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

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: Recruiting
• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Intervention / Treatment: Drug: IMU-838 tablets; Drug: Placebo matching IMU-838 tablets

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 (Estimated): 1050
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Andreas Muehler, MD; Phone Number: +49 89 2080 477 00; Email: info@imux.com

Study Locations

• Armenia
  • Yerevan, Armenia, 0087
    • Recruiting
    • Erebouni Medical Center
    • Contact: Nune Yeghiazaryan, Dr.
  • Yerevan, Armenia, 0025
    • Recruiting
    • Heratsi Hospital Complex 1
    • Contact: Yekaterina Hovhannisyan, Dr.
• Bosnia and Herzegovina
  • Banja Luka, Bosnia and Herzegovina
    • Recruiting
    • UCC of Rep of Srpska
    • Contact: Sanja Grgic, Prof.
  • Bihać, Bosnia and Herzegovina, 77000
    • Recruiting
    • Cantonal Hospital Bihac Dr. Irfan Ljubijankic
    • Contact: Muhamed Lepuzanovic, Dr.
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Recruiting
    • University Clinical Center of Sarajevo
    • Contact: Admir Mehicevic, Dr.
  • Sarajevo, Bosnia and Herzegovina, 71000
    • Recruiting
    • University Clinical Center Sarajevo
    • Contact: Enra Suljic, Dr.
  • Tuzla, Bosnia and Herzegovina, 75000
    • Recruiting
    • University Clinical Center Tuzla
    • Contact: Aida Sehanovic, Dr.
• Estonia
  • Tallinn, Estonia
    • Recruiting
    • Astra Clinic
    • Contact: Katrin Gross-Paju, Dr.
• India
  • Chandigarh, India, 160012
    • Recruiting
    • Post-Graduation Institute of Medical Education and Research (PGIMER)
    • Contact: Dheeraj Khurana, Dr.
  • Gurugramam, India, 122002
    • Recruiting
    • Fortis Memorial Research Institute
    • Contact: Praveen Gupta, Dr.
  • Lucknow, India, 226010
    • Recruiting
    • Dr Ram Manohar Lohia Institute of Medical Sciences
    • Contact: Abdul Qavi, Dr.
  • New Delhi, India, 110029
    • Recruiting
    • All India Institute of Medical Sciences
    • Contact: Manjari Triphathi, Dr.
  • New Delhi, India, 110056
    • Recruiting
    • GB Pant Institute of Postgraduate Medical Education and Research
    • Contact: Debashish Chowdhury, Dr.
  • Punjabi Bagh, India, 143006
    • Recruiting
    • SRI Guru Ram Das Institute of Medical Sciences and Research
    • Contact: Dinesh Kumar, Dr.
  • Raipur, India, 492001
    • Recruiting
    • DKS PGI
    • Contact: Abhijeet Kohat, Dr.
• Peru
  • Lima, Peru, 15801
    • Recruiting
    • Centro de Investig. Médicas
    • Contact: Wenzel Duenas Pacheco, Dr.
• Poland
  • Katowice, Poland, 40123
    • Recruiting
    • NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"
    • Contact: Marek Smilowski, Dr.
  • Katowice, Poland, 40686
    • Recruiting
    • Neuro-Medic Janusz Zbrojkiewicz
    • Contact: Janusz Zbrojkiewicz, Dr.
  • Lublin, Poland, 20-064
    • Recruiting
    • NZOZ Neuromed
    • Contact: Marcin Nastaj, Dr.
  • Lublin, Poland, 20-410
    • Recruiting
    • Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
    • Contact: Konrad Rejdak, Prof
  • Oświęcim, Poland, 32-600
    • Recruiting
    • Instytut Zdrowia Boczarska
    • Contact: Magdalena Boczarska-Jedynak, Dr.
  • Plewiska, Poland, 62-064
    • Recruiting
    • NZOZ Hertmanowskiej
    • Contact: Adriana Chelminiak, Dr.
  • Poznań, Poland, 61-853
    • Recruiting
    • NZOZ Neuro-Kard
    • Contact: Jan Ilkowski, Dr.
  • Warsaw, Poland, 01684
    • Recruiting
    • Centrum Medyczne NeuroProtect
    • Contact: Maciej Czarnecki, Dr.
  • Warsaw, Poland
    • Recruiting
    • FutureMeds Warszawa Centrum
    • Contact: Bartosz Otak, Dr.
  • Zabrze, Poland
    • Recruiting
    • Centrum Med. Ibismed
    • Contact: Monika Adamczyk-Sowa, Prof.
• Romania
  • Bucharest, Romania, 011025
    • Recruiting
    • SC Sana Monitoring SRL
    • Contact: Mirela Chiru, Dr.
  • Bucharest, Romania, 011461
    • Recruiting
    • Elias University Emergency Hospital
    • Contact: Christina Panea, Dr.
  • Constanţa, Romania, 900123
    • Recruiting
    • Spitalul clinic CF Constanta
    • Contact: Ana-Maria Ionescu, Dr.
  • Craiova, Romania, 200157
    • Recruiting
    • Asociatia Comunitatea Oamenilor
    • Contact: Iuliu Trifan, Dr.
