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

Phase 3

Recruiting

• Conditions: Multiple Sclerosis, Relapsing-Remitting
• Interventions: Drug: IMU-838 tablets; Drug: Placebo matching IMU-838 tablets

• Registration Number: NCT05201638
• Lead Sponsor: Immunic AG

Brief 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)

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 Timeline

• Study First Submitted: 2021-12-13
• Study Start: 2022-01-12
• Study First Submitted QC: 2022-01-20
• Study First Posted: 2022-01-21
• Status Verified: 2024-04
• Last Update Submitted: 2024-04-17
• Last Update Posted: 2024-04-18
• Primary Completion: 2024-10
• Study Completion: 2032-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 1050

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.

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IMU-838	IMU-838 tablets	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.
Placebo	Placebo matching IMU-838 tablets	Matching placebo, as described for the test product, identical number of tablets as given for IMU-838.

Primary Outcome Measures

Name	Time	Method
To evaluate efficacy of IMU-838 versus placebo based on time to first relapse	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.

Secondary Outcome Measures

Name	Time	Method
Effect of IMU-838 versus placebo on volume of new T2 lesions	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.
Effect of IMU-838 versus placebo on disability progression	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.
Effect of IMU-838 versus placebo on whole brain atrophy	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.
Effect of IMU-838 versus placebo on cognitive performance	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.
Safety of IMU-838 versus placebo	72 weeks	To evaluate safety and tolerability by assessment of occurrence of Adverse Events.

Trial Locations

Locations (90)

T.C. Ministry of Health Kutahya Provincial Directorate of Health Kutahya University of Health Sciences Evliya Celebi Training and Research Hospital; 🇹🇷 Kütahya, Turkey

Centrum Med. Ibismed; 🇵🇱 Zabrze, Poland

Vojnomedicinska akademija; 🇷🇸 Belgrade, Serbia

Univerzitetski Klinicki centar Nis; 🇷🇸 Niš, Serbia

Ukrainian State Research Institute of Medico-Social Problems of Disability; 🇺🇦 Dnipro, Ukraine

Dopomoga Plus medical center; 🇺🇦 Kyiv, Ukraine

Homestead Associates; 🇺🇸 Miami, Florida, United States

Premier Clinical Research; 🇺🇸 Miami, Florida, United States

Boston Clinical Trials; 🇺🇸 Boston, Massachusetts, United States

HonorHealth Research Institute - Bob Bove Neuroscience Institute; 🇺🇸 Scottsdale, Arizona, United States

Healthcare Innovations; 🇺🇸 Coral Springs, Florida, United States

Neuro of Central Florida; 🇺🇸 Altamonte Springs, Florida, United States

Baptist Health Lexington; 🇺🇸 Nicholasville, Kentucky, United States

Heratsi Hospital Complex 1; 🇦🇲 Yerevan, Armenia

Erebouni Medical Center; 🇦🇲 Yerevan, Armenia

UCC of Rep of Srpska; 🇧🇦 Banja Luka, Bosnia and Herzegovina

Cantonal Hospital Bihac Dr. Irfan Ljubijankic; 🇧🇦 Bihać, Bosnia and Herzegovina

University Clinical Center of Sarajevo; 🇧🇦 Sarajevo, Bosnia and Herzegovina

University Clinical Center Sarajevo; 🇧🇦 Sarajevo, Bosnia and Herzegovina

University Clinical Center Tuzla; 🇧🇦 Tuzla, Bosnia and Herzegovina

Astra Clinic; 🇪🇪 Tallinn, Estonia

Post-Graduation Institute of Medical Education and Research (PGIMER); 🇮🇳 Chandigarh, India

All India Institute of Medical Sciences; 🇮🇳 New Delhi, India

Dr Ram Manohar Lohia Institute of Medical Sciences; 🇮🇳 Lucknow, India

Fortis Memorial Research Institute; 🇮🇳 Gurugramam, India

GB Pant Institute of Postgraduate Medical Education and Research; 🇮🇳 New Delhi, India

SRI Guru Ram Das Institute of Medical Sciences and Research; 🇮🇳 Punjabi Bagh, India

