MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS)

Phase 2

Active, not recruiting

Conditions: Relapsing-Remitting Multiple Sclerosis (RRMS)

Interventions: Drug: IMU-838 (30 mg/day)
Drug: IMU-838 (45 mg/day)
Drug: Placebo
Drug: IMU-838 (10 mg/day)

Registration Number: NCT03846219

Lead Sponsor: Immunic AG

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.

Detailed Description: Not available

Recruitment & Eligibility

Status: ACTIVE_NOT_RECRUITING

Sex: All

Target Recruitment: 210

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
IMU-838 (30 mg/day)	IMU-838 (30 mg/day)	IMU-838 tablet containing 15 mg Vidofludimus calcium (IM90838). Once-daily oral dose of 30 mg consists of 2 tablets IMU-838. Duration: until the end of the main treatment period (24 weeks). In the optional extended treatment period, patients were randomized to receive either 30 mg/day or 45 mg/day IMU-838 (up to 9.5 years for the main trial).
IMU-838 (45 mg/day)	IMU-838 (45 mg/day)	Tablet containing 22.5 mg Vidofludimus calcium (IM90838). Once-daily oral dose of 45 mg consists of 2 tablets. Duration: until the end of the main treatment period (24 weeks). In the optional extended treatment period, patients were randomized to receive either 30 mg/day or 45 mg/day IMU-838.
Placebo	Placebo	Tablet containing no active ingredient. The placebo tablets will be identical to the IMU-838 tablets in terms of appearance, constitution of inactive ingredients, and packaging. Once-daily oral dose consists of 2 active compound-free tablets. Duration: until the end of the main treatment period (24 weeks). The placebo is not applicable in the optional extended treatment period, in which participants who were receiving placebo in the main treatment period were re-randomized to IMU-838 for the extended treatment period.
IMU-838 (10 mg/day) - Cohort 2	IMU-838 (10 mg/day)	Cohort 2 sub-trial: additional sub-trial with a small double-blind, placebo-controlled, randomized, parallel-group assessment of a low IMU-838 dose (i.e. 10 mg/day) to provide additional data for pharmacodynamic modelling. Tablet containing 5 mg Vidofludimus calcium (IM90838). Once-daily oral dose of 10 mg consists of 2 tablets. Duration: until the end of the main treatment period (24 weeks). In the optional extended treatment period, patients were randomized to receive either 30 mg/day or 45 mg/day IMU-838 (up to 8.5 years for the cohort 2 sub-trial).

Primary Outcome Measures

Name	Time	Method
Difference Between 45 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	Up to Week 24	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for baseline volume of T2 lesions, MRI field strength (1.5 or 3.0 Tesla), and baseline number of gadolinium enhancing (Gd+) lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term. Mainly due to the differing number of patients with 3.0 Tesla MRI examinations in each treatment arm, the statistical adjustments (to ensure comparabiltiy) for each individual comparison differed and hence the adjusted mean cumulative number of CUA MRI lesions in each arm (e.g. placebo) differed depending on the comparison (45 mg IMU-838 vs placebo, 30 mg IMU-838 vs placebo, or 45 mg vs 30 mg IMU-838).