  • Câmpulung, Romania, 115100
    • Recruiting
    • Clubul Sanatatii SRL
    • Contact: Emilian S. Manescu, Dr.
  • Sibiu, Romania, 550052
    • Recruiting
    • Aria Clinic SRL
    • Contact: Catalin C. Mutu, Dr.
  • Timişoara, Romania, 300425
    • Withdrawn
    • Neuro Therapy
  • Timişoara, Romania, 300723
    • Recruiting
    • Spit Jud Branzeu TIM Neuro
    • Contact: Mihaela Simu, Prof.
• Serbia
  • Belgrade, Serbia, 11000
    • Recruiting
    • Klinicko bolnicki centar Dr Dragisa Misovic - Dedinje
    • Contact: Dragana Kuljic Obradovic, Dr.
  • Belgrade, Serbia, 11000
    • Recruiting
    • Klinicko bolnicki centar Zvezdara
    • Contact: Vera Cvijanovic, Dr.
  • Belgrade, Serbia, 11000
    • Recruiting
    • Opsta bolnica Medicinski sistem Beograd
    • Contact: Miodrag Vujcic, Dr.
  • Belgrade, Serbia, 11000
    • Recruiting
    • Vojnomedicinska akademija
    • Contact: Evica Dincic, Dr.
  • Kragujevac, Serbia, 34000
    • Recruiting
    • Univerzitetski Klinicki centar Kragujevac
    • Contact: Svetlana Miletic Drakulic, Dr.
  • Niš, Serbia, 18000
    • Recruiting
    • Univerzitetski Klinicki centar Nis
    • Contact: Slobodan Vojinovic, Prof.
  • Novi Kneževac, Serbia
    • Recruiting
    • Hsptl Sveti Vracevi
    • Contact: Jovana Stijovic, Dr.
  • Užice, Serbia, 31000
    • Recruiting
    • General Hospital Uzice
    • Contact: Mira Gavric Kezic, Dr.
  • Zemun, Serbia, 11080
    • Recruiting
    • Klinicko Bolnicki centar Zemun
    • Contact: Dusica Smiljanic-Miljkovic, Dr.
  • Zrenjanin, Serbia, 23000
    • Recruiting
    • Opsta bolnica Djordje Jovanovic Zrenjanin
    • Contact: Julijana Filipov, Dr.
• Turkey
  • Adana, Turkey, 01130
    • Recruiting
    • Acibadem Adana Hospital
    • Contact: Cem Ortacbayram, Dr.
  • Adana, Turkey, 01250
    • Recruiting
    • Adana Baskent Hospital
    • Contact: Basak Karakurum Goksel, Prof.
  • Ankara, Turkey, 06490
    • Recruiting
    • Baskent University Ankara Hospital
    • Contact: Munire Kilinc Toprak, Prof.
  • Istanbul, Turkey, 34093
    • Recruiting
    • Bezmialem Vakif University Hospital
    • Contact: Gulsen Akman-Demir, Prof.
  • Istanbul, Turkey, 34899
    • Recruiting
    • Marmara University Pendik Training and Research Hospital
    • Contact: Gulin Sunter, Prof
  • Istanbul, Turkey, 34250
    • Recruiting
    • T.C. Ministry of Health Istanbul Haseki Training and Research Hospital
    • Contact: Belgin Balci, Prof.
  • Istanbul, Turkey, 34785
    • Recruiting
    • Sancaktepe Sehit Prof.Dr. Ilhan Varank Training and Research Hospital
    • Contact: Serkan Demir, Prof.
  • Istanbul, Turkey
    • Recruiting
    • Haydar Pasa Num. EAH
    • Contact: Recai Türkoğlu, Prof.
  • Kocaeli, Turkey, 41000
    • Recruiting
    • Kocaeli University Research and Application Hospital
    • Contact: Husnu Efendi, Prof.
  • Kütahya, Turkey, 43100
    • Recruiting
    • T.C. Ministry of Health Kutahya Provincial Directorate of Health Kutahya University of Health Sciences Evliya Celebi Training and Research Hospital
    • Contact: Sibel Canbaz Kabay, Prof.
  • Manisa, Turkey, 45030
    • Recruiting
    • Manisa Celal Bayar University Hafsa Sultan Hospital
    • Contact: Hikmet Yilmaz, Prof.
  • Samsun, Turkey, 55200
    • Recruiting
    • 19 Mayis University Medical Faculty Hospital Health Application and Research Center
    • Contact: Murat Terzi, Prof.
  • Tekirdağ, Turkey, 59100
    • Recruiting
    • Namik Kemal Uni Hospital
    • Contact: Aysun Ünal, Prof.
  • Zonguldak, Turkey, 67000
    • Recruiting
    • Zonguldak Bulent Ecevit University Health Practice and Research Hospital
    • Contact: Bilge Piri Cinar, Prof.
• Ukraine
  • Cherkasy, Ukraine
    • Recruiting
    • MS Diagnosis Treatment Center
    • Contact: Valentyna Drobotenko, Dr.
  • Cherkasy, Ukraine, 18009
    • Active, not recruiting
    • Communal noncommercial enterprise "First Cherkasy City Hospital"
  • Chernihiv, Ukraine
    • Recruiting
    • Chernihiv City Hospital 4
    • Contact: Larysa Kadina, Dr.
  • Dnipro, Ukraine
    • Recruiting
    • Dnipro City Hospital 6
    • Contact: Larysa Zakharova, Dr.
  • Dnipro, Ukraine, 49027
    • Active, not recruiting
    • Ukrainian State Research Institute of Medico-Social Problems of Disability