DKS PGI; 🇮🇳 Raipur, India

Centro de Investig. Médicas; 🇵🇪 Lima, Peru

NZOZ Wielospecjalistyczna Poradnia Lekarska "Synapsis"; 🇵🇱 Katowice, Poland

NZOZ Neuromed; 🇵🇱 Lublin, Poland

Indywidualna Praktyka Lekarska prof. Konrad Rejdak; 🇵🇱 Lublin, Poland

NZOZ Hertmanowskiej; 🇵🇱 Plewiska, Poland

Neuro-Medic Janusz Zbrojkiewicz; 🇵🇱 Katowice, Poland

Instytut Zdrowia Boczarska; 🇵🇱 Oświęcim, Poland

Centrum Medyczne NeuroProtect; 🇵🇱 Warsaw, Poland

NZOZ Neuro-Kard; 🇵🇱 Poznań, Poland

FutureMeds Warszawa Centrum; 🇵🇱 Warsaw, Poland

SC Sana Monitoring SRL; 🇷🇴 Bucharest, Romania

Elias University Emergency Hospital; 🇷🇴 Bucharest, Romania

Asociatia Comunitatea Oamenilor; 🇷🇴 Craiova, Romania

Spitalul clinic CF Constanta; 🇷🇴 Constanţa, Romania

Clubul Sanatatii SRL; 🇷🇴 Câmpulung, Romania

Aria Clinic SRL; 🇷🇴 Sibiu, Romania

Neuro Therapy; 🇷🇴 Timişoara, Romania

Spit Jud Branzeu TIM Neuro; 🇷🇴 Timişoara, Romania

Klinicko bolnicki centar Zvezdara; 🇷🇸 Belgrade, Serbia

Klinicko bolnicki centar Dr Dragisa Misovic - Dedinje; 🇷🇸 Belgrade, Serbia

Opsta bolnica Medicinski sistem Beograd; 🇷🇸 Belgrade, Serbia

Univerzitetski Klinicki centar Kragujevac; 🇷🇸 Kragujevac, Serbia

Adana Baskent Hospital; 🇹🇷 Adana, Turkey

Baskent University Ankara Hospital; 🇹🇷 Ankara, Turkey

Hsptl Sveti Vracevi; 🇷🇸 Novi Kneževac, Serbia

Opsta bolnica Djordje Jovanovic Zrenjanin; 🇷🇸 Zrenjanin, Serbia

Acibadem Adana Hospital; 🇹🇷 Adana, Turkey

General Hospital Uzice; 🇷🇸 Užice, Serbia

Klinicko Bolnicki centar Zemun; 🇷🇸 Zemun, Serbia

T.C. Ministry of Health Istanbul Haseki Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Bezmialem Vakif University Hospital; 🇹🇷 Istanbul, Turkey

Sancaktepe Sehit Prof.Dr. Ilhan Varank Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Haydar Pasa Num. EAH; 🇹🇷 Istanbul, Turkey

Manisa Celal Bayar University Hafsa Sultan Hospital; 🇹🇷 Manisa, Turkey

Marmara University Pendik Training and Research Hospital; 🇹🇷 Istanbul, Turkey

Kocaeli University Research and Application Hospital; 🇹🇷 Kocaeli, Turkey

19 Mayis University Medical Faculty Hospital Health Application and Research Center; 🇹🇷 Samsun, Turkey

Communal noncommercial enterprise "First Cherkasy City Hospital"; 🇺🇦 Cherkasy, Ukraine

Namik Kemal Uni Hospital; 🇹🇷 Tekirdağ, Turkey

Zonguldak Bulent Ecevit University Health Practice and Research Hospital; 🇹🇷 Zonguldak, Turkey

MS Diagnosis Treatment Center; 🇺🇦 Cherkasy, Ukraine

Dnipro City Hospital 6; 🇺🇦 Dnipro, Ukraine

Chernihiv City Hospital 4; 🇺🇦 Chernihiv, Ukraine

Municipal Institution "Dnipropetrovsk Regional Rehabilitation Hospital" of Dnipropetrovsk Regional Council"; 🇺🇦 Dnipro, Ukraine

"University Clinic" of Dnipro State Medical University, Department of Neurology; 🇺🇦 Dnipro, Ukraine

Communal Non-Commercial Medical Enterprise "O.T.Bohayevskyi Kremenchuk City Hospital #1; 🇺🇦 Kremenchuk, Ukraine

1 Private Clinic Medical Center; 🇺🇦 Kyiv, Ukraine

State Institution "National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine; 🇺🇦 Kyiv, Ukraine

Volyn Reg Clin Hospital; 🇺🇦 Luts'k, Ukraine

Lviv Regional Central Hospital; 🇺🇦 Lviv, Ukraine

City Clinical Hospital 2; 🇺🇦 Rivne, Ukraine

5 City Clin Hospital; 🇺🇦 Lviv, Ukraine

Communal institution "City Clinical Hospital №3" of Poltava City Council; 🇺🇦 Poltava, Ukraine

Sumy Reg Clinical Hospital; 🇺🇦 Sumy, Ukraine

LCC Medical center INET-09; 🇺🇦 Zaporizhzhya, Ukraine

Salutem; 🇺🇦 Vinnytsia, Ukraine

Zaporizhia Med; 🇺🇦 Zaporizhzhya, Ukraine

Zaporizhia Regional Clinic Hospital; 🇺🇦 Zaporizhzhya, Ukraine

Zaporizhzhya Hospital 9; 🇺🇦 Zaporizhzhya, Ukraine

Zaporizhzhya City Hospital 6; 🇺🇦 Zaporizhzhya, Ukraine

Royal Devon Uni NHS; 🇬🇧 Exeter, United Kingdom

Royal Hallamshire Hospital; 🇬🇧 Sheffield, United Kingdom