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

• Sponsor: Tianjin Medical University General Hospital (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT05414487
• Collaborator: (none)
• Enrollment: 34
• Location: 1
• Anticipated Duration (Months): 23.6
• Patients Per Site Per Month: 1.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorder; Demyelinating Diseases of the Central Nervous System	Drug: Ofatumumab

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 Design

• Study Type: Observational
• Anticipated Enrollment: 34 participants
• Observational Model: Cohort
• Time Perspective: Prospective
• 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
• Anticipated Study Start Date: Jun 15, 2022
• Anticipated Primary Completion Date: Dec 1, 2023
• Anticipated Study Completion Date: Jun 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Ofatumumab 17 RMS patients and 17 NMOSD patients prescribed with Ofatumumab will be enrolled after informed consent.	Drug: Ofatumumab; 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.

Outcome Measures

Primary Outcome Measures

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. [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

1. 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.

2. 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.

3. 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.

4. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Tianjin Medical University General Hospital	Tianjin	Tianjin	China	300052

Sponsors and Collaborators

• Tianjin Medical University General Hospital

Investigators

• Principal Investigator: Chao Zhang, M.D., Ph.D., Department of Neurology, Tianjin Medical University General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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. Review.
• 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, Amé 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.
• 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.
• 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. Review.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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). pii: e1070. doi: 10.1212/NXI.0000000000001070. Print 2021 Nov.

• Responsible Party: Chao Zhang, Professor, Tianjin Medical University General Hospital
• ClinicalTrials.gov Identifier: NCT05414487
• Other Study ID Numbers: COMB157GCN02T
• First Posted: Jun 10, 2022
• Last Update Posted: Jun 21, 2022
• Last Verified: Jun 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Chao Zhang, Professor, Tianjin Medical University General Hospital: Multiple Sclerosis; Neuromyelitis Optica Spectrum Disorder; Demyelinating Diseases; Ofatumumab; Meningeal Lymphatic Drainage
• Additional relevant MeSH terms: Multiple Sclerosis; Neuromyelitis Optica; Demyelinating Diseases; Sclerosis; Ofatumumab

Study Results

No Results Posted as of Jun 21, 2022