Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis (ENSURE-1)

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-1)

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-1)

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: Up to 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years

Study Type

Interventional

Enrollment (Actual)

1121

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

  • Albania
      • Tirana, Albania, 1005
        • Klinika Mjekesore Nuova, Neurology Clinic
      • Tirana, Albania
        • Hygeia Hospital Tirana
  • Algeria
      • Algiers, Algeria, 16000
        • University Hospital Center Mustapha Pacha, Algiers
      • Annaba, Algeria, 23000
        • University Hospital Center Ibn Sina, Annaba
      • Oran, Algeria, 31000
        • University Hospital Center of Oran
  • Bulgaria
      • Blagoevgrad, Bulgaria, 2700
        • MHAT Puls AD
      • Burgas, Bulgaria, 8000
        • MHAT "Heart and Brain", EAD
      • Pleven, Bulgaria, 5800
        • MC Exacta Medica OOD
      • Pleven, Bulgaria, 5800
        • MHAT Avis Medica
      • Pleven, Bulgaria, 5800
        • UMHAT Dr.Georgi Stranski EAD
      • Pleven, Bulgaria
        • Heart and Brain University Hospital
      • Pleven, Bulgaria
        • MC Vita 1
      • Plovdiv, Bulgaria, 4002
        • UMHAT Sveti Georgi
      • Plovdiv, Bulgaria, 4001
        • UMHAT "Kaspela"EOOD
      • Plovdiv, Bulgaria, 4002
        • UMHAT "Pulmed" Ltd
      • Rousse, Bulgaria
        • UMHAT "Medica Ruse"
      • Sofia, Bulgaria, 1431
        • UMHAT "Alexandrovska"
      • Sofia, Bulgaria, 1431
        • UMHAT "Alexandrovska" EAD
      • Sofia, Bulgaria
        • Military Medical Academy
      • Sofia, Bulgaria, 1606
        • Military Medical Academy MHAT
      • Sofia, Bulgaria, 1000
        • CCB Medical Institute Ministry of Interior
      • Sofia, Bulgaria, 1000
        • Diagnostic and Consultative Center Neoclinic
      • Sofia, Bulgaria, 1000
        • UMHAT "Sveti Ivan Rilski" EAD
      • Sofia, Bulgaria, 1113
        • MHATNP "Sveti Naum", EAD
      • Sofia, Bulgaria, 1113
        • MHATNPsy Sveti Naum EAD
      • Sofia, Bulgaria, 1618
        • MHAT "Sveta Sofia" EOOD
      • Sofia, Bulgaria
        • UMHAT"Tsaritsa Yoanna -ISUL
      • Sofia, Bulgaria
        • UMHATEM N.Pirogov
      • Varna, Bulgaria
        • UMHAT "Sveta Marina" EAD, First Clinic of Neurological Diseases
  • Georgia
      • Tbilisi, Georgia
        • LTD Aversi Clinic
      • Tbilisi, Georgia, 0141
        • 1st Uni Clinic of Tbilisi LEPL
      • Tbilisi, Georgia
        • Eristavi Experimental Center
      • Tbilisi, Georgia
        • J.S.C. Curatio Clinic
      • Tbilisi, Georgia
        • Katsiashvili Emergency Center
      • Tbilisi, Georgia
        • Khechinashvili University Hospital
      • Tbilisi, Georgia
        • LTD New Hospitals
      • Tbilisi, Georgia
        • MediClub Georgia LLC
      • Tbilisi, Georgia
        • Pineo Medical Ecosystem LTD
      • Tbilisi, Georgia
        • Sarajishvili Neurology Institute
  • Germany
      • Münster, Germany, 48149
        • University Hospital Muenster, Institute Translational Neurology dept. Neurology
  • India
      • Bangalore, India, 560092
        • Medstar Speciality Hospital
      • Mangalore, India, 575002
        • Mallikatte, Kadri
      • Nagpur, India
        • Jasleen Hospital
      • New Delhi, India, 110060
        • Sir Ganga Ram Hospital
      • Pune, India, 411001
        • Ruby Hospital
      • Shimla, India, 171001
        • Indira Gandhi Medical College & Hospital
      • Varanasi, India, 221005
        • Institute of Medical Sciences Banaras Hindu University,IMS BHU Varanasi
  • Jordan
      • Amman, Jordan, 11942
        • Jordan University Hospital
      • Amman, Jordan, 11196
        • Istiklal Hospital
      • Amman, Jordan
        • TSH Advanced Clinical Center
      • Irbid, Jordan
        • Irbid Speciality Hospital
  • Lebanon
      • Beirut, Lebanon
        • Hotel Dieu de France Hospital
      • Hamra, Lebanon, 1107-2020
        • AUB Medical Center
  • Lithuania
      • Kaunas, Lithuania, 50161
        • Lietuvos Sveikatos Mokslu Universitetas - Kauno Klinikos
  • Mexico
      • Culiacán, Mexico, 80020
        • Neurociencias Estudios Clínicos S.C
      • Guadalajara, Mexico, 44670
        • Instituto Jalisciense de Metabolismo, SC