Secondary Outcome Measures

Name	Time	Method
Difference Between 30 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	Up to Week 24	This was the key secondary endpoint (hierarchical testing to primary efficacy). MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for baseline volume of T2 lesions, MRI field strength (1.5 or 3.0 Tesla), and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term. Mainly due to the differing number of patients with 3.0 Tesla MRI examinations in each treatment arm, the statistical adjustments (to ensure comparabiltiy) for each individual comparison differed and hence the adjusted mean cumulative number of CUA MRI lesions in each arm (e.g. placebo) differed depending on the comparison (45 mg IMU-838 vs placebo, 30 mg IMU-838 vs placebo, or 45 mg vs 30 mg IMU-838).
Difference Between 45 mg/Day IMU-838 and 30 mg/Day IMU-838 in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	At Week 24	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for baseline volume of T2 lesions, MRI field strength (1.5 or 3.0 Tesla), and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term. Mainly due to the differing number of patients with 3.0 Tesla MRI examinations in each treatment arm, the statistical adjustments (to ensure comparabiltiy) for each individual comparison differed and hence the adjusted mean cumulative number of CUA MRI lesions in each arm (e.g. placebo) differed depending on the comparison (45 mg IMU-838 vs placebo, 30 mg IMU-838 vs placebo, or 45 mg vs 30 mg IMU-838).
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for MRI field strength (1.5 or 3.0 Tesla) and baseline number of Gd+ lesions (0,≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function.
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	Throughout the main treatment period (Day 0 - Week 18)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for baseline volume of T2 lesions, MRI field strength (1.5 or 3.0 Tesla), and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term.
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	Throughout the main treatment period (Day 0 - Week 24)	The endpoint was removed in the statistical analysis plan \[SAP\], since the content was considered the same as the endpoint "T2-lesion load at Weeks 6, 12, 18 and 24 compared to Baseline".
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T2 lesion load was calculated.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T1 lesion load was calculated.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for MRI field strength (1.5 or 3.0 Tesla) and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for MRI field strength (1.5 or 3.0 Tesla) and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. Estimates were adjusted for MRI field strength (1.5 or 3.0 Tesla) and baseline number of Gd+ lesions (0, ≥1) using a generalized linear model with a negative binomial distribution and a logarithmic link function. Log transformation of time from first IMP dose to date of last MRI assessment was used as offset term.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients who did not develop new Gd+ lesions over the 24-week main treatment period was assessed.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients who did not develop new or enlarging T2 lesions over the 24-week main treatment period was assessed.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with CUA lesions at Week 24 was assessed.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with Gd+ lesions at Week 24 was assessed.
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	Throughout the main treatment period (Day 0 - Week 24)	MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with T2 lesions at Week 24 was assessed.
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)	Throughout the main treatment period (Day 0 - Week 24)	The adjusted mean annualized relapse rate during the main treatment period was calculated. Estimates were adjusted for baseline number of Gd+ lesions (0, ≥1) using a Poisson model with a logarithmic link function. Log transformation of real exposure time of main treatment period was used as offset term. All of the following criteria had to be met for a clinical event to qualify as a relapse: 1. Neurological deficit, either newly appearing or re-appearing, with abnormality specified by both neurological abnormality separated by at least 30 days from onset of a preceding relapse AND neurological abnormality lasting for at least 24 hours 2. Absence of fever or known infection (i.e. temperature \[axillary, oral, or intra-auricular\] ≤37.5ºC) 3. Neurological impairment, defined as either increase in at least one of the functional systems of the EDSS OR increase of the total EDSS score. In both cases, the increase in EDSS had to correlate with the patient's reported symptoms.
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	Throughout the main treatment period (Day 0 - Week 24)	The proportion of relapse-free patients up to Week 24 was assessed. Patients with no documented relapse and last assessment of relapse before Week 18 were not included. Patients with no documented relapse up to Week 18 and a missing assessment at Week 24 were regarded as relapse-free patients.
