IMPACT MS
What it found
No result yet.
What was tested
Treatment tested
- Ocrelizumab
B-lymphocyte antigen CD20 binding agent
What it measured
Main measures
Comparison of intrathecal synthesis of gammaglobulins in treatment-naïve relapsing MS and clinically isolated syndrome participants before and after treatment with ocrelizumab
3 years
Who could take part
Relapsing MS · 18 to 50
Inclusion Criteria: Patients must meet the following criteria to be included in this study: * Signed Consent Form * High-risk clinically isolated syndrome or relapsing MS Diagnosis (based on 2017 International Panel Criteria) * Age 18-50 inclusive * Screening within 90 days of first clinical demyelinating event typical of MS with 1 or more inactive lesions typical of MS * No prior MS disease modifying therapy * No corticosteroids within 7 days of first ocrelizumab treatment * EDSS \< 4.0 * A negative urine or serum pregnancy test must be available for premenopausal women and for women \<12 months after the onset of menopause, unless they have undergone surgical sterilization. * Women of childbearing potential must agree to remain abstinent (refrain from heterosexual intercourse) or use one method of contraception with a failure rate of \<1% per year or a barrier method supplemented with spermicide. Contraception must continue for the duration of study treatment and for at least 24 weeks after the last dose of study treatment. A woman is considered to be of childbearing potential if she is postmenarcheal, has not reached a postmenopausal state (≥ 12 continuous months of amenorrhea with no identified cause of other than menopause), and has not undergone surgical sterilization (removal of the ovaries and/or uterus). * Examples of contraceptive methods with a failure rate of \<1% per year include bilateral tube ligation, male sterilization, established hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices. * The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence and withdrawal are not acceptable methods of contraception. * Examples of barrier methods supplemented with the use of spermicide include male or female condom, cap, diaphragm, or sponge. Exclusion Criteria: Patients will be excluded from the study based on the following criteria: * Pregnancy, lactation, or intention to become pregnant during the study * Progressive MS (primary or secondary) * Disease other than MS to explain the first demyelinating event; including AQP4 IgG seropositivity * Unwilling or unsafe to proceed with CSF exams based on coagulopathy or anatomy or other considerations in the judgment of the study investigator * Unwilling or unsafe to proceed with MRI * Active hepatitis B virus infection * Untreated latent or active tuberculosis * Active hepatitis C virus infection * HIV infection * Hypersensitivity to trial medications * History of life-threatening infusion reaction to MAbs
As registered. Criteria can change, so ask the trial team or your neurologist.
About this trial
In the sponsor's words
Newly diagnosed relapsing multiple sclerosis (MS) and high risk clinically isolated syndrome (CIS) patients will be treated with ocrelizumab at disease onset to see if treatment favorably alters CSF markers of chronic inflammation.
Papers
Background
Lassmann H, Bradl M. Multiple sclerosis: experimental models and reality. Acta Neuropathol. 2017 Feb;133(2):223-244. doi: 10.1007/s00401-016-1631-4. Epub 2016 Oct 20.Background
Bruck W, Gold R, Lund BT, Oreja-Guevara C, Prat A, Spencer CM, Steinman L, Tintore M, Vollmer TL, Weber MS, Weiner LP, Ziemssen T, Zamvil SS. Therapeutic decisions in multiple sclerosis: moving beyond efficacy. JAMA Neurol. 2013 Oct;70(10):1315-24. doi: 10.1001/jamaneurol.2013.3510.Background
Longbrake EE, Cross AH. Effect of Multiple Sclerosis Disease-Modifying Therapies on B Cells and Humoral Immunity. JAMA Neurol. 2016 Feb;73(2):219-25. doi: 10.1001/jamaneurol.2015.3977.Background
van Oosten BW, Lai M, Hodgkinson S, Barkhof F, Miller DH, Moseley IF, Thompson AJ, Rudge P, McDougall A, McLeod JG, Ader HJ, Polman CH. Treatment of multiple sclerosis with the monoclonal anti-CD4 antibody cM-T412: results of a randomized, double-blind, placebo-controlled, MR-monitored phase II trial. Neurology. 1997 Aug;49(2):351-7. doi: 10.1212/wnl.49.2.351.Background
Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H, Shen P, Moore CS, Michel L, Althekair F, Rajasekharan S, Gommerman JL, Prat A, Fillatreau S, Bar-Or A; Canadian B cells in MS Team. Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Sci Transl Med. 2015 Oct 21;7(310):310ra166. doi: 10.1126/scitranslmed.aab4176.Background
Dobson R, Ramagopalan S, Davis A, Giovannoni G. Cerebrospinal fluid oligoclonal bands in multiple sclerosis and clinically isolated syndromes: a meta-analysis of prevalence, prognosis and effect of latitude. J Neurol Neurosurg Psychiatry. 2013 Aug;84(8):909-14. doi: 10.1136/jnnp-2012-304695. Epub 2013 Feb 21.Background
Howell OW, Reeves CA, Nicholas R, Carassiti D, Radotra B, Gentleman SM, Serafini B, Aloisi F, Roncaroli F, Magliozzi R, Reynolds R. Meningeal inflammation is widespread and linked to cortical pathology in multiple sclerosis. Brain. 2011 Sep;134(Pt 9):2755-71. doi: 10.1093/brain/awr182. Epub 2011 Aug 11.Background
Magliozzi R, Howell OW, Reeves C, Roncaroli F, Nicholas R, Serafini B, Aloisi F, Reynolds R. A Gradient of neuronal loss and meningeal inflammation in multiple sclerosis. Ann Neurol. 2010 Oct;68(4):477-93. doi: 10.1002/ana.22230.Background
Stashenko P, Nadler LM, Hardy R, Schlossman SF. Characterization of a human B lymphocyte-specific antigen. J Immunol. 1980 Oct;125(4):1678-85.Background
Krumbholz M, Derfuss T, Hohlfeld R, Meinl E. B cells and antibodies in multiple sclerosis pathogenesis and therapy. Nat Rev Neurol. 2012 Nov 5;8(11):613-23. doi: 10.1038/nrneurol.2012.203. Epub 2012 Oct 9.
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History
Started
Aug 2020
Main results due
Dec 2026
Finished
Jul 2027
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