Clinical trial NCT03846219: MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS)
Official title: Randomized, Double-blind, Placebo-controlled, Multicenter Phase 2 Trial Assessing the Effect of IMU-838 on Disease Activity, as Measured by Magnetic Resonance Imaging (MRI), as Well as Safety and Tolerability in Patients With Relapsing-remitting Multiple Sclerosis (RRMS)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Relapsing-Remitting Multiple Sclerosis (RRMS)
Keywords: RRMS
Multiple Sclerosis (MS)
Lead sponsor: Immunic AG
Sponsor class: INDUSTRY
First posted: 2019-02-19
Enrollment: 210
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a Phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 (30 mg/day and 45 mg/day) in the main study (10 mg/day for the patients in the substudy) in patients with RRMS and evidence of active disease. The trial consists of a screening period, a blinded 24-week main treatment period, and an optional initially blinded, then open-label extended treatment period of up to 9.5 years.

The trial includes 2 patient cohorts:

* Cohort 1 main trial: main Phase 2 trial with assessment of primary and key secondary endpoints.
* Cohort 2 sub-trial: additional sub-trial with a small double-blind, placebo-controlled, randomized, parallel-group assessment of 10 mg/day IMU-838 dose to provide additional data for pharmacodynamic modelling.
Primary purpose: TREATMENT

Brief summary: This is a Phase 2 multicenter, double-blind, placebo-controlled, randomized, parallel-group trial to assess the efficacy and safety of 2 once-daily oral doses of IMU-838 (vidofludimus calcium), a small molecule inhibitor of dihydroorotate dehydrogenase (DHODH), 30 mg/day and 45 mg/day in the main study, cohort 1 (and 10 mg/day for the patients in the cohort 2 substudy), in patients with RRMS and evidence of active disease.

The trial consists of a screening period, a blinded 24-week main treatment period, and an optional initially blinded, then open-label extended treatment period of up to 9.5 years.

About 40 centers are planned to participate in Romania, Bulgaria, Ukraine, and Poland; potential additional centers in Hungary and Croatia were not used. The study started with 195 patients in the main group (cohort 1) planned to be randomized 1:1:1 to treatment with 30 mg/day or 45 mg/day IMU-838, or placebo (65 patients each) in the main treatment period. During the extended treatment period, patients were initially re-randomized so that patients previously on placebo were re-randomized 1:1 to treatment with 30 g/day or 45 mg/day IMU-838, all other patients were re-randomized to the same treatment they previously received.

With approval of Protocol Version 3.0, a sub-study patient group (cohort 2) has been added with up to 60 patients, randomized to placebo or 10 mg IMU-838 for 24 weeks after which the option is available to continue into the extended treatment period and the recommended dose of 30 mg/day. However, based on discussion between investigator and patient 45 mg/day IMU-838/day may also be used.


Eligibility criteria: Inclusion criteria for the main treatment period

1. Male or female patient (age ≥18 to 55 years, inclusive)
2. Diagnosis of RRMS according to the revised McDonald criteria (2017) Note: The diagnosis of MS (including "dissemination in time") must have been established before the patient is screened for the trial.
3. Disease activity evidenced

   * by either at least 2 relapses in the last 24 months, or at least 1 relapse in the last 12 months before randomization (relapses must have been assessed and documented by a physician in the patient files), AND
   * ≥1 documented Gd+ MS-related brain lesion, in the last 6 months before informed consent (date of MRI examination as well as copy of MRI report or representative image has to be available and accessible as patient source data at the study site)
4. Expanded Disability Status Scale (EDSS) score between 0 and 4.0 (inclusive) at Screening Visit 1
5. Female patients

   * must be of non-child-bearing potential i.e. surgically sterilized (hysterectomy, bilateral salpingectomy, bilateral oophorectomy at least 6 weeks before Screening Visit 1) or post menopausal (where postmenopausal is defined as no menses for 12 months without an alternative medical cause), or
   * if of child-bearing potential, must have a negative pregnancy test at Screening Visit 1 (blood test) and before the first IMP intake (Day 0 urine test). They must agree not to attempt to become pregnant, must not donate ova, and must use a highly effective contraceptive method (see below) together with a barrier method between trial consent and 30 days after the last intake of the of the IMP.

