a study to evaluate the efficacy, safety and pharmacokinetics (pk) of a higher dose of ocrelizumab in adults with relapsing multiple sclerosis (rms)

Conditions: Multiple Sclerosis

Summary: this is a randomized, double-blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and pk of a higher dose of ocrelizumab per intravenous (iv) infusion every 24 weeks (q24w) in participants with rms, in comparison to the approved 600 milligrams (mg) dose of ocrelizumab.

participants will be treated for a minimum of 120 weeks in the double-blind treatment (dbt) phase. upon positive primary results after the dbt phase, an optional higher dose extension treatment, open-label extension (ole) phase is planned for eligible participants. the ole will be carried out for approximately 96 weeks. participants will be followed for safety for 48 weeks thereafter. participants whose b-cell levels still did not replete to their baseline level or the low level of normal (lln), whichever is lower, will move into the b-cell monitoring (bcm) phase following the safety follow-up phase. the study will end when all participants who were not treated with an alternative b-cell depleting therapy have repleted their b-cells to the baseline value or the lln.

Eligibility criteria:
inclusion criteria: * 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 exclusion criteria: * 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

Keywords: relapsing remitting multiple sclerosis; higher dose of cd20 antibody ocrelizumab; efficacy, safety and pharmacokinetics