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Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)

6. august 2026 opdateret af: University of Colorado, Denver
The investigators propose a multi-center pilot study, which aims to evaluate safety and efficacy of fumarates as de-escalation therapy in clinically stable MS patients previously treated with anti-CD20 therapy.

Studieoversigt

Status

Aktiv, ikke rekrutterende

Detaljeret beskrivelse

Ten patients >18 years of age with a minimum of 2 years of MS disease stability (no relapse or new magnetic resonance imaging lesions) and at least one year of experience on an anti-CD20 agent prior to initiating de-escalation with diroximel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) will be followed for 24 months post de-escalation. To account for screen failures and withdrawals, up to 15 may be enrolled.

Undersøgelsestype

Observationel

Tilmelding (Faktiske)

11

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiesteder

    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • University of Colorado, Denver

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

  • Voksen
  • Ældre voksen

Tager imod sunde frivillige

Ingen

Prøveudtagningsmetode

Ikke-sandsynlighedsprøve

Studiebefolkning

Patients between the ages of >18 with a minimum of 2 years of MS disease stability and at least one year of experience on an anti-CD20 agent prior to initiating de-escalation with Vumerity will be followed for 24 months post de-escalation.

Beskrivelse

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.)

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

Kohorter og interventioner

Gruppe / kohorte
Intervention / Behandling
De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)
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.

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
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).
Tidsramme: From baseline to 24 months

Number of subjects not meeting NEDA defined as:

  1. Evidence of Relapse activity - collected via monthly phone calls and study visits.

    OR

  2. MRI disease activity - presence of new lesions (T2 or Gd enhancing) on scans done at baseline, months 12 and 24.

    OR

  3. 6 months Confirmed Disability progression (CDP6): measured by EDSS done at baseline and every 6 months. CDP6 is defined as an increase in EDSS score of ≥1.5 if baseline EDSS was 0; or ≥1.0 points if baseline EDSS was ≥0.5-≤5; or by ≥0.5 points if baseline EDSS ≥6, sustained over two consecutive visits for ≥6 months.

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

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Neurofilament light levels
Tidsramme: 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
Brain parenchymal volume loss (using Icometrix)
Tidsramme: 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.
From baseline to 24 Months
Multiple Sclerosis Functional Composite (MSFC)
Tidsramme: From baseline to 24 Months
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.
From baseline to 24 Months

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Efterforskere

  • Ledende efterforsker: Enrique Alvarez, MD/PhD, University of Colorado, Denver

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Generelle publikationer

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

7. marts 2023

Primær færdiggørelse (Anslået)

1. september 2026

Studieafslutning (Anslået)

7. november 2026

Datoer for studieregistrering

Først indsendt

12. september 2025

Først indsendt, der opfyldte QC-kriterier

6. august 2026

Først opslået (Faktiske)

11. august 2026

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

11. august 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

6. august 2026

Sidst verificeret

1. august 2026

Mere information

Begreber relateret til denne undersøgelse

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