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	Throughout the main treatment period (Day 0 - Week 24)	Since only a total of 39 of 209 patients had a relapse up to Week 24, the median time to relapse could not be calculated.
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)	Baseline, Week 12, and Week 24	The EDSS is a widely used and validated instrument evaluating the functional systems of the CNS to describe disease progression and the efficacy of MS therapy. The composite rating system ranges from 0 (normal neurological status) to 10 (death due to MS) in 0.5-unit increments. An increase in score indicates a worsening.
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)	Week 12 and Week 24	The EDSS is a widely used and validated instrument evaluating the functional systems of the CNS to describe disease progression and the efficacy of MS therapy. The composite rating system ranges from 0 (normal neurological status) to 10 (death due to MS) in 0.5-unit increments. EDSS progression was defined as an increase of the EDSS score compared to Baseline of at least 1.0 point for patients with a baseline EDSS score of 1 to 4.0 or of at least 1.5 points for patients with a baseline EDSS score of 0.
Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels	At Week 24	The cumulative number of CUA MRI lesions up to Week 24 was correlated with quartiles of IMU-838 trough levels at Week 24 of treatment groups IMU-838 30 mg and IMU-838 45 mg.
Number of Participants With AEs	Up to 24 weeks	The number of patients experiencing treatment-emergent adverse events during the main treatment period was assessed.
Number of Participants With Serious AEs	Up to 24 weeks	The number of patients experiencing serious adverse events during the main treatment period was assessed.
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator)	Up to 24 weeks	Abnormal results in laboratory assessments were assessed by the investigator and classified as clinically significant (yes/no). Clinically significantly abnormal values had to be reported as AE, if not already clinically significantly abnormal at Baseline. Treatment-emergent adverse events related to hematological abnormalities and clinical chemistry abnormalities are reported.
Number of Participants With AEs of Special Interest: Red Blood Cell Urine Positive, at Least of Moderate Intensity	Up to 24 weeks	The number of patients diagnosed with red blood cell (RBC) urine positive of at least moderate intensity during the main treatment period were assessed. The evaluation of RBC in urine was to be solely based on findings from microscopic examinations of urinary sediment and not from dipstick reading only. Therefore, all conspicuous dipstick readings were to be followed up by a microscopic examination of urinary sediment. All findings of RBC in urine per high-powered field (HPF) were to be listed as urinalysis abnormalities but not as an AE, if assessed by the investigator as not clinically significant. The investigator was also to assess any increased RBC in urine as not clinically significant, if there were more likely alternatives to explain this finding.
Number of Participants With AEs of Special Interest: Hematuria	Up to 24 weeks	The number of patients diagnosed with hematuria during the main treatment period were assessed.
Number of Participants With AEs of Special Interest: Retroperitoneal Colicky Pain With Suspected or Confirmed Nephrolithiasis	Up to 24 weeks	The number of patients diagnosed with retroperitoneal colicky pain with suspected or confirmed nephrolithiasis during the main treatment period were assessed.
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:	Up to 24 weeks	* Neutropenia * Lymphopenia * Diarrhea * Alopecia * Hemorrhage * Abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), and total bilirubin with both elevations ˃1.5 x ULN and ≥35% elevated compared to Baseline
12-lead Electrocardiogram (ECG): Heart Rate	Up to 24 weeks	The 12-lead ECG was recorded in supine position after at least 5 minutes at rest using the local standard ECG machine. The ECG was analyzed qualitatively (normal or abnormal, if abnormal clinically significant \[yes/no\]). The heart rate, PQ-, QRS-, and QT intervals, as well as the heart rate-corrected QTc interval (according to Bazett's formula) were determined. All procedures were done according to local practice.
12-lead Electrocardiogram (ECG): PQ-interval	Up to 24 weeks	The 12-lead ECG was recorded in supine position after at least 5 minutes at rest using the local standard ECG machine. The ECG was analyzed qualitatively (normal or abnormal, if abnormal clinically significant \[yes/no\]). The heart rate, PQ-, QRS-, and QT intervals, as well as the heart rate-corrected QTc interval (according to Bazett's formula) were determined. All procedures were done according to local practice.
12-lead Electrocardiogram (ECG): QRS-interval	Up to 24 weeks	The 12-lead ECG was recorded in supine position after at least 5 minutes at rest using the local standard ECG machine. The ECG was analyzed qualitatively (normal or abnormal, if abnormal clinically significant \[yes/no\]). The heart rate, PQ-, QRS-, and QT intervals, as well as the heart rate-corrected QTc interval (according to Bazett's formula) were determined. All procedures were done according to local practice.
