Multiple SclerosisPhase 3ENSURE-1NCT05134441
Study to Evaluate the Efficacy, Safety, and Tolerability of IMU-838 in Patients With Relapsing Multiple Sclerosis
A Phase 3 study testing IMU-838 tablets in people with Multiple Sclerosis, run by Immunic AG at 103 sites in 17 countries.
Trial summary
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) Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- IMU-838 tablets
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,121 participants
- Where
- 103 sitesin 17 countries
- Study dates
- 18 Nov 2021to Sep 2033
- Phase
- Phase 3
- 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 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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:
- At least 2 relapses in the last 24 months before randomization, or
- At least 1 relapse in the last 12 months before randomization, or
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- 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.
Who cannot join
- 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.
Show all 14Show fewer
- 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
Trial locations and contacts
103 sites in 17 countries.
103 sites in 17 countries
Bulgaria24 sites
MHAT Puls AD
Blagoevgrad, 2700
MHAT "Heart and Brain", EAD
Burgas, 8000
MC Exacta Medica OOD
Pleven, 5800
MHAT Avis Medica
Pleven, 5800
UMHAT Dr.Georgi Stranski EAD
Pleven, 5800
Heart and Brain University Hospital
Pleven
MC Vita 1
Pleven
UMHAT "Kaspela"EOOD
Plovdiv, 4001
UMHAT "Pulmed" Ltd
Plovdiv, 4002
UMHAT Sveti Georgi
Plovdiv, 4002
UMHAT "Medica Ruse"
Rousse
CCB Medical Institute Ministry of Interior
Sofia, 1000
Diagnostic and Consultative Center Neoclinic
Sofia, 1000
UMHAT "Sveti Ivan Rilski" EAD
Sofia, 1000
MHATNP "Sveti Naum", EAD
Sofia, 1113
MHATNPsy Sveti Naum EAD
Sofia, 1113
UMHAT "Alexandrovska" EAD
Sofia, 1431
UMHAT "Alexandrovska"
Sofia, 1431
Military Medical Academy MHAT
Sofia, 1606
MHAT "Sveta Sofia" EOOD
Sofia, 1618
Military Medical Academy
Sofia
UMHAT"Tsaritsa Yoanna -ISUL
Sofia
UMHATEM N.Pirogov
Sofia
UMHAT "Sveta Marina" EAD, First Clinic of Neurological Diseases
Varna
Ukraine14 sites
Communal Non-Commercial Enterprise "Chernihiv Regional Hospital",Department of Neurology
Chernihiv, 14029
Regional Municipal Non-commercial Enterprise "Chernivtsi Emergency Medical Hospital"
Chernivtsi, 58023
Chernihiv Regional Hospital
Chernivtsi
Regional Clinical Hospital
Ivano-Frankivsk, 76008
Neuro Global, LLC
Ivano-Frankivsk, 76493
Khmelnytsky regional hospital of war veterans
Khmelnytskyi
Clinical Hospital #15 of the Podilskyi District of the Kyiv City
Kiev
"Medbud"
Kyiv, 3037
SMART medical center
Kyiv, 4212
Kyiv City Hospital 4
Kyiv
Odesa Regional Clinical Hospital, Department of Neurosurgery
Odesa
Medical and diagnostic center of a LLC "Medcontinent", neurology and rehabilitation center
Poltava
Ternopil Psycho-Neuro Hospital
Ternopil, 46027
Regional Clinical Center for Neurosurgery and Neurology
Uzhhorod
Russia12 sites
City Hospital #5, Barnaul
Barnaul, 656045
Profimed LLC
Barnaul, 656906
Bryansk Regional Hospital 1
Bryansk, 241033
Regional Clinical Hospital 3
Chelyabinsk, 454021
Federal Siberian Scientific and Clinical Centre of Federal Medical and Biological Agency
Krasnoyarsk, 660037
Kursk Regional Clinical Hospital
Kursk, 305007
Medis LLC
Nizhny Novgorod, 603076
Sibneiromed LLC
Novosibirsk, 630004
SDMCH SDMC of FMBA of Russia
Novosibirsk, 630007
Perm State Medical University n.a. Acad. E. A. Vagner
Perm, 614045
Samara regional clinical hospital n. a. V. L. Seredavin
Samara, 443095
Sverdlovsk Regional Clinical Hospital #1
Yekaterinburg, 620102
Georgia10 sites
1st Uni Clinic of Tbilisi LEPL
Tbilisi, 0141
Eristavi Experimental Center
Tbilisi
J.S.C. Curatio Clinic
Tbilisi
JSC "Jerarsi"
Tbilisi
Khechinashvili University Hospital
Tbilisi
LTD Aversi Clinic
Tbilisi
LTD New Hospitals
Tbilisi
MediClub Georgia LLC
Tbilisi
Pineo Medical Ecosystem LTD
Tbilisi
Sarajishvili Neurology Institute
Tbilisi
Mexico9 sites
Neurociencias Estudios Clínicos S.C
Culiacán, 80020
Instituto Jalisciense de Metabolismo, SC
Guadalajara, 44670
Grupo medico camino SC
Mexico City, 03310
Consultorio Médico Expert Brain Clinic
Mexico City, 06700
Unidad de Investigación en Salud de Chihuahua S.C.