   Highly effective forms of birth control are those with a failure rate less than 1% per year and include:
   * oral, intravaginal, or transdermal combined (estrogen and progestogen containing) hormonal contraceptives associated with inhibition of ovulation
   * oral, injectable, or implantable progestogen-only hormonal contraceptives associated with inhibition of ovulation
   * intrauterine device or intrauterine hormone-releasing system
   * bilateral tubal occlusion
   * vasectomized partner (i.e. the patient's male partner underwent effective surgical sterilization before the female patient entered the clinical trial and is the sole sexual partner of the female patient during the clinical trial)
   * sexual abstinence (acceptable only if it is the patient's usual form of birth control/lifestyle choice; periodic abstinence \[e.g. calendar, ovulation, symptothermal, postovulation methods\] and withdrawal are no acceptable methods of contraception)

   Barrier methods of contraception include:
   * Condom
   * Occlusive cap (diaphragm or cervical/vault caps) with spermicidal gel/film/cream/suppository
6. Male patients must agree not to father a child or to donate sperm starting at Screening Visit 1, throughout the clinical trial and for 30 days after the last intake of the IMP. Male patients must also

   * abstain from sexual intercourse with a female partner (acceptable only if it is the patient's usual form of birth control/lifestyle choice), or
   * use adequate barrier contraception during treatment with the IMP and until at least 30 days after the last intake of the IMP, and
   * if they have a female partner of childbearing potential, the partner should use a highly effective contraceptive method as outlined in inclusion criterion 5
   * if they have a pregnant partner, they must use condoms while taking the IMP to avoid exposure of the fetus to the IMP
7. Willingness and ability to comply with the protocol
8. Written informed consent given prior to any trial-related procedure

Inclusion criteria for optional extended treatment period

1. Completed 24 weeks of main treatment
2. Baseline MRI and Week 24 MRI, as well as 2 additional post-dose MRIs

Continuation criteria for optional extended treatment period

1. In case the initial Week 24 MRI was not evaluated at least partially assessable, availability of a repeated Week 24 MRI
2. Week 24 MRI (initial or repeated one, if applicable) evaluated at least partially assessable

Exclusion criteria

MS-related exclusion criteria

1. Any disease other than MS that may better explain the signs and symptoms, including history of complete transverse myelitis
2. Signs and symptoms suggestive of transmissible spongiform encephalopathy, or family members who suffer(ed) from these
3. Clinical signs or presence of laboratory findings suggestive for neuromyelitis optica (NMO) spectrum disorders or MOG-associated encephalomyelitis (i.e. presence of anti-NMO \[aquaporin-4\] antibodies or anti-MOG-antibodies)
4. MS types other than RRMS
5. Any MRI finding, atypical for MS, including but not limited to a longitudinally extensive spinal cord lesion
6. Any active and uncontrolled coexisting autoimmune disease, other than MS (except for type 1 diabetes mellitus and inflammatory bowel disease)
7. An MS relapse within 30 days before Screening Visit 1 and/or during the screening period (until Day 0)

   Therapy exclusion criteria
8. Any previous or current use of the following MS treatments: monoclonal antibodies (natalizumab, alemtuzumab, daclizumab, ocrelizumab, anti-CD4, rituximab or belimumab, including their biosimilars), total lymphoid irradiation, bone marrow transplantation, stem cell transplantation, or any use of DHODH inhibitors, including teriflunomide (Aubagio™) or leflunomide (Arava™)
9. Any use of the following MS treatments within 12 months before the date of informed consent: any cytokine (other than interferon) or anti-cytokine therapy, intravenous immunoglobulin, mitoxantrone, cytotoxic or immunosuppressive therapy (including, but not limited to azathioprine and cyclophosphamide, excluding only systemic corticosteroids or adrenocorticotrophic hormone \[ACTH\]), tofacitinib, methotrexate, mycophenolate mofetil, mycophenolate sodium, fingolimod, any calcineurin inhibitors (e.g. tacrolimus, cyclosporine, or pimecrolimus)
10. Any use of the following MS treatments within 30 days before the date of informed consent: interferon-β, glatiramer acetate, dimethyl fumarate and plasmapheresis
11. Within 30 days before the baseline MRI: Use of systemic corticosteroids (intravenous or oral) or ACTH
12. Use of the following concomitant medications is prohibited at Screening Visit 1 and throughout the duration of the trial:

