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

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: Recruiting
• Conditions: Multiple Sclerosis
• 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: Up to 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

• Albania
  • Tirana, Albania, 1005
    • Recruiting
    • Klinika Mjekesore Nuova, Neurology Clinic
    • Contact: Hajri Gerbi, Dr.
  • Tirana, Albania
    • Recruiting
    • Hygeia Hospital Tirana
    • Contact: Erion Dushi, Dr.
• Bulgaria
  • Blagoevgrad, Bulgaria, 2700
    • Recruiting
    • MHAT Puls AD
    • Contact: Sasho Kastrev, Dr.
  • Burgas, Bulgaria, 8000
    • Recruiting
    • MHAT "Heart and Brain", EAD
    • Contact: Ivan Dimitrov, Prof.
  • Pleven, Bulgaria, 5800
    • Recruiting
    • MC Exacta Medica OOD
    • Contact: Albena Antimova, Dr.
  • Pleven, Bulgaria, 5800
    • Recruiting
    • MHAT Avis Medica
    • Contact: Hristo Lilovski, Dr.
  • Pleven, Bulgaria, 5800
    • Recruiting
    • UMHAT Dr.Georgi Stranski EAD
    • Contact: Maya Danovska, Dr.
  • Pleven, Bulgaria
    • Recruiting
    • Heart and Brain University Hospital
    • Contact: Plamen Bozhinov, Dr.
  • Pleven, Bulgaria
    • Recruiting
    • MC Vita 1
    • Contact: Plamen Petkov, Dr.
  • Plovdiv, Bulgaria, 4002
    • Recruiting
    • UMHAT Sveti Georgi
    • Contact: Georgi Slavov, Prof.
  • Ruse, Bulgaria
    • Recruiting
    • UMHAT "Medica Ruse"
    • Contact: Rositsa Krasteva, Dr.
  • Sofia, Bulgaria, 1431
    • Recruiting
    • UMHAT "Alexandrovska" EAD
    • Contact: Ivaylo Tarnev, Prof.
  • Sofia, Bulgaria, 1000
    • Recruiting
    • CCB Medical Institute Ministry of Interior
    • Contact: Kosta Kostov, Dr.
  • Sofia, Bulgaria, 1000
    • Recruiting
    • Diagnostic and Consultative Center Neoclinic
    • Contact: Rosen Ikonomov, Dr.
  • Sofia, Bulgaria, 1606
    • Recruiting
    • Military Medical Academy MHAT
    • Contact: Radostina Dimova, Dr.
  • Sofia, Bulgaria
    • Recruiting
    • Military Medical Academy
    • Contact: Stratieva Stratina, Dr.
  • Sofia, Bulgaria
    • Recruiting
    • UMHATEM N.Pirogov
    • Contact: Maria Dimitrova, Dr.
  • Sofia, Bulgaria, 1000
    • Recruiting
    • UMHAT "Sveti Ivan Rilski" EAD
    • Contact: Penko Shotekov, Prof.
  • Sofia, Bulgaria, 1113
    • Recruiting
    • MHATNP "Sveti Naum", EAD
    • Contact: Ivan Milanov, Prof.
  • Sofia, Bulgaria, 1113
    • Recruiting
    • MHATNPsy Sveti Naum EAD
    • Contact: Paraskeva Stamenova, Prof.
  • Sofia, Bulgaria, 1431
    • Recruiting
    • UMHAT "Alexandrovska"
    • Contact: Latchezar Traykov, Prof.
  • Sofia, Bulgaria, 1618
    • Recruiting
    • MHAT "Sveta Sofia" EOOD
    • Contact: Emil Olevski, Dr.
  • Sofia, Bulgaria
    • Recruiting
    • UMHAT"Tsaritsa Yoanna -ISUL
    • Contact: Evgenia Vasileva-Ruscheva, MD
  • Varna, Bulgaria
    • Recruiting
    • UMHAT "Sveta Marina" EAD, First Clinic of Neurological Diseases
    • Contact: Ara Kaprelyan, MD
• Colombia
  • Bogotá, Colombia
    • Recruiting
    • Clínica Colsanitas S.A. Sede Clínica Universitaria Colombia
    • Contact: Carlos Navas, MD
  • Puerto Colombia, Colombia
    • Recruiting
    • Neurocountry Portoazul S.A.S.
