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

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. 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. 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. To explore whether changes in functional and structural imaging metrics under ocrelizumab are associated with changes in clinical outcome measures.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: 11C-PBR28

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Charlestown, Massachusetts, United States, 02129
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Hypersensitivity to trial medications
2. History of life-threatening reaction to Ocrelizumab
3. Acute or uncontrolled chronic medical condition
4. Impaired hearing
5. Claustrophobia
6. 300 lbs of greater (weight limit of MRI table)
7. Pregnancy or breastfeeding
8. Sensitivity to imaging agents
9. Contraindications to MRI
10. Use of benzodiazepines, topiramate, doxycycline, mynocicline

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multiple sclerosis patients; 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; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Magnetization Transfer Ratio (MTR)	Secondary endpoint is changes in mean magnetization transfer ratio (MTR) in cortex and normal appearing white matter (NAWM) of multiple sclerosis patients after 1-year of ocrelizumab therapy. MTR is defined as: S0 - S_MT/S0; where S0 is the signal intensity without the magnetization transfer (MT) pulse and S_MT is the signal intensity with the MT pulse. It is dimensionless because it is defined as a ratio of two signals with the same physical units, so the units cancel out. Larger MTR indicate stronger interaction between free water protons and macromolecular-bound protons.	Baseline to 12-month
Cortical Thickness	Secondary endpoint is changes in cortical thickness after 1-year ocrelizumab treatment in patients with multiple sclerosis.	Baseline to 12-month
White Matter (WM) Lesion Volume	Secondary endpoint is changes in WM lesion load after 1-year of ocrelizumab therapy in patients with MS.	Baseline to 12 months

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Genentech, Inc.
• Investigators: Principal Investigator: Caterina Mainero, MD, PhD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2020
• Primary Completion (Actual): October 9, 2024
• Study Completion (Actual): April 30, 2025

Study Registration Dates

• First Submitted: January 13, 2020
• First Submitted That Met QC Criteria: January 13, 2020
• First Posted (Actual): January 18, 2020

Study Record Updates

• Last Update Posted (Actual): December 30, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine
• Other Study ID Numbers: 2019P002865

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No