Multiple Sclerosis, Relapsing-RemittingPhase 3ENSURE-2NCT05201638
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, Relapsing-Remitting, run by Immunic AG at 101 sites in 14 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-2) Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Multiple Sclerosis, Relapsing-Remitting
- 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
- 1,100 participants
- Where
- 101 sitesin 14 countries
- Study dates
- 12 Jan 2022to Oct 2033
- Phase
- Phase 3
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
Show all 9Show fewer
- 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 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.
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
101 sites in 14 countries.
101 sites in 14 countries
Russia25 sites
Arkhangelsk Regional Clinical Hospital
Arkhangelsk, 163045
Kazan State Medical Academy (Polyclinic) / Federal State Budgetary Educational Institution of Supplementary Professional Education "Russian medical academy of continuous professional education" of the Ministry of Health of the Russian Federation
Kazan', 420061
Kuzbass regional clinical hospital n.a. S.V.Belyaev
Kemerovo, 650066
Budgetary Institution of Khanty-Mansiysk Autonomous District-Yugra "Regional Clinical Hospital"
Khanty-Mansiysk, 628012
Federal State Budgetary Educational Institution of Higher Education "Kirov State Medical University" of the Ministry of Healthcare of the Russian Federation
Kirov, 610998
State Budgetary healthcare Institution of Moscow City "City Policlinic 2 of the Healthcare Department of Moscow City"
Moscow, 117556
First Moscow State Medical University n.a. I.M. Sechenov
Moscow, 119021
Federal Scientific Clinical Centre of Physical-Chemical Medicine of the Federal Medial Biological Agency
Moscow, 119992
Russian Сenter of Neurology and Neurosciences, RCNN;
Moscow, 125367
Privolzhsky Federal Medical University of Ministry of Health of the Russian Federation
Nizhny Novgorod, 603155
Siberian District Medical Center
Novosibirsk, 630007
Rostov State Medical Unevrsity
Rostov-on-Don, 344022
LLC Praximed
Saint Petersburg, 194223
Leningrad Regional Hospital
Saint Petersburg, 194291
1st St Petersburg State Medical University
Saint Petersburg, 197022
St. Petersburg State Budgetary Healthcare Institution "City Clinical Hospital No. 31"
Saint Petersburg, 197110
Institute of the human brain of the Russian Academy of Sciences n.a. N.P. Bekhtereva
Saint Petersburg, 197376
City Hospital 40
Saint Petersburg, 197706
Samara regional clinical hospital n. a. V. L. Seredavin
Samara, 443095
Republican Clinical Hospital #4
Saransk, 430032
Smolensk Regional Clinical Hospital
Smolensk, 214019
Nebbiolo Center for Clinical Trials
Tomsk, 634009
Medical Unit "Neftianik"
Tyumen, 625048
Republican Clinical Hospital named after G.G. Kuvatov
Ufa, 450005
Ulyanovsk regional clinical hospital
Ulyanovsk, 432017
Ukraine18 sites
Communal noncommercial enterprise "First Cherkasy City Hospital"
Cherkasy, 18009
MS Diagnosis Treatment Center
Cherkasy
Chernihiv City Hospital 4
Chernihiv
Municipal Institution "Dnipropetrovsk Regional Rehabilitation Hospital" of Dnipropetrovsk Regional Council"
Dnipro, 49000
Ukrainian State Research Institute of Medico-Social Problems of Disability
Dnipro, 49027
"University Clinic" of Dnipro State Medical University, Department of Neurology
Dnipro, 49038
Dnipro City Hospital 6
Dnipro
Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1
Kremenchuk, 39623
State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine
Kyiv, 03115
1 Private Clinic Medical Center
Kyiv
Dopomoga Plus medical center
Kyiv
Volyn Reg Clin Hospital
Lutsk, 43005
Lviv Regional Central Hospital
Lviv, 79010
5 City Clin Hospital
Lviv, 79013
Communal institution "City Clinical Hospital №3" of Poltava City Council
Poltava, 36000
City Clinical Hospital 2
Rivne
Sumy Reg Clinical Hospital
Sumy
Salutem
Vinnytsia, 21018
Turkey (Türkiye)13 sites
Adana Baskent Hospital
Adana, 01250
Uludag University Hospital
Bursa, 16059
Bursa Yuksek Ihtisas Eğitim Ve Araştırma Hastanesi
Bursa, 16140
Bezmialem Vakif University Hospital
