Clinical trial NCT04874597: Investigation of the Effect of Ocrelizumab on Peripheral Lymphocyte Immunophenotypes with Suppressive Capacity in MS
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
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Multiple Sclerosis
Keywords: Ocrelizumab
Disease modifying therapy
T cell
B cell
Lead sponsor: Haydarpasa Numune Training and Research Hospital
Sponsor class: OTHER
Collaborators: name: Haydarpasa Numune Training and Research Hospital
First posted: 2021-05-05
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: A total of 20 MS patients who were previously treated with at least one of other DMT will be recruited. Participants will be recruited by specialized physicians who are experienced in the diagnosis and treatment of MS and ocrelizumab use.

* Consecutive MS patients with an already planned ocrelizumab therapy will be screened for recruitment in study recruiting clinics. Ocrelizumab treatment will not be initiated to recruit study patients.
* MS patients will be stratified for gender to reflect epidemiological incidence of MS subtypes. Gender ratios (Female/Male) for RMS and PPMS are set for 2:1 and 1:1, respectively.

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.

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.

Primary outcomes:
measure: Change from baseline in T cell capacity achieved by eliminating B cells as measured by flow cytometry.
timeFrame: From baseline to month 6 and month 12
measure: Change from baseline in T cell function achieved by eliminating B cells as measured by flow cytometry.
timeFrame: From baseline to month 6 and month 12
Secondary outcomes:
measure: Correlation between changes in T and B cell capacity and function during course of ocrelizumab therapy.
timeFrame: Baseline (month 0), month 6 and month 12
measure: Clinical improvement
timeFrame: Baseline (month 0), month 6 and month 12
measure: Changes in T cells in case of relapse or infection after vaccination during ocrelizumab treatment by flow cytometry.
timeFrame: From baseline (month 0) to month 6 and month 12
measure: Changes in B cells in case of relapse or infection after vaccination during ocrelizumab treatment by flow cytometry.
timeFrame: From baseline (month 0) to month 6 and month 12
Other outcomes:
measure: Socio-demographic data
timeFrame: Baseline (month 0)
measure: Previous MS treatment history: DMT agents and other treatments used for MS before ocrelizumab initiation
timeFrame: Screening or baseline (month 0)
measure: Previous MS treatment history: dosing, route, and treatment duration
timeFrame: Screening or baseline (month 0)
measure: Previous MS treatment history: reasons for discontinuation of each previous MS treatment
timeFrame: Screening or baseline (month 0)
measure: Medical history data
timeFrame: Baseline (month 0)
measure: Vital signs
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Vital signs
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Vital signs
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Vital signs
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Physical examination
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Physical examination
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Physical examination
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Physical examination
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: Covid-19 assessment
timeFrame: Screening, baseline (month 0), month 6, month 12 and month 24
measure: Covid-19 assessment
timeFrame: Screening, baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
measure: MS Assessment:
timeFrame: Baseline (month 0), month 6, month 12 and month 24
Locations:
city: Istanbul
country: Turkey
facility: Health Sciences University Istanbul Haydarpaşa Numune Training and Research Hospital, Neurology Department
state: Uskudar
Study officials:
References: