Trial Outcomes & Findings for Effect of Ocrelizumab on Neuroinflammation in Multiple Sclerosis as Measured by 11C-PBR28 MR-PET Imaging of Microglia Activation (NCT NCT04230174)

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

22 participants

Primary outcome timeframe

Baseline to 12 month

Results posted on

2025-12-30

Participant Flow

22 patients signed the consent form.

Out of the 22 patients that signed the consent form, 2 patients became later ineligible to continue with the baseline study procedures.

Participant milestones

Participant milestones
Measure	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. This study will evaluate, serially, functional and structural tissue changes in the cortex and brain white matter (lesions and normal appearing white matter) of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.
Overall Study STARTED	20
Overall Study COMPLETED	15
Overall Study NOT COMPLETED	5

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Multiple Sclerosis Patients n=20 Participants Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. This study will evaluate, serially, functional and structural tissue changes in the cortex and brain white matter (lesions and normal appearing white matter) of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.
Age, Categorical <=18 years	0 Participants n=174 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=174 Participants
Age, Categorical >=65 years	0 Participants n=174 Participants
Age, Continuous	43.15 years STANDARD_DEVIATION 12.7 • n=174 Participants
Sex: Female, Male Female	18 Participants n=174 Participants
Sex: Female, Male Male	2 Participants n=174 Participants
Race/Ethnicity, Customized White	18 Participants n=174 Participants
Race/Ethnicity, Customized Black/African American	1 Participants n=174 Participants
Race/Ethnicity, Customized Hispanic	1 Participants n=174 Participants
Region of Enrollment United States	20 participants n=174 Participants

PRIMARY outcome

Timeframe: Baseline to 12 month

Population: Fifteen MS patients completed the follow-up MR-PET study, which was performed at an average interval of 19.8 days (SD=22.6) after receiving the 1-year ocrelizumab dose. A patient was excluded from the PET analysis after it was discovered that they were using a medication not allowed by the study protocol.

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

Outcome measures

Outcome measures
Measure	Multiple sclerosis patients n=14 Participants Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. 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.
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) Baseline SUVR in perilesional white matter	0.9 SUVR Standard Deviation 0.19
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) Baseline SUVR in white matter lesions	0.9 SUVR Standard Deviation 0.21
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) Baseline SUVR in thalamus	1.31 SUVR Standard Deviation 0.26
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) 12-month SUVR in perilesional white matter	0.84 SUVR Standard Deviation 0.19
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) 12-month SUVR in white matter lesions	0.83 SUVR Standard Deviation 0.2
11C-PBR28 Uptake as Measured by Standardized Uptake Values Normalized by a Pseudoreference Region (SUVR) 12-month SUVR in thalamus	1.23 SUVR Standard Deviation 0.25

SECONDARY outcome

Timeframe: Baseline to 12-month

Population: Longitudinal MTR scans were acquired in 15 patients; in one subject, however, the MT\_off acquisition was not completed due to early scan termination as the subject was unable to tolerate the scan duration. MTR maps from another subject were excluded from the group analysis due to severe motion artifacts.

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.

Outcome measures

Outcome measures
Measure	Multiple sclerosis patients n=13 Participants Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. 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.
Magnetization Transfer Ratio (MTR) 12-month cortical MTR	16.8 % of MTR Standard Deviation 1.1
Magnetization Transfer Ratio (MTR) Baseline NAWM MTR	27.9 % of MTR Standard Deviation 1.4
Magnetization Transfer Ratio (MTR) Baseline cortical MTR	17.3 % of MTR Standard Deviation 0.9
Magnetization Transfer Ratio (MTR) 12-month NAWM MTR	27.0 % of MTR Standard Deviation 1.9

SECONDARY outcome

Timeframe: Baseline to 12-month

Population: A patient was excluded from the study analysis after it was discovered that they were using a medication not allowed by the study protocol.

Secondary endpoint is changes in cortical thickness after 1-year ocrelizumab treatment in patients with multiple sclerosis.

Outcome measures

Outcome measures
Measure	Multiple sclerosis patients n=14 Participants Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. 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.
Cortical Thickness Baseline cortical thickness	2.35 mm2 Standard Deviation 0.09
Cortical Thickness 12-month cortical thickness	2.35 mm2 Standard Deviation 0.07

SECONDARY outcome

Timeframe: Baseline to 12 months

Population: A patient was excluded from the study analysis after it was discovered that they were using a medication not allowed by the study protocol.

Secondary endpoint is changes in WM lesion load after 1-year of ocrelizumab therapy in patients with MS.

Outcome measures

Outcome measures
Measure	Multiple sclerosis patients n=14 Participants Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. 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.
White Matter (WM) Lesion Volume Baseline white matter lesion volume	6248 mm cubic Standard Deviation 7314
White Matter (WM) Lesion Volume 12-month white matter lesion volume	6021 mm cubic Standard Deviation 6821

Adverse Events

Multiple Sclerosis Patients

Serious events: 1 serious events

Other events: 12 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Multiple Sclerosis Patients n=20 participants at risk Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. This study will evaluate, serially, functional and structural tissue changes in the cortex and brain white matter (lesions and normal appearing white matter) of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.
Respiratory, thoracic and mediastinal disorders Pneumonia	5.0% 1/20 • Number of events 1 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.

Other adverse events

Other adverse events
Measure	Multiple Sclerosis Patients n=20 participants at risk Multiple sclerosis patients will be evaluated with 11C-PBR28 MR-PET at baseline before and at 12 month follow up after Ocrelizumab therapy. This study will evaluate, serially, functional and structural tissue changes in the cortex and brain white matter (lesions and normal appearing white matter) of subjects with RRMS and progressive disease under Ocrelizumab using 11C-PBR28 MR-PET imaging at baseline and at approximately 12-month follow up.
Infections and infestations Covid-19	20.0% 4/20 • Number of events 4 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Nervous system disorders Typical multiple sclerosis relapse	10.0% 2/20 • Number of events 2 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Infections and infestations Urinary infection	5.0% 1/20 • Number of events 1 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Gastrointestinal disorders Hiatal hernia	5.0% 1/20 • Number of events 1 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Pregnancy, puerperium and perinatal conditions Pregnancy	5.0% 1/20 • Number of events 1 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Skin and subcutaneous tissue disorders Ocrevus infusion reaction	10.0% 2/20 • Number of events 2 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.
Renal and urinary disorders Urinary incontinence	5.0% 1/20 • Number of events 1 • The study period during which all AE are reported begins after informed consent is obtained and initiation of study treatment and ends 30 days following the last administration of radiotracer and MR-PET or study discontinuation/termination, whichever is earlier, approximately up to 14-15 months.

Additional Information

Caterina Mainero

Massachusetts General Hospital

Phone: 6177247746

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place