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

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

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

Study Overview

• Status: Active, not recruiting
• Conditions: Multiple Sclerosis
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Actual): 30

Contacts and Locations

• Study Contact: Name: Recai Türkoğlu, MD, Prof.; Phone Number: +90 (216) 542 32 32; Email: recaiturkoglu@hotmail.com

Study Locations

• Turkey
  • Uskudar
    • Istanbul, Uskudar, Turkey, 34668
      • Health Sciences University Istanbul Haydarpaşa Numune Training and Research Hospital, Neurology Department
      • Contact: Recai Türkoğlu, MD, Prof.; Phone Number: +90 (216) 542 32 32; Email: recaiturkoglu@hotmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• 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.

Description

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.

Study Plan

How is the study designed?

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

Other Outcome Measures

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

Collaborators and Investigators

• Sponsor: Dr Recai Turkoglu
• Collaborators: Health Sciences University Istanbul Haydarpaşa Numune Training and Research Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): November 1, 2023
• Study Completion (Anticipated): November 1, 2023

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: May 4, 2021
• First Posted (Actual): May 5, 2021

Study Record Updates

• Last Update Posted (Actual): May 1, 2023
• Last Update Submitted That Met QC Criteria: April 28, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: T cell; Ocrelizumab; B cell; Disease modifying therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Ocrelizumab
• Other Study ID Numbers: ML42254

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No