Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation

NCT04230174 | Completed Phase 4 Results FDA Drug

• 1 other identifier: 2019P002865
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Using magnetic resonance-PET (MR-PET) imaging with \[11C\]PBR28, a second-generation 18kDa translocator protein (TSPO) radiotracer, we have previously demonstrated abnormally high TSPO expression, indicative of microglia activation, across different brain tissue compartments of multiple sclerosis (MS) patients1. In this study, we propose to study the efficacy of ocrelizumab, a humanized monoclonal antibody that has been shown to decrease neuroinflammation in relapsing-remitting multiple sclerosis (RRMS) and progressive multiple sclerosis (MS) patients. We will test these effects by studying a cohort of 24 MS patients (12 RRMS, 12 progressive MS). Participants will be studied before (within 3 months prior to initiating treatment) and after treatment with ocrelizumab (\~12 month follow up), a therapeutic drug that will be part of their standard medical care. We will use \[11C\]PBR28 to help determine changes in neuroinflammation. The purpose of this study is to determine the effects of ocrelizumab treatment on neuroinflammation by analyzing the uptake and distribution of \[11C\]PBR28 in individuals with multiple sclerosis. The specific aims of the current study are:

1. 1.To assess whether treatment with ocrelizumab in subjects with either relapsing-remitting MS or progressive MS is associated with decreased \[11C\]PBR28 binding in the cortex and white matter (lesions and normal appearing white matter), suggesting reduced neuroinflammation.
2. 2.To assess whether changes in neuroinflammation under ocrelizumab treatment, as measured by \[11C\]PBR28 uptake at 12-month follow up relative to baseline, are associated with changes in structural MR metrics of brain tissue damage including white matter lesion load, cortical atrophy, and demyelination in the cortex and in the normal-appearing white matter as measured by magnetization transfer ratio (MTR).
3. 3.To explore whether changes in functional and structural imaging metrics under ocrelizumab are associated with changes in clinical outcome measures.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (1)

• 11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR)

  The primary endpoint is change in mean 11C-PBR28 SUVR in multiple sclerosis patients after 1-year of ocrelizumab therapy in different brain regions.

  Baseline to 12 month

Secondary Outcomes (3)

• Magnetization Transfer Ratio (MTR)

  Baseline to 12-month

• Cortical Thickness

  Baseline to 12-month

• White Matter (WM) Lesion Volume

  Baseline to 12 months

Study Arms (1)

Multiple sclerosis patients

EXPERIMENTAL

Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy.

Drug: 11C-PBR28

Interventions

11C-PBR28 DRUG

This study will evaluate, serially, functional and structural tissue changes in the cortex and WM of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.

Multiple sclerosis patients

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• RRMS and/or PMS subtype
• EDSS between 0 and 7.0
• Express at least one high-affinity (Ala147) allele of the TSPO receptor for PBR28
• Initiating Ocrelizumab treatment within the next 3 months

You may not qualify if:

• Hypersensitivity to trial medications
• History of life-threatening reaction to Ocrelizumab
• Acute or uncontrolled chronic medical condition
• Impaired hearing
• Claustrophobia
• lbs of greater (weight limit of MRI table)
• Pregnancy or breastfeeding
• Sensitivity to imaging agents
• Contraindications to MRI
• Use of benzodiazepines, topiramate, doxycycline, mynocicline

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Massachusetts General Hospital

Charlestown, Massachusetts, 02129, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

(methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Results Point of Contact

• Title: Caterina Mainero
• Organization: Massachusetts General Hospital

cmainero@mgh.harvard.edu

6177247746

Study Officials

• Caterina Mainero, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: 24 multiple sclerosis patients

Study Record Dates

• First Submitted: January 13, 2020
• First Posted: January 18, 2020
• Study Start: December 29, 2020
• Primary Completion: October 9, 2024
• Study Completion: April 30, 2025
• Last Updated: December 30, 2025
• Results First Posted: December 30, 2025

Record last verified: 2025-12

Locations

US (1)