Resumen

El propósito de este estudio clínico es determinar la eficacia y seguridad de una nueva formulación de cladribina oral en participantes con miastenia gravis generalizada (gMG) en comparación con placebo. También investigará la eficacia sostenida, la necesidad de retratamiento y la seguridad a largo plazo de la cladribina oral en gMG. Se incluye un componente adicional para caracterizar la farmacocinética (FK) de la nueva formulación de cladribina en participantes con gMG. Este estudio se divide en 3 períodos: el período pivotal de control doble ciego con placebo (DBPC) y 2 extensiones: la extensión ciega (EC) y el período de retratamiento (RT).

Elegibilidad

Edad mínima: 18 YearsSexo: ALL

Criterios de inclusión

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

Criterios de exclusión

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

Intervenciones

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.

Ubicaciones

Expertia S.A- Mautalen Salud e Investigación

Ciudad Autonoma Buenos Aires, Argentina

RECRUITING

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

Ciudad Autonoma Buenos Aires, Argentina

RECRUITING

Instituto de Investigaciones Metabolicas (IDIM)

Ciudad Autonoma Buenos Aires, Argentina

RECRUITING

Hospital Cordoba

Córdoba, Argentina

RECRUITING

Fundacion Rosarina de Neurorehabilitacion

Rosario, Argentina

RECRUITING

INECO Neurociencias Oroño

Rosario, Argentina

RECRUITING

CER San Juan Centro Polivalente de Asistencia e Inv. Clinica

San Juan, Argentina

RECRUITING

Centro de Investigaciones Medicas Tucuman

San Miguel de Tucumán, Argentina

RECRUITING

Estudio de fase 3, aleatorizado, doble ciego, controlado con placebo, de 3 brazos y 3 períodos para evaluar la eficacia y seguridad de una nueva formulación de cladribina oral en comparación con placebo en participantes con miastenia gravis generalizada (MyClad)

Resumen

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Placebo

Cladribine Low Dose

Cladribine High Dose

Ubicaciones

Expertia S.A- Mautalen Salud e Investigación

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

Instituto de Investigaciones Metabolicas (IDIM)

Hospital Cordoba

Fundacion Rosarina de Neurorehabilitacion

INECO Neurociencias Oroño

CER San Juan Centro Polivalente de Asistencia e Inv. Clinica

Centro de Investigaciones Medicas Tucuman

Patrocinadores

Contactos

US Medical Information

Communication Center