A Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis (RMS)


Trial ID: NCT04544436


This is a randomized, double blind, controlled, parallel group, multicenter study to evaluate efficacy, safety and pharmacokinetics of a higher dose of ocrelizumab per intravenous (IV) infusion every 24 weeks in participants with RMS, in comparison to the approved 600 mg dose of ocrelizumab.

Official Title

A Phase IIIb Multicenter, Randomized, Double-Blind, Controlled Study to Evaluate the Efficacy, Safety and Pharmacokinetics of a Higher Dose of Ocrelizumab in Adults With Relapsing Multiple Sclerosis

Stanford Investigator(s)

Lucas Kipp
Lucas Kipp

Clinical Associate Professor, Neurology & Neurological Sciences


Inclusion Criteria:

   - Diagnosis of relapsing multiple sclerosis (RMS) (i.e., RRMS or aSPMS where
   participants still experience relapses) in accordance with the revised McDonald
   Criteria 2017

   - 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.

   - Expanded disability status scale (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 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 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,

   - 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-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

   - 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

   - Any previous history of transplantation or anti-rejection therapy.

   - Treatment with intravenous (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.


drug: Ocrelizumab

drug: Ocrelizumab

drug: Antihistamine

drug: Methylprednisolone


Contact Information

Stanford University
School of Medicine
300 Pasteur Drive
Stanford, CA 94305