Effects of Ofatumumab Treatment on Immune Cells and Meningeal Lymphatic Drainage in Patients With Demyelinating Diseases

Recruiting

• Conditions: Neuromyelitis Optica Spectrum Disorder; Demyelinating Diseases of the Central Nervous System; Multiple Sclerosis
• Interventions: Drug: Ofatumumab

• Registration Number: NCT05414487
• Lead Sponsor: Tianjin Medical University General Hospital

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).

Study Timeline

• Study First Submitted: 2022-06-06
• Study First Submitted QC: 2022-06-09
• Study First Posted: 2022-06-10
• Status Verified: 2022-10
• Study Start: 2022-10-15
• Last Update Submitted: 2022-10-19
• Last Update Posted: 2022-10-20
• Primary Completion: 2023-12-01
• Study Completion: 2024-06-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 34

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Ofatumumab	Ofatumumab	17 RMS patients and 17 NMOSD patients prescribed with Ofatumumab will be enrolled after informed consent.

Primary Outcome Measures

Name	Time	Method
Change from baseline in Time to Peak (TTP) of the meningeal lymphatic vessels in superior sagittal sinus (mLVs-SSS) to the end of study.	Baseline, Up To 12months (End of Study)	The image of mLVs-SSS in participants will be detected by Dynamic contrast-enhanced MRI (DCE-MRI) before and after ofatumumab treatment.MRI images would be analyzed by three radiologists independently, and each of them is blinded to the patients' information. The obtained DCE-MRI data are interpreted semi-quantitatively to generate TTP.

Secondary Outcome Measures

Name	Time	Method
Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the end of study	Baseline, Up To 12months (End of Study)	Disease-related disability was measured by the EDSS before and after ofatumumab treatment. The EDSS was an ordinal clinical rating scale that ranges from 0 (normal neurologic examination) to 10 (death) in half-point increments.
Immune cells landscape over time	Baseline, month 3, month 6, month 12	The dynamics of immune cells in participants will be detected by mass cytometry (CyTOF) before and after ofatumumab treatment.
Adjudicated On-trial Annualized Relapse Rate (ARR)	Baseline, Up To 12months (End of Study)	The adjudicated On-trial ARR was computed as the total number of relapses divided by the total number of patient years in the study period. A central independent committee was used to adjudicate all On-trial Relapses as determined by the treating physician. Results reported as adjusted adjudicated On-trial ARR based on a Poisson regression adjusted for randomization strata and historical ARR in 24 months prior to Screening.
Percentage of participants with new lesions by MRI assessments from baseline to the end of study	Baseline, Up To 12months (End of Study)	Magnetic Resonance Imaging (MRI) will be used to measure presence of increase in number of gadolinium enhancing lesions and T2 lesion load. Each MRI scan will be previewed by a local neuroradiologist. The quality of each scan performed will be assessed by a central MRI reading center and evaluated for quality, completeness and adherence to the protocol.

Trial Locations

Locations (1)

Tianjin Medical University General Hospital; 🇨🇳 Tianjin, Tianjin, China