Evidence map›Paper›PMID 38662979›Full record

Trial reportNeurology(R) neuroimmunology & neuroinflammation2024

Safety and Dose-Response of Vidofludimus Calcium in Relapsing Multiple Sclerosis: Extended Results of a Placebo-Controlled Phase 2 Trial.

Robert J Fox, Heinz Wiendl, Christian Wolf, Nicola De Stefano, Johann Sellner, Viktoriia Gryb, Konrad Rejdak, Plamen S Bozhinov, Daniel Vitt, Hella Kohlhof and 5 more

Registry-linked trialOpen access · goldAbstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology(R) neuroimmunology & neuroinflammation, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03846219 (Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial Assessing the Effect of IMU-838 on Disease Activity, as Measured by Magnetic Resonance Imaging), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT03846219 phase2active not recruitingnot on this map

Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial Assessing the Effect of IMU-838 on Disease Activity, as Measured by Magnetic Resonance Imaging (MRI), as Well as Safety and Tolerability in Patients With Relapsing-remitting Multiple Sclerosis (RRMS)

TypeinterventionalSponsorImmunic AGRan2019 to 2029Enrolled210ConditionsRelapsing-Remitting Multiple Sclerosis (RRMS)ArmsIMU-838 (30 mg/day), IMU-838 (45 mg/day), Placebo, IMU-838 (10 mg/day)
3 · Its place in the literature

Who cites it

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Progressive multiple sclerosis: Evaluating current therapies and exploring future treatment strategies.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  5. Review
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

15 authors at 1 institution in 1 country.

Robert J FoxFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.ORCID 0000-0002-4263-3717
Heinz WiendlFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.ORCID 0000-0003-4310-3432
Christian WolfFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.ORCID 0000-0002-4683-0507
Nicola De StefanoFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.ORCID 0000-0003-4930-7639
Johann SellnerFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Viktoriia GrybFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Konrad RejdakFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Plamen S BozhinovFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Daniel VittFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Hella KohlhofFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Jason SlizgiFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Matej OndrusFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Valentina SciaccaFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Andreas R MuehlerFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
EMPhASIS investigatorsFrom the Mellen Center for Multiple Sclerosis (R.J.F.), Cleveland Clinic, OH; Department of Neurology with Institute of Translational Neurology (H.W.), University of Münster, Germany; Lycalis sprl (C.W.), Brussels, Belgium; Department of Medicine (N.D.S.), Surgery and Neuroscience, University of Siena, Italy; Department of Neurology (J. Sellner), Landesklinikum Mistelbach-Gänserndorf, Austria; Regional Clinical Hospital Department of Vascular Neurology (V.G.), Ivano-Frankivsk, Ukraine; Department of Neurology (K.R.), Medical University of Lublin, Lublin, Poland; Medical University of Pleven (P.S.B.), Bulgaria; Immunic AG (D.V., H.K., M.O., V.S., A.R.M.), Gräfelfing, Germany; and independent consultant (J. Slizgi), Raleigh, NC.
Institute of Clinical Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesVidofludimus calcium suppressed MRI disease activity compared with placebo in patients with relapsing-remitting multiple sclerosis (RRMS) in the first cohort of the phase 2 EMPhASIS study. Because 30 mg and 45 mg showed comparable activity on multiple end points, the study enrolled an additional low-dose cohort to further investigate a dose-response relationship.

methodsIn a randomized, placebo-controlled, phase 2 trial, patients with RRMS, aged 18-55 years, and with ≥2 relapses in the last 2 years or ≥1 relapse in the last year, and ≥1 gadolinium-enhancing brain lesion in the last 6 months. Patients were randomly assigned (1:1:1) vidofludimus calcium (30 or 45 mg) or placebo in cohort 1 and vidofludimus calcium (10 mg) or placebo (4:1) in cohort 2 for 24 weeks. The primary end point was the cumulative number of combined unique active (CUA) lesions at week 24. Secondary end points were clinical outcomes and safety.

resultsAcross cohorts 1 and 2, 268 patients were randomized to placebo (n = 81), 10 mg (n = 47) vidofludimus calcium, 30 mg (n = 71) vidofludimus calcium, or 45 mg (n = 69) vidofludimus calcium. The mean cumulative CUA lesions over 24 weeks was 5.8 (95% CI 4.1-8.2) for placebo, 5.9 (95% CI 3.9-9.0) for 10 mg treatment group, 1.4 (95% CI 0.9-2.1) for 30 mg treatment group, and 1.7 (95% CI 1.1-2.5) for 45 mg treatment group. Serum neurofilament light chain decreased in a dose-dependent manner. The number of patients with confirmed disability worsening after 24 weeks was 3 (3.7%) patients receiving placebo and 3 (1.6%) patients receiving any dose of vidofludimus calcium. Treatment-emergent adverse events occurred in 35 (43%) placebo patients compared with 11 (23%) and 71 (37%) patients in the 10 mg or any dose of vidofludimus calcium groups, respectively. The incidence of liver enzyme elevations and infections were similar between placebo and any dose of vidofludimus calcium. No new safety signals were observed. DISCUSSION: Compared with placebo, vidofludimus calcium suppressed the development of new brain lesions with daily doses of 30 mg and 45 mg, but not 10 mg, establishing the lowest efficacious dose is 30 mg. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among adults with active RRMS and ≥1 Gd+ brain lesion in the past 6 months, the cumulative number of active lesions decreased with vidofludimus calcium. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov (NCT03846219) and EudraCT (2018-001896-19).

Indexed as

Dose-Response Relationship, DrugMultiple Sclerosis, Relapsing-RemittingAdolescentAdultDouble-Blind MethodFemaleHumansMaleMiddle AgedYoung Adult

Identifiers

PMID38662979
PMCPMC11087024
OpenAlexW4395475247

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.