Ocrelizumab for Multiple Sclerosis

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Johns Hopkins University

Must be taking: Injectable DMTs

Must not be taking: Steroids, B-cell depleting antibodies

Disqualifiers: Hepatitis B, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

10 Participants Needed

Trial Summary

What is the purpose of this trial?

B-cells have an important role in the pathogenesis of multiple sclerosis (MS). Ocrelizumab, a medication that targets B-cells have been found to be highly effective in stopping the disease activity in relapsing-remitting MS. The efficacy of ocrelizumab might be related to the specific pattern of B-cell tolerance defect in patients with MS and the potential of its normalization with treatment with ocrelizumab. By analyzing the reactivity of recombinant antibodies expressed from single B-cells, the investigators' collaborators have demonstrated that the pattern of B-cell tolerance defect is different in people with MS who only display an impaired removal of developing autoreactive B-cells in the periphery while central B-cell tolerance in the bone marrow is functional in most patients. In contrast, patients with rheumatoid arthritis (RA), type-1 diabetes (T1D) or Sjögren's syndrome (SS) show defective central and peripheral B-cell tolerance checkpoints. As a consequence, while anti-B-cell therapy does not correct defective early B-cell tolerance checkpoints in T1D and only temporarily slows down autoimmune processes before newly generated autoreactive B-cells likely induce patient relapse, the investigators postulate that the efficacy of ocrelizumab in MS may be linked to normal central B-cell tolerance and the production of a normal B-cell and T-cell compartment after ocrelizumab therapy. In an open-label study, 10 patients with relapsing MS will be treated with two courses of ocrelizumab and will be followed clinically and radiologically for at least two and a half years. Assessment of T and B-cell phenotypes and function at baseline and 18-24 months post-B-cell depletion will be the primary outcome of the study.

Research Team

Bardia Nourbakhsh

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for people with relapsing-remitting multiple sclerosis (RRMS) who have an EDSS score of 3 or less, are not pregnant, and agree to use effective contraception. They must have recent MRI changes indicative of MS activity but can't join if they're allergic to ocrelizumab, previously used certain MS drugs or treatments, are pregnant/lactating, or have active hepatitis B.

Inclusion Criteria

I have been diagnosed with relapsing-remitting MS.

Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of <1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 24 weeks after the last dose of study treatment

My disability level is low, with a score of 3 or less.

Exclusion Criteria

I have received treatments that target B-cells or had a stem-cell transplant.

I cannot receive CD20 antibody treatment due to health reasons.

I have not taken steroids in the last 30 days.

Treatment Details

Interventions

• Ocrelizumab

Trial Overview The study tests Ocrelizumab's effect on B-cell tolerance defects in RRMS patients. It involves treating participants with two courses of the drug and monitoring them clinically and through MRIs for over two years to see how their immune cells behave post-treatment.

Participant Groups

Group I: Ocrelizumab Experimental Treatment 1 Intervention

Patients will be treated with two courses of ocrelizumab (Ocrevus) for one year and then will stop the medication and will be monitored for the return of the disease activity. Those who experience the return of the disease activity can go back on the medication.

Ocrelizumab is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in European Union as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Approved in Canada as Ocrevus for:

• Primary progressive multiple sclerosis
• Relapsing forms of multiple sclerosis

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Genentech, Inc.

Industry Sponsor

Trials

1,578

Recruited

569,000+

Ashley Magargee

Genentech, Inc.

Chief Executive Officer since 2024

MBA from Harvard University, BA from Princeton University

Levi Garraway

Genentech, Inc.

Chief Medical Officer since 2021

MD, PhD