What side effects are associated with this type of intervention?

Common treatments for Multiple Sclerosis, particularly B-cell depleting therapies like ocrelizumab, can have several side effects. Ocrelizumab is generally well-tolerated but can cause infusion-related reactions, infections (including respiratory and herpes infections), and a potential increased risk of malignancies. Other disease-modifying therapies for MS, such as glatiramer acetate, may cause local injection site reactions, lipoatrophy, and systemic reactions like chest pain and palpitations. Fingolimod, another MS treatment, is associated with risks like macular edema, bradycardia, and increased susceptibility to infections. Patients should discuss these potential side effects with their healthcare provider to make informed treatment decisions.

What prior FDA approvals exist?

Ocrelizumab, approved by the FDA for the treatment of Multiple Sclerosis, works by depleting B-cells through targeting the CD20 protein. Another similar drug is rituximab, which also targets CD20 for B-cell depletion, although it is not specifically approved for MS but is used off-label. Other FDA-approved treatments for MS include interferon-beta formulations, glatiramer acetate, and newer oral medications like dimethyl fumarate and fingolimod, which have different mechanisms of action aimed at modulating the immune response.

What other types of research exist?

Promising, novel alternatives to higher dose ocrelizumab for Multiple Sclerosis patients include oral dimethyl fumarate (BG-12) and subcutaneous glatiramer acetate. Both have shown significant efficacy in reducing relapse rates and new brain lesions in clinical trials. Additionally, emerging therapies such as siponimod, ozanimod, and cladribine, which target different pathways in MS, may also be considered as potential alternatives.

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Monoclonal Antibodies

High-Dose Ocrelizumab for Multiple Sclerosis

Phase 3

Waitlist Available

Research Sponsored by Hoffmann-La Roche

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

Must not have

Any previous treatment with bone marrow transplantation and hematopoietic stem cell transplantation

Immunocompromised state

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to approximately 4.3 years

Awards & highlights

No Placebo-Only Group

Pivotal Trial

Summary

This trial is testing if a higher dose of ocrelizumab given through an IV drip is more effective and safe for patients with Primary Progressive Multiple Sclerosis (PPMS). The drug works by reducing harmful immune cells to potentially slow down the disease. Ocrelizumab is the first drug approved for treating both relapsing and primary progressive forms of multiple sclerosis.

Who is the study for?

Adults with Primary Progressive Multiple Sclerosis (PPMS) who have specific MRI brain abnormalities, a stable neurological condition for at least 30 days before the trial, and an EDSS score between 3 to 6.5. Disease duration must be under 10 years for lower EDSS scores or under 15 years for higher scores. Women of childbearing potential must use contraception; those without reproductive potential can also join.

What is being tested?

The study is testing whether a higher dose of Ocrelizumab given every six months is more effective than the approved standard dose in treating PPMS. It's randomized and double-blind, meaning participants are put into groups by chance and neither they nor the researchers know who gets which dose.

What are the potential side effects?

Ocrelizumab may cause infusion reactions, infections due to weakened immune response, possible reactivation of hepatitis B if previously infected, and increased risk of cancer as seen in some patients.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My disability score is between 3 and 6.5.

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My walking test score is 150 seconds or less.

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I have been diagnosed with primary progressive multiple sclerosis.

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I have been diagnosed with primary progressive multiple sclerosis.

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I have difficulty moving my legs.

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I have a mobility issue in my legs that affects my daily activities.

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My disability score is between 3 and 6.5.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have had a bone marrow or stem cell transplant.

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My immune system is weakened.

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I have not had IV immunoglobulin or plasmapheresis in the last 12 weeks.

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I have previously been treated with specific drugs like mitoxantrone or alemtuzumab.

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I cannot have an MRI or use gadolinium.

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I need long-term steroids or immunosuppressants for another condition.

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I am allergic or cannot take certain required medications for infusion reactions.

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I do not have good veins for IV access.

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I have stopped any previous immune-related treatments for the required time.

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I haven't taken fingolimod, siponimod, or ozanimod in the last 6 weeks.

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I have had an organ transplant or received anti-rejection medication.

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I have not taken corticosteroids in the last 4 weeks.

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I have or might have had a brain infection called PML.

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I have been treated with natalizumab within the last 4.5 months.

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My condition is either relapsing-remitting or secondary progressive MS.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to approximately 4.3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to approximately 4.3 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to approximately 4.3 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Time to onset of cCDP sustained for at least 12 weeks.

Secondary study objectives

Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the approved dose ocrelizumab group

Change in NfL (i.e. ratio to baseline) at Week 96 for patients in the higher dose ocrelizumab group

Change in NfL at Week 96

+7 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Experimental Treatment

Active Control

Group I: Ocrelizumab Higher DoseExperimental Treatment3 Interventions

Participants will be randomized to receive a minimum of 5 higher treatment doses (1200 mg or 1800 mg) of ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the double blind treatment (DBT) phase. During the optional open-label extension (OLE) phase, participants will continue with their assigned dose of ocrelizumab (either 1200 or 1800 mg) for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Group II: Ocrelizumab Approved DoseActive Control3 Interventions

Participants will be randomized to receive a minimum of 5 treatment doses of 600 mg ocrelizumab administered by intravenous (IV) infusion every 24 weeks in the DBT phase. During the optional OLE phase, participants will be offered a higher dose of ocrelizumab (either 1200 or 1800 mg), based on their body weight at OLE baseline, for approximately 96 weeks (4 doses in total). Mandatory methylprednisolone (or equivalent) and antihistaminic drug (e.g., diphenhydramine or equivalent) will be administered approximately 30-60 minutes prior to the start of each ocrelizumab infusion.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Ocrelizumab

2016

Completed Phase 4

~7260

Methylprednisolone

2015

Completed Phase 4

~2280

Antihistamine

2016

Completed Phase 3

~240

0 / 22Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Multiple Sclerosis (MS) treatments often target the immune system to reduce inflammation and slow disease progression. Ocrelizumab, a monoclonal antibody, depletes B-cells by targeting the CD20 surface marker, which is crucial because B-cells play a significant role in the autoimmune response that damages myelin in MS. This mechanism helps reduce the frequency of relapses and slows the progression of disability. Other common treatments include interferon beta, which modulates the immune response, and glatiramer acetate, which mimics myelin basic protein to divert the immune attack away from myelin. These treatments are essential for MS patients as they help manage symptoms, reduce relapses, and improve quality of life.

Prognostic Markers of Ocrelizumab Effectiveness in Multiple Sclerosis: A Real World Observational Multicenter Study.