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

NCT05414487 | Unknown FDA Drug

• 1 other identifier: COMB157GCN02T
• Study Type: observational
• Target: 34
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• Change from baseline in Time to Peak (TTP) of the meningeal lymphatic vessels in superior sagittal sinus (mLVs-SSS) to the 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.

  Baseline, Up To 12months (End of Study)

Secondary Outcomes (4)

• Immune cells landscape over time

  Baseline, month 3, month 6, month 12

• Adjudicated On-trial Annualized Relapse Rate (ARR)

  Baseline, Up To 12months (End of Study)

• 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)

• Percentage of participants with new lesions by MRI assessments from baseline to the end of study

  Baseline, Up To 12months (End of Study)

Study Arms (1)

Ofatumumab

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

Drug: Ofatumumab

Interventions

Ofatumumab DRUG

There is no treatment allocation. Patients with MS or NMOSD administered Ofatumumab by prescription will be enrolled. Participants will receive 20mg ofatumumab (20 mg/0.4 ml) by subcutaneous injection. Ofatumumab is administrated at baseline, Day 7, Day 14 and monthly thereafter until the end of the study.

Ofatumumab

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Tianjin Medical University General Hospital: lead

Study Sites (1)

Tianjin Medical University General Hospital

Tianjin, Tianjin Municipality, 300052, China

RECRUITING

Related Publications (11)

• Bar-Or A, Li R. Cellular immunology of relapsing multiple sclerosis: interactions, checks, and balances. Lancet Neurol. 2021 Jun;20(6):470-483. doi: 10.1016/S1474-4422(21)00063-6. Epub 2021 Apr 27.

  PMID: 33930317 BACKGROUND

• Couloume L, Ferrant J, Le Gallou S, Mandon M, Jean R, Bescher N, Zephir H, Edan G, Thouvenot E, Ruet A, Debouverie M, Tarte K, Ame P, Roussel M, Michel L. Mass Cytometry Identifies Expansion of T-bet+ B Cells and CD206+ Monocytes in Early Multiple Sclerosis. Front Immunol. 2021 May 4;12:653577. doi: 10.3389/fimmu.2021.653577. eCollection 2021.

  PMID: 34017332 BACKGROUND

• Hershenhouse KS, Shauly O, Gould DJ, Patel KM. Meningeal Lymphatics: A Review and Future Directions From a Clinical Perspective. Neurosci Insights. 2019 Dec 31;14:1179069519889027. doi: 10.1177/1179069519889027. eCollection 2019.

  PMID: 32363346 BACKGROUND

• Migotto MA, Mardon K, Orian J, Weckbecker G, Kneuer R, Bhalla R, Reutens DC. Efficient Distribution of a Novel Zirconium-89 Labeled Anti-cd20 Antibody Following Subcutaneous and Intravenous Administration in Control and Experimental Autoimmune Encephalomyelitis-Variant Mice. Front Immunol. 2019 Oct 18;10:2437. doi: 10.3389/fimmu.2019.02437. eCollection 2019.

  PMID: 31681317 BACKGROUND

• Louveau A, Herz J, Alme MN, Salvador AF, Dong MQ, Viar KE, Herod SG, Knopp J, Setliff JC, Lupi AL, Da Mesquita S, Frost EL, Gaultier A, Harris TH, Cao R, Hu S, Lukens JR, Smirnov I, Overall CC, Oliver G, Kipnis J. CNS lymphatic drainage and neuroinflammation are regulated by meningeal lymphatic vasculature. Nat Neurosci. 2018 Oct;21(10):1380-1391. doi: 10.1038/s41593-018-0227-9. Epub 2018 Sep 17.

  PMID: 30224810 BACKGROUND

• Wang X, Tian H, Liu H, Liang D, Qin C, Zhu Q, Meng L, Fu Y, Xu S, Zhai Y, Ding X, Wang X. Impaired Meningeal Lymphatic Flow in NMOSD Patients With Acute Attack. Front Immunol. 2021 Jun 14;12:692051. doi: 10.3389/fimmu.2021.692051. eCollection 2021.

  PMID: 34194440 BACKGROUND

• Zhang C, Zhang TX, Liu Y, Jia D, Zeng P, Du C, Yuan M, Liu Q, Wang Y, Shi FD. B-Cell Compartmental Features and Molecular Basis for Therapy in Autoimmune Disease. Neurol Neuroimmunol Neuroinflamm. 2021 Aug 31;8(6):e1070. doi: 10.1212/NXI.0000000000001070. Print 2021 Nov.

  PMID: 34465614 BACKGROUND

• Leipold MD, Maecker HT. Mass cytometry: protocol for daily tuning and running cell samples on a CyTOF mass cytometer. J Vis Exp. 2012 Nov 2;(69):e4398. doi: 10.3791/4398.

  PMID: 23149654 BACKGROUND

• Thrash EM, Kleinsteuber K, Hathaway ES, Nazzaro M, Haas E, Hodi FS, Severgnini M. High-Throughput Mass Cytometry Staining for Immunophenotyping Clinical Samples. STAR Protoc. 2020 Jun 30;1(2):100055. doi: 10.1016/j.xpro.2020.100055. eCollection 2020 Sep 18.

  PMID: 33111099 BACKGROUND

• Ding XB, Wang XX, Xia DH, Liu H, Tian HY, Fu Y, Chen YK, Qin C, Wang JQ, Xiang Z, Zhang ZX, Cao QC, Wang W, Li JY, Wu E, Tang BS, Ma MM, Teng JF, Wang XJ. Impaired meningeal lymphatic drainage in patients with idiopathic Parkinson's disease. Nat Med. 2021 Mar;27(3):411-418. doi: 10.1038/s41591-020-01198-1. Epub 2021 Jan 18.

  PMID: 33462448 BACKGROUND

• Yang S, Zhang TX, Liu J, Liu Z, Zhu L, Li YY, Feng B, Fan M, Shi FD, Zhang C. Reconstitution of CXCR3+ CCR6+ Th17.1-Like T Cells in Response to Ofatumumab Therapy in Patients With Multiple Sclerosis. Ann Clin Transl Neurol. 2025 May;12(5):1043-1053. doi: 10.1002/acn3.70042. Epub 2025 Mar 31.

  PMID: 40164501 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

Peripheral Blood of participants

MeSH Terms

Conditions

Multiple Sclerosis; Neuromyelitis Optica; Demyelinating Diseases

Interventions

ofatumumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Autoimmune Diseases; Immune System Diseases; Myelitis, Transverse; Optic Neuritis; Optic Nerve Diseases; Cranial Nerve Diseases; Eye Diseases

Study Officials

• Chao Zhang, M.D., Ph.D.

  Department of Neurology, Tianjin Medical University General Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Chao Zhang, M.D., Ph.D.

CONTACT

+8602260814587; chaozhang@tmu.edu.cn

Shu Yang, M.D., Ph.D.

CONTACT

+8615922023036; yangshu_0413@163.com

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: June 6, 2022
• First Posted: June 10, 2022
• Study Start: October 15, 2022
• Primary Completion: December 1, 2023
• Study Completion: June 1, 2024
• Last Updated: October 20, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)