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 Primary Progressive Multiple Sclerosis

  • End date
    Nov 14, 2028
  • participants needed
  • sponsor
    Hoffmann-La Roche
Updated on 27 October 2022
brain mri
disease or disorder
oligoclonal bands


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 PPMS, in comparison to the approved 600 mg dose of ocrelizumab.


Participants will be treated for a minimum of 120 weeks in the double-blind phase. Upon positive primary results after the double-blind phase, an optional higher dose extension treatment (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 lower limit 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 lower limit of normal.

Condition Multiple Sclerosis
Treatment Methylprednisolone, Ocrelizumab, Antihistamine
Clinical Study IdentifierNCT04548999
SponsorHoffmann-La Roche
Last Modified on27 October 2022


Yes No Not Sure

Inclusion Criteria

Diagnosis of primary progressive multiple sclerosis (PPMS)
Expanded disability status scale (EDSS) score at screening and baseline, from 3 to 6.5 inclusive
Average T25FWT score over two trials at screening and over two trials at baseline respectively, up to 150 (inclusive) seconds
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
Average 9HPT score over four trials (two trials with each hand) at screening and over four trials (two trials with each hand) at baseline respectively, up to 250 (inclusive) seconds
Participants must be neurologically stable for at least 30 days prior to randomization and baseline
Score of >/= to 2.0 on the Functional Systems scale for the pyramidal system that was due to lower extremity findings at screening and baseline
Documented MRI of brain with abnormalities consistent with MS
For females of childbearing potential, agreement to remain abstinent or use adequate contraceptive methods
For female participants without reproductive potential, may be enrolled if post-menopausal unless receiving a hormonal therapy for her menopause or if surgically sterile
Disease duration from the onset of MS symptoms; if EDSS score at screening is less or equal to 5, disease duration must be less than 10 years; If EDSS score at screening is more than 5, disease duration must be less than 15 years
Documented evidence of the presence of at least one cerebrospinal fluid-specific oligoclonal bands

Exclusion Criteria

History of relapsing remitting or secondary 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
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
Known presence of other neurologic disorders that could interfere with the diagnosis of MS or assessments of efficacy and/or safety during the study
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 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
Any previous treatment with mitoxantrone, cladribine, atacicept, alemtuzumab, and daclizumab
Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation
Any previous history of transplantation or anti-rejection therapy
Previous treatment with fingolimod, siponimod, or ozanimod within 6 weeks of baseline
Treatment with intravenous (IV) immunoglobulin (Ig) or plasmapheresis within 12 weeks prior to randomization
Previous treatment with natalizumab within 4.5 months of baseline
Systemic corticosteroid therapy within 4 weeks prior to screening
Previous treatment with interferons beta (1a or 1b), or glatiramer acetate within 2 weeks of baseline
Positive screening tests for active, latent, or inadequately treated hepatitis B
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 additional exclusionary criterion as per ocrelizumab local label, if more stringent than the above
Sensitivity or intolerance to any ingredient (including excipients) of ocrelizumab
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer  to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact


Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider


Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 



Reply by • Private

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note