Resumen

Estudio aleatorizado, doble ciego, controlado, de grupos paralelos y multicéntrico para evaluar la eficacia, seguridad y farmacocinética (FK) de una dosis más alta de ocrelizumab por infusión intravenosa (IV) cada 24 semanas (Q24W) en participantes con EMR, en comparación con la dosis aprobada de 600 miligramos (mg) de ocrelizumab.

Descripción detallada

Los participantes serán tratados durante un mínimo de 120 semanas en la fase de tratamiento doble ciego (TDC). Ante resultados primarios positivos después de la fase TDC, se planea una fase opcional de tratamiento a dosis más alta en extensión abierta (OLE) para los participantes elegibles. La OLE se llevará a cabo durante aproximadamente 96 semanas. Posteriormente, los participantes serán seguidos para vigilancia de seguridad durante 48 semanas. Los participantes cuyos niveles de linfocitos B no se hayan recuperado a su nivel basal ni al límite inferior de la normalidad (LIN), el que sea menor, pasarán a la fase de monitorización de linfocitos B (MLB) tras la fase de seguimiento de seguridad. El estudio finalizará cuando todos los participantes que no hayan recibido una terapia alternativa deplectora de linfocitos B hayan recuperado sus linfocitos B al valor basal o al LIN.

Elegibilidad

Edad mínima: 18 YearsEdad máxima: 55 YearsSexo: ALL

Criterios de inclusión

Diagnosis of RMS
At least two documented clinical relapses within the last 2 years prior to screening, or one clinical relapse in the year prior to screening. No relapse 30 days prior to screening and at baseline
Participants must be neurologically stable for at least 30 days prior to randomization and baseline
EDSS score, at screening and baseline, from 0 to 5.5 inclusive
Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
Average 9HPT score over four trials at screening and over four trials at baseline respectively, up to 250 (inclusive) seconds
Documented magnetic resonance imaging (MRI) of brain with abnormalities consistent with MS at screening
Participants requiring symptomatic treatment for MS and/or physiotherapy must be treated at a stable dose. No initiation of symptomatic treatment for MS or physiotherapy within 4 weeks of randomization
Females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods
Female participants without reproductive potential may be enrolled e.g. if post-menopausal or if surgically sterile

Criterios de exclusión

History of primary progressive MS at screening
Any known or suspected active infection at screening or baseline (except nailbed infections), or any major episode of infection requiring hospitalization or treatment with IV antimicrobials within 8 weeks or treatment with oral antimicrobials within 2 weeks, prior to and during screening
History of confirmed or suspected progressive multifocal leukoencephalopathy
History of cancer, including hematologic malignancy and solid tumors, within 10 years of screening
Immunocompromised state
Receipt of a live or live-attenuated vaccine within 6 weeks prior to randomization
Inability to complete an MRI or contraindication to gadolinium administration
Contraindications to mandatory pre-medications for infusion-related reaction (IRRs)
Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
Any concomitant disease that may require chronic treatment with systemic corticosteroids or immunosuppressants during the course of the study
Significant, uncontrolled disease that may preclude participant from participating in the study
History of or currently active primary or secondary, non-drug-related, immunodeficiency
Pregnant or breastfeeding or intending to become pregnant
Lack of peripheral venous access
History of alcohol or other drug abuse within 12 months prior to screening
Treatment with any investigational agent within 24 weeks prior to screening or treatment with any experimental procedure for MS
Previous use of anti- cluster of differentiation 20 (CD20s) (including ocrelizumab), unless the last infusion was more than 2 years before screening, B-cell count is normal, and the stop of the treatment was not motivated by safety reasons or lack of efficacy
Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
Previous treatment with natalizumab within 4.5 months of baseline
Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab - Previous treatment with any other immunomodulatory or immunosuppressive medication not already listed above without appropriate washout as described in the applicable local label. If the washout requirements are not described in the applicable local label, then the wash out period must be five times the half-life of the medication
Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
Any previous history of transplantation or anti-rejection therapy
Treatment with IV immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
Systemic corticosteroid therapy within 4 weeks prior to screening
Positive screening tests for active, latent, or inadequately treated hepatitis B
Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
Any additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above

Intervenciones

drug

Ocrelizumab

The actual higher dose of ocrelizumab will be assigned to participants based on their body weight at baseline: 1200 mg (body weight \<75 kg) or 1800 mg (body weight ≥ 75 kg). The first dose of ocrelizumab will be administered as two 600 mg or 900 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 1200 mg or 1800 mg IV infusion Q24W. During the optional OLE phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total).

drug

Ocrelizumab

Ocrelizumab will be administered at a dose of 600 mg Q24W. The first dose of ocrelizumab will be administered as two 300 mg IV infusions given 14 days apart. For the subsequent doses, ocrelizumab will be administered as a single 600 mg IV infusion Q24W.

drug

Antihistamine

Premedication with oral or IV antihistaminic drug (i.e., diphenhydramine 50 mg or an equivalent dose of an alternative) will be administered prior to each ocrelizumab infusion.

drug

Methylprednisolone

Premedication with 100 mg of methylprednisolone (or equivalent) will be administered by IV infusion prior to each ocrelizumab infusion.

Estudio de fase IIIb, multicéntrico, aleatorizado, doble ciego, controlado para evaluar la eficacia, seguridad y farmacocinética de una dosis más alta de ocrelizumab en adultos con esclerosis múltiple remitente recurrente.

Resumen

Descripción detallada

Elegibilidad

Criterios de inclusión

Criterios de exclusión

Intervenciones

Ocrelizumab

Ocrelizumab

Antihistamine

Methylprednisolone

Ubicaciones

Centro de Especialidades Neurológicas y Rehabilitación - CENyR

CEMIC

Centro de Investigaciones Médicas Tucuman

Patrocinadores