Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)
研究概览
详细说明
研究类型
注册 (实际的)
联系人和位置
学习地点
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Colorado
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Aurora、Colorado、美国、80045
- University of Colorado, Denver
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参与标准
资格标准
适合学习的年龄
- 成人
- 年长者
接受健康志愿者
取样方法
研究人群
描述
Inclusion Criteria:
- Diagnosed with relapsing forms of MS
- > 18 years of age at the time of initiation of de-escalation
- No evidence of new inflammatory disease activity (no new T2/contrast enhancing lesions, absence of relapses) for at least two years prior to de-escalation
- Have had multiple sclerosis related symptoms at least 3 years prior to baseline visit.
- Taking an anti-CD20 therapy most recently as a DMT continuously for at least one year (have received at least 2 courses) prior to de-escalation.
- Are 6-12 months from their last anti-CD20 infusion
- Willing to follow the protocol
- Able to undergo a brain MRI without anesthesia
Exclusion Criteria:
- Any progression of neurological symptoms in the year prior to the screening visit that would be consistent with progressive MS.
- Use of any non-FDA-approved DMT or systemic corticosteroids in the last 2 years. (Note: Use of inhaled or topical steroids are not an exclusion criteria. Also, use of oral steroids for no greater than 14 days given for a non-MS condition is not exclusionary).
- IgG levels <300 mg/dL
- lymphocytes <800 cells/mm3
- EDSS >6.5
- Is considering pregnancy at the screening visit
- Prior use of alemtuzumab, mitoxantrone, cyclophosphamide, methotrexate, cyclosporine or any experimental MS treatment in the last 5 years.
- Prior allergy to Vumerity
- Other significant medical or psychiatric illness, if uncontrolled. Examples: uncontrolled hypertension, uncontrolled diabetes, uncontrolled asthma, uncontrolled depression
- Cancers other than basal cell skin cancers within the last 5 years
- Unable to give informed consent or follow the protocol.
- Unable to undergo brain MRI.
- History of other chronic neurological illnesses that might mimic MS with chronic or intermittent symptoms (i.e. ALS, myasthenia gravis, chronic neuropathy, etc.)
学习计划
研究是如何设计的?
设计细节
队列和干预
团体/队列 |
干预/治疗 |
|---|---|
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De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)
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Titration starting with 231 mg twice a day, orally, for 7 days (per United States Product information).
Then continue with 462 mg orally (administered as two 231 mg capsules) twice a day.
Titration will start with 120mg twice a day, orally, for 7 days (per United States product information) and then continue with 240mg twice a day orally.
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Components of No Evidence of Disease Activity (NEDA-3) components (of which are no relapse activity, no MRI disease activity and no confirmed disability progression).
大体时间:From baseline to 24 months
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Number of subjects not meeting NEDA defined as:
The time with NEDA (primary outcome) will be described using product-limit estimates (Kaplan-Meier plots). With 20 patients, if there is no evidence of disease activity in any patients in 24 months, we are 90% confident that the true rate is below 17%. Similarly with 1, 2, and 3 patients with observable disease activity in 24 months, the true rates are between 0.1-25%, 1-32% and 3-38% respectively. |
From baseline to 24 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Neurofilament light levels
大体时间:From baseline to 24 Months
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Neurofilament light levels: Neurofilament light chain is a biomarker of neuroaxonal injury measured in serum or plasma.
Unit: pg/mL (picograms per milliliter).
Range: Continuous, with higher values indicating greater neuroaxonal damage.
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From baseline to 24 Months
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Brain parenchymal volume loss (using Icometrix)
大体时间:From baseline to 24 Months
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Brain parenchymal volume loss (using iCOMETRIX): Volume is quantified from serial MRI scans using the FDA-cleared iCOMETRIX (icobrain) software platform.
Unit: Percentage change in brain parenchymal volume from baseline.
Range: Continuous Negative values indicate brain volume loss; larger negative percentages reflect greater tissue loss.
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From baseline to 24 Months
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Multiple Sclerosis Functional Composite (MSFC)
大体时间:From baseline to 24 Months
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Assessment of MS-related disability that evaluates ambulation (Timed 25-Foot Walk), upper extremity function (9-Hole Peg Test), and cognitive processing speed.
Continuous composite score calculated as the mean of standardized z-scores from the three component tests.
Positive scores indicate better function and negative scores indicate worse function.
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From baseline to 24 Months
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合作者和调查者
调查人员
- 首席研究员:Enrique Alvarez, MD/PhD、University of Colorado, Denver
出版物和有用的链接
一般刊物
- Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.
- Wallin MT, Culpepper WJ, Campbell JD, Nelson LM, Langer-Gould A, Marrie RA, Cutter GR, Kaye WE, Wagner L, Tremlett H, Buka SL, Dilokthornsakul P, Topol B, Chen LH, LaRocca NG; US Multiple Sclerosis Prevalence Workgroup. The prevalence of MS in the United States: A population-based estimate using health claims data. Neurology. 2019 Mar 5;92(10):e1029-e1040. doi: 10.1212/WNL.0000000000007035. Epub 2019 Feb 15.
- Cohan SL, Edwards K, Lucas L, Gervasi-Follmar T, O'Connor J, Siuta J, Kamath V, Garten L, Chen C, Thomas J, Smoot K, Kresa-Reahl K, Spinelli KJ. Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy. Mult Scler J Exp Transl Clin. 2019 Jan 16;5(1):2055217318824618. doi: 10.1177/2055217318824618. eCollection 2019 Jan-Mar.
- Cohan SL, Moses H, Calkwood J, Tornatore C, LaGanke C, Smoot KE, Meka V, Okwuokenye M, Hotermans C, Mendoza JP, Mann MK, Meltzer LA. Clinical outcomes in patients with relapsing-remitting multiple sclerosis who switch from natalizumab to delayed-release dimethyl fumarate: A multicenter retrospective observational study (STRATEGY). Mult Scler Relat Disord. 2018 May;22:27-34. doi: 10.1016/j.msard.2018.02.028. Epub 2018 Feb 26.
- Kalincik T, Vivek V, Jokubaitis V, Lechner-Scott J, Trojano M, Izquierdo G, Lugaresi A, Grand'maison F, Hupperts R, Oreja-Guevara C, Bergamaschi R, Iuliano G, Alroughani R, Van Pesch V, Amato MP, Slee M, Verheul F, Fernandez-Bolanos R, Fiol M, Spitaleri DL, Cristiano E, Gray O, Cabrera-Gomez JA, Shaygannejad V, Herbert J, Vucic S, Needham M, Petkovska-Boskova T, Sirbu CA, Duquette P, Girard M, Grammond P, Boz C, Giuliani G, Rio ME, Barnett M, Flechter S, Moore F, Singhal B, Bacile EA, Saladino ML, Shaw C, Skromne E, Poehlau D, Vella N, Spelman T, Liew D, Kilpatrick TJ, Butzkueven H; MSBase Study Group. Sex as a determinant of relapse incidence and progressive course of multiple sclerosis. Brain. 2013 Dec;136(Pt 12):3609-17. doi: 10.1093/brain/awt281. Epub 2013 Oct 18.
- Inusah S, Sormani MP, Cofield SS, Aban IB, Musani SK, Srinivasasainagendra V, Cutter GR. Assessing changes in relapse rates in multiple sclerosis. Mult Scler. 2010 Dec;16(12):1414-21. doi: 10.1177/1352458510379246. Epub 2010 Sep 1.
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 214993
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
药物和器械信息、研究文件
研究美国 FDA 监管的药品
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