Clinical trial NCT05414487: Effects of Ofatumumab Treatment on Immune Cells and Meningeal Lymphatic Drainage in Patients With Demyelinating Diseases
Official title: Exploring the Effects of B Cell Depletion With Ofatumumab on Immune Cells and Meningeal Lymphatic Drainage in Patients With Demyelinating Diseases - a Prospective Observational Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Multiple Sclerosis
Neuromyelitis Optica Spectrum Disorder
Demyelinating Diseases of the Central Nervous System
Keywords: Multiple Sclerosis
Neuromyelitis Optica Spectrum Disorder
Demyelinating Diseases
Ofatumumab
Meningeal Lymphatic Drainage
Lead sponsor: Tianjin Medical University General Hospital
Sponsor class: OTHER
First posted: 2022-06-10
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: 1. 17 patients with relapsing remitting multiple sclerosis（RRMS）received ofatumumab treatment were enrolled.
2. 17 patients with NMOSD received ofatumumab treatment were enrolled.

Brief summary: This is an uncontrolled, prospective, observational cohort study to assess the function of meningeal lymphatic drainage and dynamics of immune cells in patients with relapsing multiple sclerosis (RMS) or Neuromyelitis optica spectrum disorder (NMOSD) after receiving ofatumumab treatment over an observational period of 12 months.

Detailed description: This is an uncontrolled, prospective, observational cohort study in patients with RMS or NMOSD who will receive ofatumumab treatment over an observational period of 12 month. Ofatumumab was administrated 20mg by subcutaneous injection on Days 1, 7 and 14 for initial loading, followed by monthly infusion up to 12 months. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) will be performed to assess meningeal lymphatic flow in participants before and after ofatumumab treatment.The change of immune cell landscape in RMS or NMOSD patients after receiving ofatumumab treatment will be monitored by mass cytometry (CyTOF). Assessments also include clinical assessments( clinical relapse rate and EDSS score) and MRI assessments (T2 lesion load, T1 gadolinium enhancing lesion number).

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent
2. RRMS subtype according to 2017 McDonald diagnostic criteria
3. Diagnosis of NMOSD according to the 2015 International Panel diagnostic criteria for NMOSD with AQP4-IgG
4. Newly diagnosed with MS/NMOSD and initiating ofatumumab treatment within the next 3 months

Exclusion Criteria:

1. Hypersensitivity to trial medications
2. History of life-threatening reaction to Ofatumumab
3. Acute or uncontrolled chronic medical condition
4. Have been treated with medications as specified or within timeframes specified (e.g. corticosteroids, rituximab, ocrelizumab, alemtuzumab, natalizumab, cyclophosphamide, claridbine, etc.)
5. Impaired hearing
6. Claustrophobia
7. 300 lbs of greater (weight limit of MRI table)
8. Pregnancy or breastfeeding
9. Sensitivity to imaging agents
10. Contraindications to MRI
11. Use of benzodiazepines, topiramate, doxycycline, mynocicline

Primary outcomes:
measure: Change from baseline in Time to Peak (TTP) of the meningeal lymphatic vessels in superior sagittal sinus (mLVs-SSS) to the end of study.
timeFrame: Baseline, Up To 12months (End of Study)
Secondary outcomes:
measure: Immune cells landscape over time
timeFrame: Baseline, month 3, month 6, month 12
measure: Adjudicated On-trial Annualized Relapse Rate (ARR)
timeFrame: Baseline, Up To 12months (End of Study)
measure: Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study
timeFrame: Baseline, Up To 12months (End of Study)
measure: Percentage of participants with new lesions by MRI assessments from baseline to the end of study
timeFrame: Baseline, Up To 12months (End of Study)
Other outcomes:
Locations:
city: Tianjin
country: China
facility: Tianjin Medical University General Hospital
state: Tianjin
Study officials:
affiliation: Department of Neurology, Tianjin Medical University General Hospital
name: Chao Zhang, M.D., Ph.D.
role: PRINCIPAL_INVESTIGATOR
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