Istanbul, 34093
T.C. Ministry of Health Istanbul Haseki Training and Research Hospital
Istanbul, 34250
Sancaktepe Sehit Prof.Dr. Ilhan Varank Training and Research Hospital
Istanbul, 34785
Haydar Pasa Num. EAH
Istanbul
Kocaeli University Research and Application Hospital
Kocaeli, 41000
Kutahya Uni Evliya Celebi Hspt
Kütahya, 43040
Manisa Celal Bayar University Hafsa Sultan Hospital
Manisa, 45030
Sakarya Egitim ve Arastirma Hast
Sakarya, 54100
19 Mayis University Medical Faculty Hospital Health Application and Research Center
Samsun, 55200
Namik Kemal Uni Hospital
Tekirdağ, 59100
Serbia10 sites
Klinicko bolnicki centar Dr Dragisa Misovic - Dedinje
Belgrade, 11000
Klinicko bolnicki centar Zvezdara
Belgrade, 11000
Vojnomedicinska akademija
Belgrade, 11000
Univerzitetski Klinicki centar Kragujevac
Kragujevac, 34000
General Hospital Leskovac
Leskovac, 16000
Univerzitetski Klinicki centar Nis
Niš, 18000
Hsptl Sveti Vracevi
Novi Kneževac
General Hospital Uzice
Užice, 31000
Klinicko Bolnicki centar Zemun
Zemun, 11080
Opsta bolnica Djordje Jovanovic Zrenjanin
Zrenjanin, 23000
Poland9 sites
NZOZ Novo-Med
Katowice, 40-584
NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"
Katowice, 40123
Neuro-Medic Janusz Zbrojkiewicz
Katowice, 40686
NZOZ Neuromed
Lublin, 20-064
Indywidualna Praktyka Lekarska prof. Konrad Rejdak
Lublin, 20-410
NZOZ Hertmanowskiej
Plewiska, 62-064
NZOZ Neuro-Kard
Poznan, 61-853
Centrum Medyczne NeuroProtect
Warsaw, 01684
Centrum Med. Ibismed
Zabrze
India7 sites
Post-Graduation Institute of Medical Education and Research (PGIMER)
Chandigarh, 160012
North East Healthcare Pvt Ltd (Marengo Asia Hospitals, Gurugram)
Haryāna, 122011
Dr Ram Manohar Lohia Institute of Medical Sciences
Lucknow, 226010
All India Institute of Medical Sciences
New Delhi, 110029
GB Pant Institute of Postgraduate Medical Education and Research
New Delhi, 110056
SRI Guru Ram Das Institute of Medical Sciences and Research
Punjābi Bāgh, 143006
Vasudev Multi-Speciality Hospital
Raipur, 492013
Bosnia and Herzegovina6 sites
UCC of Rep of Srpska
Banja Luka
Cantonal Hospital Bihac Dr. Irfan Ljubijankic
Bihać, 77000
University Clinical Hospital Mostar
Mostar, 88000
University Clinical Center of Sarajevo
Sarajevo, 71000
University Clinical Center Sarajevo
Sarajevo, 71000
University Clinical Center Tuzla
Tuzla, 75000
Romania4 sites
Clubul Sanatatii SRL
Campulung Muscel, 115100
Spitalul clinic CF Constanta
Constanța, 900123
Spitalul Judetean de Urgenta Piatra Neamt
Piatra Neamţ, 610136
Aria Clinic SRL
Sibiu, 550052
Armenia3 sites
Heratsi Hospital Complex 1
Yerevan, 0025
Saint Gregory the Illuminator Medical Center
Yerevan, 0056
Erebouni Medical Center
Yerevan, 0087
United States2 sites
Neuro of Central Florida
Altamonte Springs, Florida, 32714
Healthcare Innovations
Coral Springs, Florida, 33067
Germany1 site
University Hospital Muenster, Institute Translational Neurology dept. Neurology
Münster, 48149
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-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)
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: 72 weeks (approximately 15 months) Open Label Extension Period: Up to approximately 8 years
- Conditions
- Multiple Sclerosis, Relapsing-Remitting
- Being tested
- IMU-838 tablets, Placebo matching IMU-838 tablets
- 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.
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 based on 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 by assessment of occurrence of Adverse Events.
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 posted21 Jan 2022
- Study start12 Jan 2022
- Primary completionNov 2026 (estimated)
- Study completionOct 2033 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple Sclerosis, Relapsing-RemittingStudies 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
- 1,100 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
- NCT05201638
- Sponsor's protocol ID
- P3-IMU-838-RMS-02
- Acronym
- ENSURE-2
- Status last verified
- Sep 2026
- First submitted
- 13 Dec 2021
- Last updated
- 1 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No