Study to Evaluate the Efficacy, Safety and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis (ENSURE-2)

February 20, 2026 updated by: Immunic AG

A Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 Versus Placebo in Adults With Relapsing Multiple Sclerosis (ENSURE-2)

Multi-Center, Randomized, Double-Blinded Phase 3 Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 versus Placebo in Adults with Relapsing Multiple Sclerosis (ENSURE-2)

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

This study will be a multicenter, randomized, double-blind, placebo-controlled study with a blinded Main Treatment Period (MT) and an Open Label Period (OLE) to evaluate the efficacy, safety, and tolerability of IMU-838 in adult patients with RMS.

The study will consist of the following periods:

Screening Period: Approximately 28 days Main Treatment Period: 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years

Study Type

Interventional

Enrollment (Actual)

1100

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Armenia
      • Yerevan, Armenia, 0087
        • Erebouni Medical Center
      • Yerevan, Armenia, 0025
        • Heratsi Hospital Complex 1
      • Yerevan, Armenia, 0056
        • Saint Gregory the Illuminator Medical Center
  • Bosnia and Herzegovina
      • Banja Luka, Bosnia and Herzegovina
        • UCC of Rep of Srpska
      • Bihać, Bosnia and Herzegovina, 77000
        • Cantonal Hospital Bihac Dr. Irfan Ljubijankic
      • Sarajevo, Bosnia and Herzegovina, 71000
        • University Clinical Center Sarajevo
      • Sarajevo, Bosnia and Herzegovina, 71000
        • University Clinical Center of Sarajevo
      • Tuzla, Bosnia and Herzegovina, 75000
        • University Clinical Center Tuzla
  • Estonia
      • Tallinn, Estonia
        • Astra Clinic
  • Germany
      • Münster, Germany, 48149
        • University Hospital Muenster, Institute Translational Neurology dept. Neurology
  • India
      • Chandigarh, India, 160012
        • Post-Graduation Institute of Medical Education and Research (PGIMER)
      • Gurugramam, India, 122002
        • Fortis Memorial Research Institute
      • Kochi, India, 682025
        • Polakulath Narayanan Renai Medicity MSSH
      • Lucknow, India, 226010
        • Dr Ram Manohar Lohia Institute of Medical Sciences
      • New Delhi, India, 110029
        • All India Institute of Medical Sciences
      • New Delhi, India, 110056
        • GB Pant Institute of Postgraduate Medical Education and Research
      • Punjābi Bāgh, India, 143006
        • Sri Guru Ram Das Institute of Medical Sciences and Research
      • Raipur, India, 492001
        • DKS PGI
  • Peru
      • Lima, Peru, 15003
        • Hospital Nacional Dos de Mayo
  • Poland
      • Katowice, Poland, 40-584
        • NZOZ Novo-Med
      • Katowice, Poland, 40123
        • NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"
      • Katowice, Poland, 40686
        • Neuro-Medic Janusz Zbrojkiewicz
      • Lublin, Poland, 20-064
        • NZOZ Neuromed
      • Lublin, Poland, 20-410
        • Indywidualna Praktyka Lekarska prof. Konrad Rejdak
      • Oświęcim, Poland, 32-600
        • Instytut Zdrowia Boczarska
      • Plewiska, Poland, 62-064
        • NZOZ Hertmanowskiej
      • Poznan, Poland, 61-853
        • NZOZ Neuro-Kard
      • Warsaw, Poland
        • FutureMeds Warszawa Centrum
      • Warsaw, Poland, 01684
        • Centrum Medyczne NeuroProtect
      • Zabrze, Poland
        • Centrum Med. Ibismed
  • Romania
      • Campulung Muscel, Romania, 115100
        • Clubul Sanatatii SRL
      • Constanța, Romania, 900123
        • Spitalul clinic CF Constanta
      • Sibiu, Romania, 550052
        • Aria Clinic SRL
  • Serbia
      • Belgrade, Serbia, 11000
        • Vojnomedicinska Akademija
      • Belgrade, Serbia, 11000
        • Klinicko bolnicki centar Dr Dragisa Misovic - Dedinje
      • Belgrade, Serbia, 11000
