Multiple Sclerosis Clinical Trial
— OMNISCIENCEOfficial 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
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.
Status | Recruiting |
Enrollment | 34 |
Est. completion date | June 1, 2024 |
Est. primary completion date | December 1, 2023 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years to 80 Years |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
China | Tianjin Medical University General Hospital | Tianjin | Tianjin |
Lead Sponsor | Collaborator |
---|---|
Tianjin Medical University General Hospital |
China,
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
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. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | 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 | Immune cells landscape over time | The dynamics of immune cells in participants will be detected by mass cytometry (CyTOF) before and after ofatumumab treatment. | Baseline, month 3, month 6, month 12 | |
Secondary | Adjudicated On-trial Annualized Relapse Rate (ARR) | 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. | Baseline, Up To 12months (End of Study) | |
Secondary | Percentage of Participants With Worsening in Expanded Disability Severity Scale (EDSS) Score From Baseline to the 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. | Baseline, Up To 12months (End of Study) | |
Secondary | Percentage of participants with new lesions by MRI assessments from baseline to the 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. | Baseline, Up To 12months (End of Study) |
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