    • Contact: Laureano Caparroso Diaz, MD
• Georgia
  • Tbilisi, Georgia
    • Recruiting
    • Eristavi Experimental Center
    • Contact: Natia Zarkua, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • J.S.C. Curatio Clinic
    • Contact: Anna Gauarashvili, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • Katsiashvili Emergency Center
    • Contact: Darejan Gugutsidze, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • Khechinashvili University Hospital
    • Contact: Marina Janelidze, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • LTD Aversi Clinic
    • Contact: Maka Mania, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • MediClub Georgia LLC
    • Contact: Nana Guldedava, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • Pineo Medical Ecosystem LTD
    • Contact: Alexander Tsiskaridze, Dr.
  • Tbilisi, Georgia
    • Recruiting
    • Sarajishvili Neurology Institute
    • Contact: Roman Shakarishvili, Dr.
  • Tbilisi, Georgia, 0141
    • Recruiting
    • 1st Uni Clinic of Tbilisi LEPL
    • Contact: Maia Beridze, Prof.
  • Tbilisi, Georgia
    • Recruiting
    • Ltd New Hospitals
    • Contact: Temur Marghania, Dr.
• Greece
  • Athens, Greece
    • Recruiting
    • Athens Medical Center
    • Contact: Klimentini Karageorgiou, Prof.
  • Thessaloníki, Greece
    • Recruiting
    • Thessaloniki Hosptl
    • Contact: Dimitrios Kazis, Prof.
• India
  • Gandhinagar, India, 382428
    • Recruiting
    • Kanoria Hospital & Research Centre
    • Contact: Devasi Visana, Dr.
  • Mangalore, India, 575002
    • Recruiting
    • Mallikatte, Kadri
    • Contact: Shankara Nellikunja, Dr.
  • Nagpur, India
    • Recruiting
    • Jasleen Hospital
    • Contact: Sanjay Ramteke, Dr.
  • New Delhi, India, 110060
    • Recruiting
    • Sir Ganga Ram Hospital
    • Contact: Laxmikant R. Singh Tomar, Dr.
  • Pune, India, 411001
    • Recruiting
    • Ruby Hospital
    • Contact: Santosh Sontakke, Dr.
  • Shimla, India, 171001
    • Recruiting
    • Indira Gandhi Medical College & Hospital
    • Contact: Sudhir Sharma, Dr.
  • Varanasi, India, 221005
    • Recruiting
    • Institute of Medical Sciences Banaras Hindu University,IMS BHU Varanasi
    • Contact: Abhishek Phatakh, Dr.
• Jordan
  • Amman, Jordan
    • Recruiting
    • TSH Advanced Clinical Center
    • Contact: Murad Rasheed, Dr.
  • Irbid, Jordan
    • Recruiting
    • Irbid Speciality Hospital
    • Contact: Eyad Awad, Dr.
• Lebanon
  • Beirut, Lebanon
    • Recruiting
    • Hotel Dieu de France Hospital
    • Contact: Halim Abboud, Dr.
  • Hamra, Lebanon, 1107-2020
    • Recruiting
    • AUB Medical Center
    • Contact: Samia Khoury, Dr.
• Lithuania
  • Kaunas, Lithuania, 50161
    • Recruiting
    • Lietuvos Sveikatos Mokslu Universitetas - Kauno Klinikos
    • Contact: Renata Balnyte, Dr.
  • Klaipėda, Lithuania, 92288
    • Recruiting
    • Klaipedos Universitetine Ligonine - Klaipedos Issetines Sklerozes Centra
    • Contact: Lina Malciene, Dr.
• Mexico
  • Culiacán, Mexico, 80020
    • Recruiting
    • Neurociencias Estudios Clínicos S.C
    • Contact: Elmer G. Lopez Meza, Dr.
  • Guadalajara, Mexico, 44670
    • Recruiting
    • Instituto Jalisciense de Metabolismo, SC
    • Contact: Jose L. Ruiz Sandoval, Dr.
  • Mexico City, Mexico, 06700
    • Recruiting
    • Cliditer S.A de C.V
    • Contact: Minerva Lopez Ruiz
  • Mexico City, Mexico, 14050
    • Recruiting
    • Unidad de Investigacion en Salud de Chihuahua S.C.
    • Contact: Alma Vigueras, Dr.
  • Mexico City, Mexico, 03310
    • Recruiting
    • Grupo Medico Camino Sc
    • Contact: Freddy Castro Farfan, Dr.
  • Mexico City, Mexico
    • Recruiting
    • Clinstile SA de CV
    • Contact: Sandra Quiñones Aguilar, Dr.
  • Morelia, Mexico, 58000
    • Recruiting
    • Centro de Morelia
    • Contact: Guillermo Punzo-Bravo, Dr.
  • Veracruz, Mexico, 91900
    • Recruiting
    • Sociedad de Metabolismo y Corazon, S.C.