        • Kliničko bolnički centar Zvezdara
      • Kragujevac, Serbia, 34000
        • Univerzitetski Klinicki Centar Kragujevac
      • Leskovac, Serbia, 16000
        • General Hospital Leskovac
      • Niš, Serbia, 18000
        • Univerzitetski Klinicki centar Nis
      • Novi Kneževac, Serbia
        • Hsptl Sveti Vracevi
      • Užice, Serbia, 31000
        • General Hospital Uzice
      • Zemun, Serbia, 11080
        • Klinicko Bolnicki centar Zemun
      • Zrenjanin, Serbia, 23000
        • Opsta bolnica Djordje Jovanovic Zrenjanin
  • Turkey (Türkiye)
      • Adana, Turkey (Türkiye), 01250
        • Adana Baskent Hospital
      • Bursa, Turkey (Türkiye), 16059
        • Uludag University Hospital
      • Istanbul, Turkey (Türkiye), 34093
        • Bezmialem Vakif University Hospital
      • Istanbul, Turkey (Türkiye), 34250
        • T.C. Ministry of Health Istanbul Haseki Training and Research Hospital
      • Istanbul, Turkey (Türkiye), 34785
        • Sancaktepe Sehit Prof.Dr. Ilhan Varank Training and Research Hospital
      • Istanbul, Turkey (Türkiye)
        • Haydar Pasa Num. EAH
      • Kocaeli, Turkey (Türkiye), 41000
        • Kocaeli University Research and Application Hospital
      • Kütahya, Turkey (Türkiye), 43040
        • Kutahya Uni Evliya Celebi Hspt
      • Manisa, Turkey (Türkiye), 45030
        • Manisa Celal Bayar University Hafsa Sultan Hospital
      • Sakarya, Turkey (Türkiye), 54100
        • Sakarya Egitim ve Arastirma Hast
      • Samsun, Turkey (Türkiye), 55200
        • 19 Mayis University Medical Faculty Hospital Health Application and Research Center
      • Tekirdağ, Turkey (Türkiye), 59100
        • Namik Kemal Uni Hospital
  • Ukraine
      • Cherkasy, Ukraine, 18009
        • Communal noncommercial enterprise "First Cherkasy City Hospital"
      • Cherkasy, Ukraine
        • MS Diagnosis Treatment Center
      • Chernihiv, Ukraine
        • Chernihiv City Hospital 4
      • Dnipro, Ukraine, 49000
        • Municipal Institution "Dnipropetrovsk Regional Rehabilitation Hospital" of Dnipropetrovsk Regional Council"
      • Dnipro, Ukraine, 49027
        • Ukrainian State Research Institute of Medico-Social Problems of Disability
      • Dnipro, Ukraine, 49038
        • "University Clinic" of Dnipro State Medical University, Department of Neurology
      • Dnipro, Ukraine
        • Dnipro City Hospital 6
      • Kremenchuk, Ukraine, 39623
        • Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1
      • Kyiv, Ukraine, 03115
        • State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine
      • Kyiv, Ukraine
        • 1 Private Clinic Medical Center
      • Kyiv, Ukraine
        • Dopomoga Plus medical center
      • Lutsk, Ukraine, 43005
        • Volyn Reg Clin Hospital
      • Lviv, Ukraine, 79010
        • Lviv Regional Central Hospital
      • Lviv, Ukraine, 79013
        • 5 City Clin Hospital
      • Poltava, Ukraine, 36000
        • Communal institution "City Clinical Hospital №3" of Poltava City Council
      • Rivne, Ukraine
        • City Clinical Hospital 2
      • Sumy, Ukraine
        • Sumy Reg Clinical Hospital
      • Vinnytsia, Ukraine, 21018
        • Salutem
  • United Kingdom
      • Sheffield, United Kingdom
        • Royal Hallamshire Hospital
  • United States
    • Florida
      • Altamonte Springs, Florida, United States, 32714
        • Neuro of Central Florida
      • Coral Springs, Florida, United States, 33067
        • Healthcare Innovations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 55 years (Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Male or female patient (age ≥18 to ≤55 years).
  • Patients with an established diagnosis of MS according to 2017 McDonald Criteria.
  • Patients with RMS comprising of relapsing remitting MS (RRMS) and active secondary progressive MS, both defined according to Lublin criteria 1996 and 2014.

