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

Sponsor

Dr Recai Turkoglu (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04874597

Collaborator

Health Sciences University Istanbul Haydarpaşa Numune Training and Research Hospital (Other)

Enrollment

Location

Anticipated Duration (Months)

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis	Drug: 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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

20 participants

Observational Model:

Cohort

Time Perspective:

Prospective

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

Anticipated Study Start Date :

Oct 1, 2021

Anticipated Primary Completion Date :

May 1, 2023

Anticipated Study Completion Date :

May 1, 2024

Outcome Measures

Primary Outcome Measures

Change from baseline in T cell capacity achieved by eliminating B cells as measured by flow cytometry. [From baseline to month 6 and month 12]
Change will be measured in absolute cell numbers and percentages from baseline to Month 6 and to Month 12.
Change from baseline in T cell function achieved by eliminating B cells as measured by flow cytometry. [From baseline to month 6 and month 12]
Change will be measured in absolute cell numbers and percentages from baseline to Month 6 and to Month 12.

Secondary Outcome Measures

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 [Baseline (month 0), month 6 and month 12]
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.
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]

Other Outcome Measures

Socio-demographic data [Baseline (month 0)]
Date of birth, sex, country of birth
Previous MS treatment history: DMT agents and other treatments used for MS before ocrelizumab initiation [Screening or baseline (month 0)]
Number (%) patients receiving any DMT agents and other treatments
Previous MS treatment history: dosing, route, and treatment duration [Screening or baseline (month 0)]
Treatment duration: Date of first and last administration for first line DMT agent and other medications used for MS before ocrelizumab initiation
Previous MS treatment history: reasons for discontinuation of each previous MS treatment [Screening or baseline (month 0)]
Reasons for discontinuation includes: inefficacy/high disease activity, relapse, adverse event, lack of compliance or other.
Medical history data [Baseline (month 0)]
Medical history data includes: comorbidities, current and prior treatments for diseases other than MS, hospitalization, surgery, allergies, family history and vaccination history within the last five years.
Vital signs [Baseline (month 0), month 6, month 12 and month 24]
• Heart rate
Vital signs [Baseline (month 0), month 6, month 12 and month 24]
• Blood pressure
Vital signs [Baseline (month 0), month 6, month 12 and month 24]
• Body temperature
Vital signs [Baseline (month 0), month 6, month 12 and month 24]
• Respiratory rate
Physical examination [Baseline (month 0), month 6, month 12 and month 24]
• Height
Physical examination [Baseline (month 0), month 6, month 12 and month 24]
• Weight
Physical examination [Baseline (month 0), month 6, month 12 and month 24]
• Body mass index
Physical examination [Baseline (month 0), month 6, month 12 and month 24]
• Complete neurological and physical examination
Covid-19 assessment [Screening, baseline (month 0), month 6, month 12 and month 24]
Covid-19 polymerase chain reaction (PCR) test result (if available)
Covid-19 assessment [Screening, baseline (month 0), month 6, month 12 and month 24]
Treatment (if available)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Expanded Disability Status Scale (EDSS)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Multiple Sclerosis Functional Composite (MSFC)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Symbol Digit Modalities Test (SDMT)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Nine-Hole Peg Test (9-HPT)
MS Assessment: [Baseline (month 0), month 6, month 12 and month 24]
• Timed 25-foot walk test (25-FWT)

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.