      • Mexico City, Mexico, 03310
        • Grupo Medico Camino SC
      • Mexico City, Mexico, 06700
        • Cliditer S.A de C.V
      • Mexico City, Mexico, 14050
        • Unidad de Investigacion en Salud de Chihuahua S.C.
      • Mexico City, Mexico
        • Clinstile SA de CV
      • Morelia, Mexico, 58000
        • Centro de Morelia
      • Veracruz, Mexico, 91900
        • Sociedad de Metabolismo y Corazon, S.C.
      • Veracruz, Mexico, 91900
        • Faicic de RL de CV
  • Moldova
      • Chisinau, Moldova
        • Instititute of Emergency Medicine
      • Chisinau, Moldova
        • Medico-Sanitary Public Institution, Institute of Neurology and Neurosurgery "Diomid Gherman"
      • Chisinau, Moldova
        • The Diomid Gherman Institute of Neurology and Neurosurgery
  • Montenegro
      • Nikšić, Montenegro
        • General Hospital Niksic
      • Podgorica, Montenegro
        • Clinical Center of Montenegro
  • North Macedonia
      • Skopje, North Macedonia
        • Hospital "8 mi Septemvri"
      • Skopje, North Macedonia
        • University Clinic of Neurology
  • Poland
      • Lublin, Poland, 20-064
        • NZOZ Neuromed M. i M. Nastaj Sp. P.
  • Ukraine
      • Chernihiv, Ukraine, 14029
        • Communal Non-Commercial Enterprise "Chernihiv Regional Hospital",Department of Neurology
      • Chernivtsi, Ukraine, 58023
        • Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"
      • Chernivtsi, Ukraine
        • Chernihiv Regional Hospital
      • Ivano-Frankivsk, Ukraine, 76008
        • Regional Clinical Hospital
      • Ivano-Frankivsk, Ukraine, 76493
        • Neuro Global, LLC
      • Khmelnytskyi, Ukraine
        • Khmelnytsky regional hospital of war veterans
      • Kiev, Ukraine
        • Clinical Hospital #15 of the Podilskyi District of the Kyiv City
      • Kyiv, Ukraine, 3037
        • "Medbud"
      • Kyiv, Ukraine, 4212
        • SMART medical center
      • Kyiv, Ukraine
        • Kyiv City Hospital 4
      • Odesa, Ukraine
        • Odesa Regional Clinical Hospital, Department of Neurosurgery
      • Poltava, Ukraine
        • Medical and diagnostic center of a LLC "Medcontinent", neurology and rehabilitation center
      • Ternopil, Ukraine, 46027
        • Ternopil Psycho-Neuro Hospital
      • Uzhhorod, Ukraine
        • Regional Clinical Center for Neurosurgery and Neurology
  • United States
    • Arizona
      • Phoenix, Arizona, United States, 85004
        • Xenoscience, Inc., 21st Century Neurology
    • California
      • West Hollywood, California, United States, 90048
        • Regina Berkovich MD, PhD Inc. MS Neurology
    • Florida
      • Bradenton, Florida, United States, 34205
        • Bradenton Research Center
      • Naples, Florida, United States, 34105
        • Collier Neurologic Specialists
      • Ormond Beach, Florida, United States, 32174
        • Neurology Associates of Ormond Beach
    • Illinois
      • Northbrook, Illinois, United States, 60062
        • Consultants in Neurology, Ltd

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

14 years to 51 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 ofCOVID-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 regarding 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 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 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
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 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
Safety of IMU-838 versus placebo
Time Frame: 72 weeks
To evaluate safety and tolerability of IMU-838 versus placebo by assessing rates of Treatment Emergent Adverse Events, Adverse Events of Special Interest, Serious Adverse Events, changes in levels of pre-specified laboratory parameters, vital signs and ECG parameters and rates and reasons for study discontinuations.
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)

November 18, 2021

Primary Completion (Estimated)

November 1, 2026

Study Completion (Estimated)

September 1, 2033

Study Registration Dates

First Submitted

September 30, 2021

First Submitted That Met QC Criteria

November 19, 2021

First Posted (Actual)

November 26, 2021

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-01

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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