  • Active disease as defined by Lublin 2014 evidenced prior to Screening by:

    1. At least 2 relapses in the last 24 months before randomization, or
    2. At least 1 relapse in the last 12 months before randomization, or
    3. A positive Gd+ MRI scan (brain and/or spine) in the last 12 months prior to randomization.
  • Willingness and ability to comply with the protocol.
  • Written informed consent given prior to any study-related procedure.

Exclusion Criteria:

  • Patients with non-active secondary progressive MS and primary progressive MS.
  • Any disease other than MS that may better explain the signs and symptoms, including history of complete transverse myelitis.
  • Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or myelin oligodendrocyte glycoprotein (MOG)-IgG-associated encephalomyelitis
  • Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease)
  • Use of experimental/investigational drug (with the exception of COVID-19 vaccines approved by emergency use authorization) and/or participation in drug clinical studies within 6 months prior to Screening
  • Previous or current use of MS treatments lifelong, or within a pre-specified time period.
  • Use of the pre-specified concomitant medications.
  • Clinically significantly abnormal and pre-specified lab values.
  • History of chronic systemic infections within 6 months before the date of informed consent.
  • Diagnosis or suspected liver function impairment, which may cause fluctuating liver function tests during this study.
  • Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis.
  • History or clinical diagnosis of gout.
  • History or presence of any major medical or psychiatric illness
  • Substantial medical condition that could create undue risk to the patient, could affect adherence with the study protocol or could undesirably affect study outcomes

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: IMU-838

IMU-838 (vidofludimus calcium), a small molecule inhibitor of DHODH.

Formulation:

Tablets with 15 or 30 mg IMU-838 for once daily oral intake in the morning.
Drug: IMU-838 tablets
Patients are randomized to IMU-838 or placebo in ratio 1:1
Other Names:
  • Vidofludimus calcium
Placebo Comparator: Placebo
Matching placebo, as described for the test product, identical number of tablets as given for IMU-838.
Drug: Placebo matching IMU-838 tablets
Patients are randomized to IMU-838 or placebo in ratio 1:1
Other Names:
  • Placebo matching vidofludimus calcium

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
To evaluate efficacy of IMU-838 versus placebo based on time to first relapse
Time Frame: 72 weeks
Survival analysis of time to first relapse, occurred after the start of study treatment administration and before the end of the double-blind period, censored at a maximum of 72 weeks.
72 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Effect of IMU-838 versus placebo on volume of new T2 lesions
Time Frame: 72 weeks
To evaluate the effect of IMU-838 versus placebo on volume of new T2 lesions. Mean difference between IMU-838 and placebo in changes of the volume of new MRI T2 lesions over 24-weeks of treatment in the double-blind period.
72 weeks
Effect of IMU-838 versus placebo on disability progression
Time Frame: 72 weeks
To evaluate the effect of IMU-838 versus placebo on disability progression. Survival analysis of time to 12-week confirmed disability progression, as measured on Expanded Disability Status Scale during the double-blind period, censored at maximum 72-weeks.
72 weeks
Effect of IMU-838 versus placebo on cognitive performance
Time Frame: 72 weeks
To evaluate the effect of IMU-838 versus placebo on cognitive performance. Survival analysis of time to confirmed clinically relevant changes on Symbol Digit Modalities Test during the double-blind period, censored at maximum 72- weeks.
72 weeks
Effect of IMU-838 versus placebo on whole brain atrophy
Time Frame: 72 weeks
To evaluate the effect of IMU-838 versus placebo on whole brain atrophy. Difference in the mean of the percentage change on the whole brain volume between IMU-838 and placebo during the 72-weeks double-blind period.
72 weeks
Safety of IMU-838 versus placebo
Time Frame: 72 weeks
To evaluate safety and tolerability by assessment of occurrence of Adverse Events.
72 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Immunic AG

Investigators

  • Principal Investigator: Robert J. Fox, MD, Mellen Center for MS, Neurological Institute, Cleveland Clinic, Ohio

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 12, 2022

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

October 1, 2033

Study Registration Dates

First Submitted

December 13, 2021

First Submitted That Met QC Criteria

January 20, 2022

First Posted (Actual)

January 21, 2022

Study Record Updates

Last Update Posted (Actual)

February 23, 2026

Last Update Submitted That Met QC Criteria

February 20, 2026

Last Verified

February 1, 2026

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P3-IMU-838-RMS-02

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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