Mexico City, 14050
Clinstile SA de CV
Mexico City
Centro de Morelia
Morelia, 58000
Faicic de RL de CV
Veracruz, 91900
Sociedad de Metabolismo y Corazon, S.C.
Veracruz, 91900
India7 sites
Medstar Speciality Hospital
Bangalore, 560092
Mallikatte, Kadri
Mangalore, 575002
Jasleen Hospital
Nagpur
Sir Ganga Ram Hospital
New Delhi, 110060
Ruby Hospital
Pune, 411001
Atal Institute of Medical Super Specialities (AIMSS)
Shimla, 171006
Institute of Medical Sciences Banaras Hindu University,IMS BHU Varanasi
Varanasi, 221005
United States6 sites
Bradenton Research Center
Bradenton, Florida, 34205
Collier Neurologic Specialists
Naples, Florida, 34105
Consultants in Neurology, Ltd
Northbrook, Illinois, 60062
Neurology Associates of Ormond Beach
Ormond Beach, Florida, 32174
Xenoscience, Inc., 21st Century Neurology
Phoenix, Arizona, 85004
Regina Berkovich MD, PhD Inc. MS Neurology
West Hollywood, California, 90048
Jordan4 sites
Istiklal Hospital
Amman, 11196
Jordan University Hospital
Amman, 11942
TSH Advanced Clinical Center
Amman
Irbid Speciality Hospital
Irbid
Algeria3 sites
University Hospital Center Mustapha Pacha, Algiers
Algiers, 16000
University Hospital Center Ibn Sina, Annaba
Annaba, 23000
University Hospital Center of Oran
Oran, 31000
Moldova3 sites
Instititute of Emergency Medicine
Chisinau
Medico-Sanitary Public Institution, Institute of Neurology and Neurosurgery "Diomid Gherman"
Chisinau
The Diomid Gherman Institute of Neurology and Neurosurgery
Chisinau
Albania2 sites
Klinika Mjekesore Nuova, Neurology Clinic
Tirana, 1005
Hygeia Hospital Tirana
Tirana
Lebanon2 sites
Hotel Dieu de France Hospital
Beirut
AUB Medical Center
Hamra, 1107-2020
Montenegro2 sites
General Hospital Niksic
Nikšić
Clinical Center of Montenegro
Podgorica
North Macedonia2 sites
Hospital "8 mi Septemvri"
Skopje
University Clinic of Neurology
Skopje
Germany1 site
University Hospital Muenster, Institute Translational Neurology dept. Neurology
Münster, 48149
Lithuania1 site
Lietuvos Sveikatos Mokslu Universitetas - Kauno Klinikos
Kaunas, 50161
About this study
Official title: 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)
Read the 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
- Conditions
- Multiple Sclerosis
- Being tested
- IMU-838 tablets, Placebo matching IMU-838 tablets
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IMU-838 tabletsDrug
Also called vidofludimus calcium
Patients are randomized to IMU-838 or placebo in ratio 1:1
Placebo matching IMU-838 tabletsDrug
Also called Placebo matching vidofludimus calcium
Patients are randomized to IMU-838 or placebo in ratio 1:1
| Study group | Role | What they receive |
|---|---|---|
| IMU-838 | Experimental | 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. Receives: Drug: IMU-838 tablets |
| Placebo | Placebo comparator | Matching placebo, as described for the test product, identical number of tablets as given for IMU-838. Receives: Drug: Placebo matching IMU-838 tablets |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate efficacy of IMU-838 versus placebo regarding time to first relapse
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.