  • Dnipro, Ukraine, 49038
    • Active, not recruiting
    • "University Clinic" of Dnipro State Medical University, Department of Neurology
  • Dnipro, Ukraine, 49000
    • Recruiting
    • Municipal Institution "Dnipropetrovsk Regional Rehabilitation Hospital" of Dnipropetrovsk Regional Council"
    • Contact: Roman Khaitov, Dr.
  • Kremenchuk, Ukraine, 39623
    • Recruiting
    • Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1
    • Contact: Iryna Piskunova, Dr.
  • Kyiv, Ukraine
    • Recruiting
    • 1 Private Clinic Medical Center
    • Contact: Iryna Ihnatenko, Dr.
  • Kyiv, Ukraine
    • Active, not recruiting
    • Dopomoga Plus medical center
  • Kyiv, Ukraine, 03115
    • Recruiting
    • State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine
    • Contact: Olena Kolosynska, Prof.
  • Luts'k, Ukraine, 43005
    • Active, not recruiting
    • Volyn Reg Clin Hospital
  • Lviv, Ukraine, 79010
    • Active, not recruiting
    • Lviv Regional Central Hospital
  • Lviv, Ukraine, 79013
    • Active, not recruiting
    • 5 City Clin Hospital
  • Poltava, Ukraine, 36000
    • Recruiting
    • Communal institution "City Clinical Hospital №3" of Poltava City Council
    • Contact: Svetlana Ivashchenko, Dr.
  • Rivne, Ukraine
    • Active, not recruiting
    • City Clinical Hospital 2
  • Sumy, Ukraine
    • Recruiting
    • Sumy Reg Clinical Hospital
    • Contact: Oleksii Kmyta, Dr.
  • Vinnytsia, Ukraine, 21018
    • Recruiting
    • Salutem
    • Contact: Sergii Moskovko, Dr.
  • Zaporizhzhya, Ukraine, 69001
    • Active, not recruiting
    • LCC Medical center INET-09
  • Zaporizhzhya, Ukraine
    • Active, not recruiting
    • Zaporizhia Med
  • Zaporizhzhya, Ukraine
    • Active, not recruiting
    • Zaporizhia Regional Clinic Hospital
  • Zaporizhzhya, Ukraine
    • Active, not recruiting
    • Zaporizhzhya City Hospital 6
  • Zaporizhzhya, Ukraine
    • Active, not recruiting
    • Zaporizhzhya Hospital 9
• United Kingdom
  • Exeter, United Kingdom, EX2 5DW
    • Recruiting
    • Royal Devon Uni NHS
    • Contact: Timothy Harrower, Dr.
  • Sheffield, United Kingdom
    • Recruiting
    • Royal Hallamshire Hospital
    • Contact: Azza Ismail, Dr.
• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85251
      • Recruiting
      • HonorHealth Research Institute - Bob Bove Neuroscience Institute
      • Contact: Todd Levine, Dr.
  • Florida
    • Altamonte Springs, Florida, United States, 32714
      • Recruiting
      • Neuro of Central Florida
      • Contact: Alicia Cabrera, Dr.
    • Coral Springs, Florida, United States, 33067
      • Recruiting
      • Healthcare Innovations
      • Contact: Sonia Kalirao, Dr.
    • Miami, Florida, United States, 33122
      • Recruiting
      • Premier Clinical Research
      • Contact: Diego Rielo, Dr.
    • Miami, Florida, United States, 33032
      • Recruiting
      • Homestead Associates
      • Contact: Angel Carrasco, Dr.
  • Kentucky
    • Nicholasville, Kentucky, United States, 40356
      • Recruiting
      • Baptist Health Lexington
      • Contact: James Winkley, Dr.
  • Massachusetts
    • Boston, Massachusetts, United States, 02131
      • Recruiting
      • Boston Clinical Trials
      • Contact: Deborah Green-LaRoche, Dr.

Participation Criteria

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

How is the study designed?

Design Details

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

Number of Arms

2

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	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	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	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	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	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	To evaluate safety and tolerability by assessment of occurrence of Adverse Events.	72 weeks

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Estimated): October 1, 2024
• Study Completion (Estimated): October 1, 2032

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): April 18, 2024
• Last Update Submitted That Met QC Criteria: April 17, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• 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