Multiple Sclerosis (MS) Relapsing RemittingNCT07757568
Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)
An observational study of Multiple Sclerosis (MS) Relapsing Remitting, run by University of Colorado, Denver at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis (MS) Relapsing Remitting
- What is being tested?
- Vumerity and Tecfidera
- Type of treatment
- Pill or oral medicine
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Mar 2023to 7 Nov 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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.)
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Colorado, Denver
Aurora, Colorado, 80045
About this study
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.
Read the detailed description
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.
- Being tested
- Vumerity, Tecfidera
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VumerityDrug
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.
TecfideraDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) | Not described Receives: Drug: Vumerity; Drug: Tecfidera |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- Evidence of Relapse activity - collected via monthly phone calls and study visits. OR
- MRI disease activity - presence of new lesions (T2 or Gd enhancing) on scans done at baseline, months 12 and 24. OR
- 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.
Measured: From baseline to 24 months
Secondary outcomes (3)
Neurofilament light levels
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.
Measured: From baseline to 24 Months
Brain parenchymal volume loss (using Icometrix)
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.
Measured: From baseline to 24 Months
Multiple Sclerosis Functional Composite (MSFC)
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.
Measured: From baseline to 24 Months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Aug 2026
- Study start7 Mar 2023
- Primary completion1 Sep 2026 (estimated)
- Study completion7 Nov 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Multiple Sclerosis (MS) Relapsing RemittingStudies of the same condition, open and under way.
- More trials run by University of Colorado, DenverThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Other
- Time perspective
- Prospective
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Colorado, Denver
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Enrique Alvarez, MD/PhD, Principal investigator, University of Colorado, Denver
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07757568
- Sponsor's protocol ID
- 214993
- Status last verified
- Aug 2026
- First submitted
- 12 Sep 2025
- Last updated
- 11 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- Individual data sharing
- Undecided
Publications
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.
PubMed 18272891Cohan 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.
PubMed 30729028Cohan 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.
PubMed 29524759Kalincik 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.
PubMed 24142147Inusah 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.
PubMed 20810517Wallin 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.
PubMed 30770430
Study at a glance
From the registry record, last updated by the sponsor on 11 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of De-Escalation From antiCD-20 Therapies to Dimethyl Fumarate (Tecfidera) or Diroximel Fumarate (Vumerity)
- ClinicalTrials.gov ID
- NCT07757568
- Acronym / sponsor ID
- 214993
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 11 participants (actual)
- Lead sponsor
- University of Colorado, DenverUniversity, hospital or other
- Study start
- 7 Mar 2023 (actual)
- Primary completion
- 1 Sep 2026 (estimated)
- Study completion
- 7 Nov 2026 (estimated)
- First posted
- 11 Aug 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Other
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) | – | Drug: Vumerity, Drug: Tecfidera |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| VumerityTitration 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. | Drug | De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) |
| TecfideraTitration 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. | Drug | De-escalation therapy to diroximmel fumarate (Vumerity®) or dimethyl fumarate (Tecfidera®) |
Primary outcome
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).
Time frame: 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.
3 secondary outcomes
Neurofilament light levels
Time frame: From baseline to 24 Months
Brain parenchymal volume loss (using Icometrix)
Time frame: From baseline to 24 Months
Multiple Sclerosis Functional Composite (MSFC)
Time frame: From baseline to 24 Months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Aug 2026.
- Background: PubMed 18272891Hauser 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.
- Background: PubMed 30729028Cohan 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.
- Background: PubMed 29524759Cohan 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.
- Background: PubMed 24142147Kalincik 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.
- Background: PubMed 20810517Inusah 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.
- Background: PubMed 30770430Wallin 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Enrique Alvarez, MD/PhD principal investigator
University of Colorado, Denver
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Multiple Sclerosis (MS) Relapsing Remitting, run by University of Colorado, Denver at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). (time frame: From baseline to 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07757568, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.