    * any medication known to significantly increase urinary elimination of uric acid, in particular lesinurad (Zurampic™) as well as uricosuric drugs such as probenecid
    * treatments for any malignancy, in particular irinotecan, paclitaxel, tretinoin, bosutinib, sorafinib, enasidenib, erlotinib, regorafenib, pazopanib and nilotinib
    * any drug significantly restricting water diuresis, in particular vasopressin and vasopressin analogs
    * use of rosuvastatin at daily doses higher than 10 mg
13. Use of any investigational product within 8 weeks or 5 x the respective half-life before the date of informed consent, whichever is longer, and throughout the duration of the trial

    Immune response exclusion criteria
14. Conditions negatively affecting the immune response such as previous organ transplant
15. Clinically significantly low lymphocyte and/or neutrophil count (Common Terminology Criteria for AEs Grade of 2 or higher), i.e.

    * lymphocyte count \<800/mm³ (0.8 x 109/L), and/or
    * neutrophil count \<1,500/mm³ (1.5 x 109/L)
16. History of chronic systemic infections within 6 months before the date of informed consent, including but not limited to tuberculosis, human immunodeficiency virus (HIV), hepatitis B or C
17. Positive IFNγ release assay for Mycobacterium tuberculosis at Screening Visit 1
18. Positive hepatitis B virus surface antigen (HBsAg), hepatitis B core antibody (HBcAb), positive HCV-antibody (HCV-Ab) and/or HIV-antigen-antibody test at Screening Visit 1
19. Any live vaccinations within 30 days before the date of informed consent except for the influenza vaccine Other medical history and concomitant disease exclusion criteria
20. Presence of the following laboratory values at Screening Visit 1:

    * platelet count \<100,000/mm³ (\<100 109/L)
    * serum creatinine \>1.5 x ULN
    * total bilirubin, ALT, or GGT \>1.5 x ULN
    * Serum uric acid levels at Screening Visit 1 \>1.2 x ULN (for women \>6.8 mg/dL, for men \>8.4 mg/dL)
    * indirect (unconjugated) bilirubin \>1.2 x ULN (i.e. \>1.1 mg/dL)
21. Known history of nephrolithiasis or underlying condition with a strong association of nephrolithiasis, including hereditary hyperoxaluria or hereditary hyperuricemia
22. History or clinical diagnosis of gout
23. Renal impairment defined as estimated glomerular filtration rate ≤60 mL/min/1.73m²
24. Known or suspected Gilbert syndrome
25. Diagnosis or suspected liver function impairment which may cause fluctuating liver function tests during this trial, as assessed by the investigator
26. History or presence of serious or acute heart disease such as uncontrolled cardiac dysrhythmia or arrhythmia, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure (New York Heart Association \[NYHA\] class 3 or 4) Note: NYHA class 3: Cardiac disease resulting in marked limitation of physical activity. Patients are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea, or anginal pain. NYHA class 4: Cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present even at rest. If any physical activity is undertaken, discomfort is increased.
27. Clinically relevant, severe pulmonary diseases, uncontrolled hypertension, or poorly controlled diabetes
28. Concurrent malignancy or prior malignancy within the previous 10 years except for the following: adequately-treated non-melanoma skin cancer and adequately-treated cervical cancer
29. History or presence of any major medical or psychiatric illness (such as severe depression, psychosis, bipolar disorder), history of suicide attempt, or current suicidal ideation that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol
30. Epilepsy or seizures not adequately controlled by treatment
31. Any other substantial medical condition that in the opinion of the investigator could create undue risk to the patient or could affect adherence with the trial protocol

    General exclusion criteria
32. Current or past (within 12 months of Screening Visit 1) alcohol or drug abuse
33. Any condition that would prevent the patient from undergoing an MRI scan, including:

    * claustrophobic conditions
    * unable to receive Gd-based MRI-contrast agents due to history of hypersensitivity to Gd based contrast agents, or severe renal insufficiency
    * presence of metallic implants incompatible with brain MRI
34. Legal incapacity, limited legal capacity, or any other condition that makes the patient unable to understand the patient information and informed consent form
35. Pregnant or breastfeeding
36. An employee of an investigator or sponsor or an immediate relative of an investigator
37. Patients institutionalized due to judicial or administrative order

Exclusion criteria for optional extended treatment period

1. Any ongoing, clinically significant (as assessed by the investigator) treatment-emergent (started after intake of IMP) AE or laboratory abnormality (including blood chemistry and urinalysis)
2. Significant treatment or trial non-compliance during the main treatment period (as assessed by the investigator), and/or inability or unwillingness to follow instructions by trial personnel
3. Treatment compliance \<70% during the main treatment period
4. Significant protocol deviations during the main treatment period that are assessed by the investigator to negatively affect further patient cooperation in this trial

Primary outcomes:
measure: Difference Between 45 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
timeFrame: Up to Week 24
Secondary outcomes:
measure: Difference Between 30 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
timeFrame: Up to Week 24
measure: Difference Between 45 mg/Day IMU-838 and 30 mg/Day IMU-838 in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
timeFrame: At Week 24
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Mean Number of CUA Lesions Per Patient Per Scan at Weeks 6, 12, 18 and 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Cumulative Number of CUA MRI Lesions up to Weeks 6, 12, and 18
timeFrame: Throughout the main treatment period (Day 0 - Week 18)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Volume Changes of T2 Lesions at Weeks 6, 12, 18 and 24 Compared to Baseline
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the T2-lesion Load at Weeks 6, 12, 18 and 24 Compared to Baseline
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the T1-lesion Load at Weeks 6, 12, 18 and 24 Compared to Baseline
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Cumulative Number of New Gd+ Lesions up to Weeks 6, 12, 18 and 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Cumulative Number of New T2 Lesions up to Weeks 6, 12, 18 and 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Cumulative Number of New T1 Lesions up to Weeks 6, 12, 18 and 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Number of Patients Without New Gd+ Lesions Over 24 Weeks
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Number of Patients Without New or Enlarging T2-weighted Lesions Over 24 Weeks
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Number of Patients With CUA Lesions at Week 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Number of Patients With Gd+ Lesions at Week 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for the Number of Patients With T2 Lesions at Week 24
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Differences Between Individual Treatments and Between the Pooled 30 mg/Day and 45 mg/Day Groups and Placebo in the Relapse-related Clinical Endpoints: Mean Annualized Relapse Rate (During Main and Extended Treatment Period)
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Differences Between Individual Treatments and Between the Pooled 30 mg/Day and 45 mg/Day Groups and Placebo in the Relapse-related Clinical Endpoints: Proportion of Relapse-free Patients up to Week 24 and at Extended Periods Thereafter
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Differences Between Individual Treatments and Between the Pooled 30 mg/Day and 45 mg/Day Groups and Placebo in the Relapse-related Clinical Endpoints: Time to Relapse at Time of Final Analysis of Main Part
timeFrame: Throughout the main treatment period (Day 0 - Week 24)
measure: Differences Between Treatments in Changes of Disease Activity as Measured by the Mean Change in the Expanded Disability Status Scale (EDSS) as Compared to Baseline During the Main and Extended Period (Every 12 Weeks Starting at Week 12)
timeFrame: Baseline, Week 12, and Week 24
measure: Differences Between Treatments in Changes of Disease Activity as Measured by the Number of Patients With EDSS Progression During the Main and Extended Period (Every 12 Weeks Starting at Week 12, and Cumulatively)
timeFrame: Week 12 and Week 24
measure: Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels
timeFrame: At Week 24
measure: Number of Participants With AEs
timeFrame: Up to 24 weeks
measure: Number of Participants With Serious AEs
timeFrame: Up to 24 weeks
measure: Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator)
timeFrame: Up to 24 weeks
measure: Number of Participants With AEs of Special Interest: Red Blood Cell Urine Positive, at Least of Moderate Intensity
timeFrame: Up to 24 weeks
measure: Number of Participants With AEs of Special Interest: Hematuria
timeFrame: Up to 24 weeks
measure: Number of Participants With AEs of Special Interest: Retroperitoneal Colicky Pain With Suspected or Confirmed Nephrolithiasis
timeFrame: Up to 24 weeks
measure: Number of Patients Treated With 30 mg/Day or 45 mg/Day IMU-838 as Compared to Placebo Who Experienced at Least One of the Following AEs:
timeFrame: Up to 24 weeks
measure: 12-lead Electrocardiogram (ECG): Heart Rate
timeFrame: Up to 24 weeks
measure: 12-lead Electrocardiogram (ECG): PQ-interval
timeFrame: Up to 24 weeks
measure: 12-lead Electrocardiogram (ECG): QRS-interval
timeFrame: Up to 24 weeks
measure: 12-lead Electrocardiogram (ECG): QT-interval
timeFrame: Up to 24 weeks
measure: 12-lead Electrocardiogram (ECG): Heart Rate-corrected QTc Interval (According to Bazett's Formula)
timeFrame: Up to 24 weeks
measure: Physical Examination
timeFrame: Up to 24 weeks
measure: Vital Signs: Height
timeFrame: at Screening
measure: Vital Signs: Weight (Absolute Change From Baseline at Week 24)
timeFrame: Baseline and 24 weeks
measure: Vital Signs: Body Temperature (ºC) (Absolute Change From Baseline at Week 24)
timeFrame: Baseline and 24 weeks
measure: Vital Signs: Respiratory Rate (Absolute Change From Baseline at Week 24)
timeFrame: Baseline and 24 weeks
measure: Vital Signs: Pulse Rates (Absolute Change From Baseline at Week 24)
timeFrame: Baseline and 24 weeks
measure: Vital Signs: Systolic and Diastolic Blood Pressures (Absolute Change From Baseline at Week 24)
timeFrame: Baseline and 24 weeks
measure: Micro Ribonucleic Acid (miR)-122 Expression
timeFrame: Change from Baseline to 4 hours after first dose
measure: Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine
timeFrame: At Screening Visit 1, at Week 24, and at EoS visit (EoS visit 30 days (+14 days) after last IMP intake)
measure: Time to Treatment Discontinuation for Any Reason
timeFrame: Up to 24 weeks
measure: Rate of Treatment Discontinuations up to Week 24
timeFrame: at Week 24
measure: Population Pharmacokinetics: Minimum IMU-838 Plasma Concentration Over the Dosing Interval (Cmin)
timeFrame: At Week 6 (3-10 hours post-dose)
measure: Population Pharmacokinetics: Maximum IMU-838 Plasma Concentration Over the Dosing Interval (Cmax)
timeFrame: At Week 6 (3-10 hours post-dose)
measure: Population Pharmacokinetics: Area Under the IMU-838 Plasma Concentration-time Curve Over the Dosing Interval (AUC0-τ)
timeFrame: At Week 6 (3-10 hours post-dose)
measure: Population Pharmacokinetics: IMU-838 Apparent Clearance Following Oral Dosing (CL/F)
timeFrame: At Week 6 (3-10 hours post-dose)
measure: Population Pharmacokinetics: IMU-838 Apparent Volume of Distribution (V/F)
timeFrame: At Week 6 (3-10 hours post-dose)
measure: Plasma Trough Levels of IMU-838
timeFrame: At Day 7 and Weeks 6, 12, 18, and 24
measure: Changes From Baseline in Th1 Lymphocyte Subset as Measured by Flow Cytometry
timeFrame: At Weeks 6 and 24 (in selected Biomarker Centers only)
measure: Changes From Baseline in Th17 Lymphocyte Subset as Measured by Flow Cytometry
timeFrame: At Weeks 6 and 24 (in selected Biomarker Centers only)
measure: Changes From Baseline in Treg Lymphocyte Subset as Measured by Flow Cytometry
timeFrame: At Weeks 6 and 24 (in selected Biomarker Centers only)
measure: Changes From Baseline in Serum Neurofilament
timeFrame: At Week 6 and Week 24
measure: Treatment Satisfaction Questionnaire for Medication (TSQM)
timeFrame: assessed at 6 weeks, 24 weeks, and end of study visit (EoS visit 30 days [+14 days] after last IMP intake), reported at Week 6 and Week 24
measure: Difference Between 30 mg/Day IMU-838 and Placebo, 45 mg/Day IMU-838 and Placebo, and 30 mg/Day and 45 mg/Day IMU-838 for Brain Atrophy.
timeFrame: Baseline, Week 6, Week 12, Week 18, and Week 24
Other outcomes:
Locations:
city: Blagoevgrad
country: Bulgaria
facility: MHAT Pulse AD, Department of Neurology Diseases
city: Pleven
country: Bulgaria
facility: UMHAT "Dr.Georgi Stranski" EAD Pleven Department of Professional Diseases
city: Pleven
country: Bulgaria
facility: MHAT "Heart and brain" EAD Pleven Department of Neurology Diseases
city: Plovdiv
country: Bulgaria
