

Nov 12, 2030

Anticipated

Primary completion date

Aug 23, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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 Design

Enrollment

264 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

placebo comparator: 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: If clinically justified, participants requiring retreatment with cladribine Low Dose or High Dose or cladribine supplemental dose will receive the selected dose of cladribine or matching placebo regimen.

experimental: 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: If clinically justified, participants requiring retreatment with cladribine Low Dose regimen and/or supplemental dose will receive the selected dose of cladribine or matching placebo regimen.

experimental: 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: If clinically justified, participants requiring retreatment with cladribine High Dose regimen and/or supplemental dose will receive the selected dose of cladribine or matching placebo regimen.

Interventions

Placebo

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

Cladribine Low Dose

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

Cladribine High Dose

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

Primary outcome measure

  • 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 ]

Central Contacts and Locations

Central contacts

US Medical Information

888-275-7376eMediUSA@emdserono.com

Communication Center

+49 6151 72 5200service@emdgroup.com

Locations

Arizona Neuroscience Research, LLC

Recruiting

Phoenix, Arizona, United States, 85032

Contacts

drzuniga@centerforneurologyandspine.com

Principal Investigator:

Leslie Zuniga

University of Connecticut Health Center - Department of Medicine

Recruiting

Farmington, Connecticut, United States, 06030-5550

Contacts

alhernandez@uchc.edu

Principal Investigator:

Amanda Hernandez

The George Washington University Medical Faculty Associates Foggy Bottom South Pavilion

Recruiting

Washington D.C., District of Columbia, United States, 20037

Contacts

hkaminski@mfa.gwu.edu

Principal Investigator:

Henry J Kaminski

Neurology of Central Florida Research Center, LLC

Recruiting

Altamonte Springs, Florida, United States, 32714

Contacts

neuroresearchcfl@gmail.com

Principal Investigator:

Alicia V Cabrera

SFM Clinical Research, LLC

Recruiting

Boca Raton, Florida, United States, 33487

Contacts

marc.feinberg@sfmresearch.com

Principal Investigator:

Marc H Feinberg

University of Florida Health Science Center - 300120311

Recruiting

Jacksonville, Florida, United States, 32209

Contacts

michael.pulley@jax.ufl.edu

Principal Investigator:

Michael T Pulley

Neurology Associates, P. A.

Recruiting

Maitland, Florida, United States, 32751

Contacts

adslansky@gmail.com

Principal Investigator:

Adam D Slansky

University of South Florida - PARENT - PARENT

Recruiting

Tampa, Florida, United States, 33612

Contacts

tvu6@usf.edu

Principal Investigator:

Tuan H Vu

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

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

mpasnoor@kumc.edu

Principal Investigator:

Mamatha Pasnoor

UNC Hospitals - PARENT

Recruiting

Chapel Hill, North Carolina, United States, 27599

Contacts

howardj@neurology.unc.edu

Principal Investigator:

James F Howard

Atrium Health Wake Forest Baptist

Recruiting

Winston-Salem, North Carolina, United States, 27157-1078

Contacts

rgandhi@wakehealth.edu

Principal Investigator:

Rachana B Gandhi Mehta

Miami Valley Hospital South

Recruiting

Centerville, Ohio, United States, 45459

Contacts

jpwilliams@premierhealth.com

Principal Investigator:

Jon P Williams

University of Cincinnati

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

hani.kushlaf@uc.edu

Principal Investigator:

Hani Kushlaf

Clinical Trials of South Carolina - Charleston

Recruiting

Charleston, South Carolina, United States, 29406

Contacts

dstickler@neurologycharleston.com

Principal Investigator:

David E Stickler

Erlanger Health, Inc. - 1123255

Recruiting

Chattanooga, Tennessee, United States, 37403

Contacts

chelsea.shugars@erlanger.org

Principal Investigator:

Chelsea A Shugars

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

Recruiting

Dallas, Texas, United States, 75246

Contacts

desirae.ransom@bswhealth.org

Principal Investigator:

Niloofar Yari

ANESC Research

Recruiting

El Paso, Texas, United States, 79912

Contacts

aherekarresearch@anesc.net

Principal Investigator:

Aamr A Herekar

Baylor Scott & White Neurology - McKinney

Recruiting

McKinney, Texas, United States, 75071

Contacts

francy.shu@bswhealth.org

Principal Investigator:

Francy Shu

The University of Vermont Medical Center

Recruiting

Burlington, Vermont, United States, 05401

Contacts

rup.tandan@uvmhealth.org

Principal Investigator:

Rup Tandan

Burnaby Hospital - Fraser Health Multiple Sclerosis Clinic

Recruiting

Burnaby, British Columbia, Canada, V5G 2X6

Contacts

marketa.vandenelzen@fraserhealth.ca

Principal Investigator:

Marketa Van den Elzen

More Information

Sponsor

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

Last update posted

Aug 12, 2026

Last verified

Aug, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-08. This information was provided to ClinicalTrials.gov by Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany on 2026-08-12.