Clinical trial NCT04478591: The Wearing-off Phenomenon of Ocrelizumab in Patients With Multiple Sclerosis
Official title: The Wearing-off Phenomenon of Ocrelizumab in Patients With Multiple Sclerosis
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Ocrelizumab
Wearing-off effect
Neurofilament Light
Extended dosing
Lead sponsor: Amsterdam UMC, location VUmc
Sponsor class: OTHER
First posted: 2020-07-20
Enrollment: 117
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with multiple sclerosis using ocrelizumab.

Brief summary: The primary goal of this research is to study the prevalence of the wearing-off effect and possible risk factors for wearing-off symptoms in patients with multiple sclerosis using ocrelizumab with the use of questionnaires. Furthermore, the goal is to study whether patients receiving extended dosing of ocrelizumab experience more wearing-off symptoms or adverse events in general. Finally, we would like to extend knowledge on wearing-off symptoms in general.

Detailed description: Ocrelizumab is a monoclonal antibody very effective for the treatment of relapsing-remitting multiple sclerosis and primary progressive multiple sclerosis. Ocrelizumab is usually administered intravenous every six months. Natalizumab is another type of treatment used for relapsing-remitting multiple sclerosis and is administered every four weeks. Often patients report MS-related symptoms just prior to their next infusion such as fatigue, coordination problems or motor problems, the so-called wearing-off phenomenon. The exact etiology of this phenomenon remains unknown. Although not studied before, patients do report similar symptoms when using ocrelizumab. Furthermore, because of the COVID-19 pandemic, some patients receive extended dosing of ocrelizumab based on b-cell count. Whether this can increase wearing-off symptoms is unknown.

The goal of this research is to study the prevalence of wearing-off symptoms and possible risk factors for wearing-off symptoms in patients with multiple sclerosis using ocrelizumab. All patients using ocrelizumab during one year or more that provided written informed consent to participate in the study will be asked to complete three questionnaires before or during their next treatment with ocrelizumab. The questionnaires that will be used are the MSIS-29, the treatment satisfaction questionnaire and a questionnaire about wearing-off symptoms. Exact weight of the participants will be measured. Information about age, gender, date of diagnosis, start date of ocrelizumab, clinical and radiological disease activity, EDSS score, b-cell count and the biomarker neurofilament light will be extracted from the patient files. After two weeks, participants receive two additional digital questionnaires, the MSIS-29 and a follow-up questionnaire about wearing-off symptoms.

Eligibility criteria: Inclusion Criteria:

* 18 years or older
* Diagnosis multiple sclerosis
* Use of ocrelizumab as a treatment for multiple sclerosis for a minimum of one year

Exclusion Criteria:

* Unable to answer questionnaires in Dutch
* Different infusion protocol during the previous ocrelizumab infusion (e.g. 300 mg of ocrelizumab instead of 600 mg).

Primary outcomes:
measure: Wearing-off symptoms
timeFrame: Baseline
Secondary outcomes:
measure: % of wearing-off symptoms (yes/no assessed on questionnaires) in correlation to the % of patients with extended dosing versus standard dosing with ocrelizumab.
timeFrame: At baseline (prior to next infusion with ocrelizumab)
measure: Neurofilament light levels in patients with wearing-off symptoms.
timeFrame: At baseline (prior to next infusion with ocrelizumab)
measure: Absolute B-cells count in blood in correlation to the presence of wearing-off symptoms (yes/no assessed on questionnaires)
timeFrame: At baseline (prior to next infusion with ocrelizumab)
measure: Type of multiple sclerosis (either RRMS or PPMS) in correlation to % of patients with wearing-off symptoms (yes/no assessed on questionnaires).
timeFrame: At baseline (prior to next infusion with ocrelizumab)
measure: Treatment satisfaction score measured by the treatment satisfaction questionnaire in correlation to the % of patients with wearing-off symptoms (yes/no assessed on questionnaires)
timeFrame: At baseline (prior to next infusion with ocrelizumab)
measure: Self-reported disability (MSIS-29 questionnaire) compared before and after ocrelizumab infusion in patients with wearing-off symptoms
timeFrame: At baseline (prior to next infusion with ocrelizumab) and after two weeks
measure: Self-reported disability (MSIS-29 questionnaire) after ocrelizumab infusion in patients without wearing-off symptoms
timeFrame: At baseline (prior to next infusion with ocrelizumab) and after two weeks
measure: Change of wearing-off symptoms after ocrelizumab infusion in patients with wearing-off symptoms
timeFrame: Two weeks after ocrelizumab infusion
measure: Post-dose symptoms after ocrelizumab infusion
timeFrame: Two weeks after ocrelizumab infusion
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Amsterdam UMC, location VUmc
state: North-Holland
Study officials:
affiliation: Amsterdam UMC, location VUmc
name: Joep Killestein, MD, PhD.
role: PRINCIPAL_INVESTIGATOR
References: