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

Study Overview
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Brief Summary
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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
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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

Official Title
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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)

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: IMU-838 tablets
* Drug: Placebo matching IMU-838 tablets


Participation Criteria
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Eligibility Criteria
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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: At least 2 relapses in the last 24 months before randomization, or At least 1 relapse in the last 12 months before randomization, or 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: IMU-838<br>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<br>* Patients are randomized to IMU-838 or placebo in ratio 1:1<br>* Other names: vidofludimus calcium;|
| Placebo Comparator: Placebo<br>Matching placebo, as described for the test product, identical number of tablets as given for IMU-838. | Drug: Placebo matching IMU-838 tablets<br>* Patients are randomized to IMU-838 or placebo in ratio 1:1<br>* Other names: Placebo matching vidofludimus calcium;|

What is the study measuring?
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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 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 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 |