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- Registre américain des essais cliniques
- Essai clinique NCT07757568
Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
Type d'étude
Inscription (Réel)
Contacts et emplacements
Lieux d'étude
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Colorado
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Aurora, Colorado, États-Unis, 80045
- University of Colorado, Denver
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-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
- Adulte
- Adulte plus âgé
Accepte les volontaires sains
Méthode d'échantillonnage
Population étudiée
La description
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.)
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
Intervention / Traitement |
|---|---|
|
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.
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
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).
Délai: From baseline to 24 months
|
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
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Neurofilament light levels
Délai: From baseline to 24 Months
|
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.
|
From baseline to 24 Months
|
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Brain parenchymal volume loss (using Icometrix)
Délai: From baseline to 24 Months
|
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)
Délai: 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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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Enrique Alvarez, MD/PhD, University of Colorado, Denver
Publications et liens utiles
Publications générales
- 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.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Maladies du système nerveux
- Maladies auto-immunes
- Maladies du système immunitaire
- Maladies auto-immunes démyélinisantes, SNC
- Maladies auto-immunes du système nerveux
- Maladies démyélinisantes
- Sclérose en plaques
- Sclérose en plaques, récurrente-rémittente
- Produits chimiques organiques
- Acides, acyclique
- Acides carboxyliques
- Fumarates
- Acides dicarboxyliques
- Fumarate de diméthyle
- diroximel fumarate
Autres numéros d'identification d'étude
- 214993
Plan pour les données individuelles des participants (IPD)
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Informations sur les médicaments et les dispositifs, documents d'étude
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