Ocrelizumab for Preventing Clinical Multiple Sclerosis in Individuals With Radiologically Isolated Disease.

Phase 4

Terminated

• Conditions: Multiple Sclerosis; Radiologically Isolated Syndrome
• Interventions: Other: Placebo; Drug: Ocrelizumab

• Registration Number: NCT04877457
• Lead Sponsor: Yale University

Brief Summary

This is a multicenter, randomized, double-blind, placebo-controlled, Phase 4 study in which eligible patients with RADIOLOGICALLY ISOLATED SYNDROME (RIS) (as defined by meeting 2017 McDonald criteria for DIS) will be randomized 1:1 to receive ocrelizumab treatment or placebo (standard of care).

Detailed Description

This study is designed to investigate the treatment effect of ocrelizumab compared with placebo on clinical and radiological outcomes in patients with RIS (i.e., asymptomatic CNS lesions fulfilling the 2017 McDonald criteria for DIS), as well as neuroimaging, serologic, immunologic and other exploratory biomarkers of MS disease biology in order to improve the understanding of B cell biology in early disease pathophysiology, characterize the emergence of CNS autoimmunity, and the mechanism of action of ocrelizumab in this population.

Study Timeline

• Study First Submitted: 2021-04-30
• Study First Submitted QC: 2021-05-03
• Study First Posted: 2021-05-07
• Study Start: 2022-02-15
• Primary Completion: 2023-06-12
• Study Completion: 2023-06-12
• Results First Submitted: 2024-06-10
• Status Verified: 2024-10
• Results First Submitted QC: 2024-10-01
• Last Update Submitted: 2024-10-01
• Results First Posted: 2024-10-09
• Last Update Posted: 2024-10-09

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 3

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Three courses of placebo will be administered over the course of the study.
Ocrelizumab	Ocrelizumab	Three courses of ocrelizumab will be administered over the course of the study.

Primary Outcome Measures

Name	Time	Method
Time to Development of First New Radiologic or Clinical Evidence of MS	Up 4 years	The primary efficacy endpoint for this study is to evaluate the efficacy of ocrelizumab compared with placebo on delaying the time to development of new radiological or clinical evidence of MS, defined as the time from baseline to first new T1 gadolinium-enhancing lesions and/or new or enlarging T2 lesions consistent with MS in participants OR first clinical evidence of MS, i.e., neurological event resulting from CNS demyelination as evidenced by acute or progressive clinical syndrome consistent with MS in participants.

Secondary Outcome Measures

Name	Time	Method
Cumulative Number of New or Enlarging T2 Lesions	Up to 4 years	MRI scans will be used to determine the number of new or enlarging T2 lesions
Change in T2-lesion Volume	Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks	MRI scans will be used to the change in T2 lesions
Cumulative Number of New T1 Gadolinium-enhancing Lesions	Up to 4 years	MRI scans will be used to determine the cumulative number of new T1 gadolinium-enhancing lesions
Change in Total Brain Volume	Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks	MRI scan will be used to determine the change in total brain volume
Change in Total Spinal Cord Volume	Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 156 weeks, 208 weeks	MRI scan will be used to determine the change in total brain volume
Change in Serum NfL (sNfL)	Baseline, 24 weeks, 48 weeks, 72 weeks, 104 weeks, 130 weeks, 156 weeks, 182 weeks, 208 weeks	Change in serum Nfl will be used measured

Trial Locations

Locations (4)

Cleveland Clinic Melen Center; 🇺🇸 Cleveland, Ohio, United States

Yale University; 🇺🇸 North Haven, Connecticut, United States

Icahn School of Medicine at Mount Sinai; 🇺🇸 New York, New York, United States

Oklahoma Medical Research Foundation; 🇺🇸 Oklahoma City, Oklahoma, United States