Investigation of the Effect of Ocrelizumab on Peripheral Lymphocyte Immunophenotypes With Suppressive Capacity in MS

Study Overview
=================
Brief Summary
-----------------
This is a 24-month, prospective, exploratory, observational study to investigate immune phenotypes in patients with MS following treatment with ocrelizumab.

Detailed Description
-----------------
This is a 24-month, prospective, exploratory, observational study to investigate immune phenotypes in patients with MS following treatment with ocrelizumab. The study will be conducted on Health Sciences University Istanbul Haydarpaşa Numune Training and Research Hospital, Neurology Department. The decision to treat with ocrelizumab must be made prior to and independently from the proposal to enroll the patient into this study and in line with the Summary of Product Characteristics (SmPC) approved by the Turkish Ministry of Health. Data will be recorded at screening visit, baseline visit (month 0), second visit on 6th month, third visit on 12th month and last visit (end of the study [EOS]) on 24th month according to local clinic practice. Optional ad hoc visits could be conducted if relapse of MS or infection after vaccination occurs during ocrelizumab treatment. The duration of the study for each patient will be 24 months.

Official Title
-----------------
The Effect of Ocrelizumab on the Peripheral Lymphocyte Immunophenotypes With Suppressive Capacity in Patients With Multiple Sclerosis Previously Treated With Disease Modifying Therapy - A Prospective Exploratory Observational Study

Conditions
-----------------
Multiple Sclerosis

Intervention / Treatment
-----------------
* Drug: Ocrelizumab


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adults (≥18 years old) with a diagnosis of relapsing forms of multiple sclerosis (RMS) or primary progressive multiple sclerosis (PPMS) according to the 2017 revised McDonald criteria. Previous MS treatment with at least one of other DMT(*). The patients can be without treatment before switching until the end of wash-out period of previous DMT(s) or until lymphocytes parameter is in normal range. Previous treatment change with the reasons inefficacy, safety related issues or lack of compliance. Decision to initiate ocrelizumab therapy (in accordance with the product characteristics approved in Turkey) has already been taken for the treatment of MS patient as part of routine clinical practice. The decision to treat with Ocrelizumab must be made prior to and independently from the proposal to enroll the patient into this study. Agreed and signed informed consent. (*) A DMT is defined as any of the following drugs: Teriflunomide, Interferon beta 1a, Interferon beta 1b, Peginterferon beta 1a, Glatiramer acetate, Fingolimod, Daclizumab, Alemtuzumab, Cladribine, Dimethyl fumarate, and Natalizumab. Exclusion Criteria: Previously treated with anti-CD20 therapy (rituximab, atacicept, belimumab or ofatumumab). Medical history of a malignancy, active infection (including Hepatitis B virus) or chronic inflammatory disease. Medical history or use of any medication other than a DMT as defined above which may affect immunophenotypes of the participants.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Ocrelizumab|Ocrelizumab treatment will be administered in accordance with the product characteristics approved in Turkey.|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in T cell capacity achieved by eliminating B cells as measured by flow cytometry. | Change will be measured in absolute cell numbers and percentages from baseline to Month 6 and to Month 12. | From baseline to month 6 and month 12 | 
| Change from baseline in T cell function achieved by eliminating B cells as measured by flow cytometry. | Change will be measured in absolute cell numbers and percentages from baseline to Month 6 and to Month 12. | From baseline to month 6 and month 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation between changes in T and B cell capacity and function during course of ocrelizumab therapy. |  | Baseline (month 0), month 6 and month 12 | 
| Clinical improvement | Clinical improvement will be confirmed if an increase of less than half a step on the Expanded Disability Status Scale and less than one attack were observed during the first 12 months of ocrelizumab treatment. | Baseline (month 0), month 6 and month 12 | 
| Changes in T cells in case of relapse or infection after vaccination during ocrelizumab treatment by flow cytometry. |  | From baseline (month 0) to month 6 and month 12 | 
| Changes in B cells in case of relapse or infection after vaccination during ocrelizumab treatment by flow cytometry. |  | From baseline (month 0) to month 6 and month 12 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ocrelizumab, Disease modifying therapy, T cell, B cell