NCT04767698

Addition of Belimumab to B-cell Depletion in Relapsing-remitting Multiple Sclerosis

Addition of Belimumab to B-cell Depletion to Produce Prolonged Remission of Relapsing-remitting Multiple Sclerosis Disease Activity

• Status: Terminated
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 4 (actual)
• Sponsor: Johns Hopkins University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

Multiple sclerosis is the most common inflammatory disease of the central nervous system and a common cause of disability in young adults. Depleting B cells from the circulation with an anti-cluster of differentiation (CD) 20 antibodies has proven to be an effective strategy in reducing relapses and disability in patients with the relapsing-remitting disease. However, continuous and long-term depletion of B-cells can result in reduced immunoglobulin levels, immunosuppression, and an increased tendency for severe infections and perhaps, even malignancy. Blocking B-cell Activating Factor (BAFF) is effective for the treatment of several autoimmune disorders. Belimumab, a BAFF blocking antibody, has been approved by the Food and Drug Administration for the treatment of systemic lupus erythematosus. Belimumab has been shown to have immunomodulatory properties, without resulting in overt immunosuppression. The investigators hypothesize that belimumab, given to patients who received a short course of treatment with B-cell depleting antibody (ocrelizumab), will be safe and equally effective in reducing MS disease activity (as compared to patients receiving continuous treatment with ocrelizumab); while resulting in less immunosuppression, as measured by antibody response to pneumococcal vaccination. Currently, available treatment strategies in relapsing MS sacrifice higher efficacy for long-term safety or vice versa. The proposed strategy in this application combines the long-term safety and high efficacy to treat patients with relapsing-remitting multiple sclerosis (RRMS) and, if eventually proven effective, can be adopted in a large proportion of patients with this chronic disease. This is a randomized, open-labeled trial. Forty eligible participants will be randomized 1:1 to either receiving a form of standard of care, ocrelizumab (300 mg two infusions two weeks apart at baseline and then 600 mg as a single infusion every six months) or belimumab (200 mg subcutaneous (SC) weekly for 36 months) plus two courses of ocrelizumab (300 mg two infusions two weeks apart at baseline and 600 mg as a single infusion six months later). Co-primary outcomes of the study include pneumococcal vaccine antibody response, the return of MS disease activity, and proportions of patients with adverse events and serious adverse events.

Conditions

• Multiple Sclerosis

Interventions

Type	Name	Description
DRUG	Belimumab	200 mg SC weekly for 36 months
DRUG	Short-course Ocrelizumab	300 mg, two infusions two weeks apart and then 600 mg as a single infusion after six months (only one time) (total of two courses of treatment)
DRUG	Continued Ocrelizumab	300 mg, two infusions two weeks apart and then 600 mg as a single infusion every six months for a total of 36 months

Timeline

• Start date: 2021-10-01
• Primary completion: 2022-05-10
• Completion: 2022-05-10
• First posted: 2021-02-23
• Last updated: 2023-03-07
• Results posted: 2023-03-07

Locations

1 site across 1 country: United States

Regulatory

• FDA-regulated drug study