facility: UMHAT " Kaspela" EOOD, Department of Neurology Diseases
city: Ruse
country: Bulgaria
facility: UMHAT "Kanev Ruse", Department of General and Vascular Neurology
city: Sofia
country: Bulgaria
facility: MHATNP "Sveti Naum" EAD, Neurology Clinic for Movement Disorders, First Department of Neurology Diseases
city: Sofia
country: Bulgaria
facility: MHATNPsy "Sveti Naum" EAD, Intensive Therapy Clinic Of Neurology Diseases
city: Sofia
country: Bulgaria
facility: DCC "Neoclinic" EAD, Cabinet Neurology Diseases
city: Sofia
country: Bulgaria
facility: UMHAT "Alexandrovska" EAD, Clinic of Neurology Diseases, Department of Inherited Degenerative and Immunoinflamatori Diseases at Peripheral Nervous System
city: Sofia
country: Bulgaria
facility: UMHAT "Sveti Ivan Rilski" EAD Sofia Clinic of Neurological Diseases
city: Sofia
country: Bulgaria
facility: UMHAT"Alexandrovska"EAD, Department of Degenerative and Immunoinflamatory Disease of the Central Nervous System
city: Sofia
country: Bulgaria
facility: Central Clinical Base-Medical Institute - Ministry of Interior, Neurology Clinic
city: Sofia
country: Bulgaria
facility: Military Medical Academy - Sofia, Clinic of Neurology Diseases
city: Sofia
country: Bulgaria
facility: Military Medical Academy, Clinic of Functional Diagnostics of Nevous System
city: Varna
country: Bulgaria
facility: UMHAT " Sveta Marina EAD, First Neurology Clinic
city: Bydgoszcz
country: Poland
facility: Nasz Lekarz Ośrodek Badań Klinicznych
city: Bydgoszcz
country: Poland
facility: Specjalistyczna Praktyka Lekarska Paweł Bochniak
city: Lublin
country: Poland
facility: Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
city: Nadarzyn
country: Poland
facility: BioResearch Group Sp. Z o.o
city: Warszawa
country: Poland
facility: Centrum Medyczne NeuroProtect
city: Bucharest
country: Romania
facility: S.C. Sana Monitoring Srl
city: Bucharest
country: Romania
facility: Spitalul Universitar Elias Bucharesti
city: Bucharest
country: Romania
facility: S.C. Quantum Medical Center Srl
city: Bucharest
country: Romania
facility: Spitalul Clinic Colentina Bucharest, Neurologie 2
city: Constanta
country: Romania
facility: Spitalul Clinic Cai Ferate Constanta
city: Chernihiv
country: Ukraine
facility: Chernihiv Regional Hospital, Department of Neurology
city: Dnipro
country: Ukraine
facility: Dnipropetrovsk Municipal Hospital #5, Neurological Department of the inflammatory and demyelinating diseases of CNS
city: Dnipro
country: Ukraine
facility: Ukrainian State Research Institute of Medical and Social Problems of Disability of MOH of Ukraine
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Clinical Hospital, Department of vascular Neurology
city: Kharkiv
country: Ukraine
facility: Kharkiv Regional Clinical Hospital, Department of Neurology
city: Kharkiv
country: Ukraine
facility: Institute of Neurology, Psychiatry and Narcology NAMSU
city: Kyiv
country: Ukraine
facility: Kyiv City Clinical Hospital #4, Department of Neurology
city: Lutsk
country: Ukraine
facility: Volyn Regional Clinical Hospital, Department of Neurology
city: Poltava
country: Ukraine
facility: Poltava Regional Clinical Hospital n.a. Sklifosovskyi, Department of Neurology
city: Uzhgorod
country: Ukraine
facility: Regional Clinical Centre of Neurosurgery and Neurology, Department #2
city: Vinnytsya
country: Ukraine
facility: Vinnytsya Regional Psychoneurology Hospital n.a. Yushchenko, Department of Neurology #3
city: Zaporizhzhya
country: Ukraine
facility: City Clinical Hospital #2, Department of Neurology
city: Zaporizhzhya
country: Ukraine
facility: Zaporizhzhya Regional Clinical Hospital, Department of Neurology #1
Study officials:
affiliation: Immunic AG
name: Andreas Muehler
role: STUDY_DIRECTOR
References:
citation: Fox RJ, Wiendl H, Wolf C, De Stefano N, Sellner J, Gryb V, Rejdak K, Bozhinov PS, Tomakh N, Skrypchenko I, Muehler AR. A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. Ann Clin Transl Neurol. 2022 Jul;9(7):977-987. doi: 10.1002/acn3.51574. Epub 2022 Jun 14.