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

NCT07757568 | Active Not Recruiting DMC FDA Drug

• 1 other identifier: 214993
• Study Type: observational
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Multiple Sclerosis (MS) Relapsing Remitting

Outcome Measures

Primary Outcomes (1)

• 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).

  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

Secondary Outcomes (3)

• Neurofilament light levels

  From baseline to 24 Months

• Brain parenchymal volume loss (using Icometrix)

  From baseline to 24 Months

• Multiple Sclerosis Functional Composite (MSFC)

  From baseline to 24 Months

Study Arms (1)

De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)

Drug: Vumerity; Drug: Tecfidera

Interventions

Vumerity DRUG

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.

De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)

Tecfidera DRUG

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.

De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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

You may not qualify if:

• Any progression of neurological symptoms in the year prior to the screening visit that would be consistent with progressive MS.
• 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.)

Sponsors & Collaborators

• University of Colorado, Denver: lead

Study Sites (1)

University of Colorado, Denver

Aurora, Colorado, 80045, United States

Location

Related Publications (6)

• 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.

  PMID: 18272891 BACKGROUND

• 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.

  PMID: 30729028 BACKGROUND

• 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.

  PMID: 29524759 BACKGROUND

• 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.

  PMID: 24142147 BACKGROUND

• 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.

  PMID: 20810517 BACKGROUND

• 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.

  PMID: 30770430 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Biorepository: If subjects from either site consent, left over samples from this study will be collected and stored in a HIPAA compliant database, owned by the Rocky Mountain MS Center Biorepository (University of Colorado COMIRB 12-0968). All identifiable information collected in this study will be protected. If the patient wants to have their left-over sample destroyed, they can contact the Rocky Mountain MS Center Biorepository

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting

Interventions

diroximel fumarate; Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Enrique Alvarez, MD/PhD

  University of Colorado, Denver

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2025
• First Posted: August 11, 2026
• Study Start: March 7, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): November 7, 2026
• Last Updated: August 11, 2026

Record last verified: 2026-08

Locations

US (1)