Measured: 72 weeks
Secondary outcomes (5)
Effect of IMU-838 versus placebo on volume of new T2 lesions
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.
Measured: 72 weeks
Effect of IMU-838 versus placebo on disability progression
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.
Measured: 72 weeks
Effect of IMU-838 versus placebo on cognitive performance
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.
Measured: 72 weeks
Effect of IMU-838 versus placebo on whole brain atrophy
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.
Measured: 72 weeks
Safety of IMU-838 versus placebo
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.
Measured: 72 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Nov 2021
- Study start18 Nov 2021
- Primary completionNov 2026 (estimated)
- Study completionSep 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,121 participants (actual)
Sponsor and investigators
- Lead sponsor
- Immunic AG
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Robert J. Fox, MD, Principal investigator, Mellen Center for MS, Neurological Institute, Cleveland Clinic, Ohio
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05134441
- Sponsor's protocol ID
- P3-IMU-838-RMS-01
- Acronym
- ENSURE-1
- Status last verified
- Sep 2026
- First submitted
- 30 Sep 2021
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Pemba CM, Sakurai Y, Kurosaki Y, Patten JJ, Amalia E, Inaoka DK, Davey RA, Shiba T, Kita K, Yasuda J. Antiviral activities of ascofuranone and naphthoquinone derivatives against Ebola virus. Antiviral Res. 2026 May;249:106400. doi: 10.1016/j.antiviral.2026.106400. Epub 2026 Mar 31.
PubMed 41933619
Study at a glance
From the registry record, last updated by the sponsor on 1 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT05134441
- Acronym / sponsor ID
- ENSURE-1 / P3-IMU-838-RMS-01
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 1,121 participants (actual)
- Lead sponsor
- Immunic AGIndustry (pharma, biotech, devices)
- Study start
- 18 Nov 2021 (actual)
- Primary completion
- Nov 2026 (estimated)
- Study completion
- Sep 2033 (estimated)
- First posted
- 26 Nov 2021 (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.
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)
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| IMU-838 | Experimental | Drug: IMU-838 tabletsIMU-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. |
| Placebo | Placebo comparator | Drug: Placebo matching IMU-838 tabletsMatching placebo, as described for the test product, identical number of tablets as given for IMU-838. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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:
- Willingness and ability to comply with the protocol.
Key exclusion criteria (14 listed)
- 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
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 |
|---|---|---|
| IMU-838 tabletsAlso: vidofludimus calciumPatients are randomized to IMU-838 or placebo in ratio 1:1 | Drug | IMU-838 |
| Placebo matching IMU-838 tabletsAlso: Placebo matching vidofludimus calciumPatients are randomized to IMU-838 or placebo in ratio 1:1 | Drug | Placebo |
Primary outcome
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.
5 secondary outcomes
Effect of IMU-838 versus placebo on volume of new T2 lesions
Time frame: 72 weeks
Effect of IMU-838 versus placebo on disability progression
Time frame: 72 weeks
Effect of IMU-838 versus placebo on cognitive performance
Time frame: 72 weeks
Effect of IMU-838 versus placebo on whole brain atrophy
Time frame: 72 weeks
Safety of IMU-838 versus placebo
Time frame: 72 weeks
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 1 Oct 2026.
- Derived from this study: PubMed 41933619Pemba CM, Sakurai Y, Kurosaki Y, Patten JJ, Amalia E, Inaoka DK, Davey RA, Shiba T, Kita K, Yasuda J. Antiviral activities of ascofuranone and naphthoquinone derivatives against Ebola virus. Antiviral Res. 2026 May;249:106400. doi: 10.1016/j.antiviral.2026.106400. Epub 2026 Mar 31.
- Individual participant dataSharing planned: No
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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.
Robert J. Fox, MD principal investigator
Mellen Center for MS, Neurological Institute, Cleveland Clinic, Ohio
103 sites in 17 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing IMU-838 tablets in people with Multiple Sclerosis, run by Immunic AG at 103 sites in 17 countries.
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 9 inclusion and 14 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 1 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 103 sites in Bulgaria, Ukraine, Russia, Georgia, Mexico and 12 more countries. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
To evaluate efficacy of IMU-838 versus placebo regarding time to first relapse (time frame: 72 weeks). 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 NCT05134441, which also lists 1 linked publication.
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 1 Oct 2026.