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| Name | Class |
|---|---|
| Genentech, Inc. | INDUSTRY |
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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:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| 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 |
| 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. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Caterina Mainero, MD, PhD | Massachusetts General Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Massachusetts General Hospital | Charlestown | Massachusetts | 02129 | United States |
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Out of the 22 patients that signed the consent form, 2 patients became later ineligible to continue with the baseline study procedures.
22 patients signed the consent form.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
Patients with multiple sclerosis
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of study participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | 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. | Posted | Mean | Standard Deviation | SUVR | Baseline to 12 month |
|
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Respiratory, thoracic and mediastinal disorders | Systematic Assessment | Bronchopneumonia |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Covid-19 | Infections and infestations | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Caterina Mainero | Massachusetts General Hospital | 6177247746 | cmainero@mgh.harvard.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 5, 2023 | Nov 11, 2025 | Prot_SAP_001.pdf |
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| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
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| ID | Term |
|---|---|
| C526315 | (methyl-(11)C)N-acetyl-N-(2-methoxybenzyl)-2-phenoxy-5-pyridinamine |
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24 multiple sclerosis patients
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| 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 |
| Count of Participants |
| Participants |
|
| Age, Continuous | Age at baseline | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
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| Region of Enrollment | Number | participants |
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| Secondary | 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. | 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. | Posted | Mean | Standard Deviation | % of MTR | Baseline to 12-month |
|
|
|
|
| Secondary | Cortical Thickness | Secondary endpoint is changes in cortical thickness after 1-year ocrelizumab treatment in patients with multiple sclerosis. | A patient was excluded from the study analysis after it was discovered that they were using a medication not allowed by the study protocol. | Posted | Mean | Standard Deviation | mm2 | Baseline to 12-month |
|
|
|
|
| Secondary | White Matter (WM) Lesion Volume | Secondary endpoint is changes in WM lesion load after 1-year of ocrelizumab therapy in patients with MS. | A patient was excluded from the study analysis after it was discovered that they were using a medication not allowed by the study protocol. | Posted | Mean | Standard Deviation | mm cubic | Baseline to 12 months |
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| 0 |
| 20 |
| 1 |
| 20 |
| 12 |
| 20 |
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| Typical multiple sclerosis relapse | Nervous system disorders | Systematic Assessment |
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| Urinary infection | Infections and infestations | Systematic Assessment |
|
| Hiatal hernia | Gastrointestinal disorders | Systematic Assessment |
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| Pregnancy | Pregnancy, puerperium and perinatal conditions | Systematic Assessment |
|
| Ocrevus infusion reaction | Skin and subcutaneous tissue disorders | Systematic Assessment |
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| Urinary incontinence | Renal and urinary disorders | Systematic Assessment |
|
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| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Title | Measurements |
|---|---|
|
| 12-month cortical MTR |
|
| 0.024 |
| Other |
Paired-t test |