    • Contact: Marco Santos Diaz, Dr.
  • Veracruz, Mexico, 91900
    • Recruiting
    • Faicic de RL de CV
    • Contact: David Reyes Barrios, Dr.
• Moldova, Republic of
  • Chisinau, Moldova, Republic of
    • Recruiting
    • Instititute of Emergency Medicine
    • Contact: Stanislav Groppa, Dr.
  • Chisinau, Moldova, Republic of
    • Recruiting
    • Medico-Sanitary Public Institution, Institute of Neurology and Neurosurgery "Diomid Gherman"
    • Contact: Olesea Odainic, Dr.
  • Chisinau, Moldova, Republic of
    • Recruiting
    • The Diomid Gherman Institute of Neurology and Neurosurgery
    • Contact: Mihail Gavriliuc, Dr.
• Montenegro
  • Nikšić, Montenegro
    • Recruiting
    • General Hospital Niksic
    • Contact: Zlatana Perovic, MD
  • Podgorica, Montenegro
    • Recruiting
    • Clinical Center of Montenegro
    • Contact: Ljijana Radulovic, MD
• North Macedonia
  • Skopje, North Macedonia
    • Recruiting
    • Hospital "8 mi Septemvri"
    • Contact: Tatjana Stoshevska Deleva, Dr.
  • Skopje, North Macedonia
    • Recruiting
    • University Clinic of Neurology
    • Contact: Ivan Barbov, Dr.
• Spain
  • Madrid, Spain
    • Recruiting
    • Hospital Universitario La Paz
    • Contact: Antonio Tallon, Dr.
• Ukraine
  • Chernivtsi, Ukraine
    • Recruiting
    • Chernihiv Regional Hospital
    • Contact: Valeriy Pashkovskyy, MD
  • Ivano-Frankivs'k, Ukraine, 76493
    • Active, not recruiting
    • Neuro Global, LLC
  • Ivano-Frankivs'k, Ukraine, 76008
    • Recruiting
    • Regional Clinical Hospital
    • Contact: Galyna Chmyr, Dr.
  • Khmelnytskyi, Ukraine
    • Recruiting
    • Khmelnytsky regional hospital of war veterans
    • Contact: Inna Kovalchuk, MD
  • Kiev, Ukraine
    • Recruiting
    • Clinical Hospital #15 of the Podilskyi District of the Kyiv City
    • Contact: Olga Kovalenko, MD
  • Kiew, Ukraine
    • Recruiting
    • Kyiv City Hospital 4
    • Contact: Tetiana Kobys, MD
  • Kyiv, Ukraine, 3037
    • Active, not recruiting
    • "Medbud"
  • Kyiv, Ukraine, 4212
    • Active, not recruiting
    • SMART medical center
  • Odesa, Ukraine
    • Recruiting
    • Odesa Regional Clinical Hospital, Department of Neurosurgery
    • Contact: Alla Goloborodko, MD
  • Poltava, Ukraine
    • Recruiting
    • Medical and diagnostic center of a LLC "Medcontinent", neurology and rehabilitation center
    • Contact: Nataliya Lytvynenko, MD
  • Ternopil', Ukraine, 46027
    • Recruiting
    • Ternopil Psycho-Neuro Hospital
    • Contact: Svitlana Skhrobot, Dr.
  • Uzhhorod, Ukraine
    • Recruiting
    • Regional Clinical Center for Neurosurgery and Neurology
    • Contact: Volodymyr Smolanka, MD
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85004
      • Recruiting
      • Xenoscience, Inc., 21st Century Neurology
      • Contact: Stephen Flitman, Dr.
  • Florida
    • Bradenton, Florida, United States, 34205
      • Recruiting
      • Bradenton Research Center
      • Contact: Eric Martin Folkens, Dr.
    • Miami, Florida, United States, 33165
      • Withdrawn
      • Reliant Medical Research, LLC
    • Naples, Florida, United States, 34105
      • Recruiting
      • Collier Neurologic Specialists
      • Contact: Matthew Baker, Dr.
    • Ormond Beach, Florida, United States, 32174
      • Recruiting
      • Neurology Associates of Ormond Beach
      • Contact: James Scott, Dr.
  • Illinois
    • Northbrook, Illinois, United States, 60062
      • Recruiting
      • Consultants in Neurology, Ltd
      • Contact: Daniel Wynn, Dr.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 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

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 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.	72 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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
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 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
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.	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): November 18, 2021
• Primary Completion (Estimated): September 1, 2024
• Study Completion (Estimated): September 1, 2032

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): 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; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium; Calcium, Dietary
• 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