12-lead Electrocardiogram (ECG): QT-interval	Up to 24 weeks	The 12-lead ECG was recorded in supine position after at least 5 minutes at rest using the local standard ECG machine. The ECG was analyzed qualitatively (normal or abnormal, if abnormal clinically significant \[yes/no\]). The heart rate, PQ-, QRS-, and QT intervals, as well as the heart rate-corrected QTc interval (according to Bazett's formula) were determined. All procedures were done according to local practice.
12-lead Electrocardiogram (ECG): Heart Rate-corrected QTc Interval (According to Bazett's Formula)	Up to 24 weeks	The 12-lead ECG was recorded in supine position after at least 5 minutes at rest using the local standard ECG machine. The ECG was analyzed qualitatively (normal or abnormal, if abnormal clinically significant \[yes/no\]). The heart rate, PQ-, QRS-, and QT intervals, as well as the heart rate-corrected QTc interval (according to Bazett's formula) were determined. All procedures were done according to local practice.
Physical Examination	Up to 24 weeks	Physical examinations covered the following body systems: general appearance, skin, neck (including thyroid), throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular, neurological systems, and, if applicable, others. Any new clinically significant finding compared to Screening Visit 1 had to be documented as AE. Any clinically significant finding at Screening Visit 1 had to be documented in the medical history section of the eCRF. Patients with clinically significant findings in the physical examination post Day 0 are reported.
Vital Signs: Height	at Screening	Height in centimeters was recorded without shoes. Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Vital Signs: Weight (Absolute Change From Baseline at Week 24)	Baseline and 24 weeks	Weight in kilograms was recorded without shoes. Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Vital Signs: Body Temperature (ºC) (Absolute Change From Baseline at Week 24)	Baseline and 24 weeks	Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Vital Signs: Respiratory Rate (Absolute Change From Baseline at Week 24)	Baseline and 24 weeks	Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Vital Signs: Pulse Rates (Absolute Change From Baseline at Week 24)	Baseline and 24 weeks	Pulse had to be measured with the patient in a seated position, after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Vital Signs: Systolic and Diastolic Blood Pressures (Absolute Change From Baseline at Week 24)	Baseline and 24 weeks	Blood pressure (systolic and diastolic) had to be measured with the patient in a seated position, after at least 5 minutes at rest. Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Micro Ribonucleic Acid (miR)-122 Expression	Change from Baseline to 4 hours after first dose	The fold change in miR-122 from pre dose to 4 hours post dose was assessed.
Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine	At Screening Visit 1, at Week 24, and at EoS visit (EoS visit 30 days (+14 days) after last IMP intake)	The presence of JCV-DNA in urine in patients with detectable JCV-DNA in urine at Screening Visit 1, at Week 24, and at end-of-study (EoS) was determined.
Time to Treatment Discontinuation for Any Reason	Up to 24 weeks	The time to treatment discontinuation up to Week 24 for any reason was determined.
Rate of Treatment Discontinuations up to Week 24	at Week 24	The discontinuation rate during the main treatment period was assessed.
Population Pharmacokinetics: Minimum IMU-838 Plasma Concentration Over the Dosing Interval (Cmin)	At Week 6 (3-10 hours post-dose)	One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Population Pharmacokinetics: Maximum IMU-838 Plasma Concentration Over the Dosing Interval (Cmax)	At Week 6 (3-10 hours post-dose)	One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Population Pharmacokinetics: Area Under the IMU-838 Plasma Concentration-time Curve Over the Dosing Interval (AUC0-τ)	At Week 6 (3-10 hours post-dose)	One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Population Pharmacokinetics: IMU-838 Apparent Clearance Following Oral Dosing (CL/F)	At Week 6 (3-10 hours post-dose)	One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Population Pharmacokinetics: IMU-838 Apparent Volume of Distribution (V/F)	At Week 6 (3-10 hours post-dose)	One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Plasma Trough Levels of IMU-838	At Day 7 and Weeks 6, 12, 18, and 24	Plasma trough levels of IMU-838 were assessed at Day 7 and at Weeks 6, 12, 18, and 24.
Changes From Baseline in Th1 Lymphocyte Subset as Measured by Flow Cytometry	At Weeks 6 and 24 (in selected Biomarker Centers only)	Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Changes From Baseline in Th17 Lymphocyte Subset as Measured by Flow Cytometry	At Weeks 6 and 24 (in selected Biomarker Centers only)	Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Changes From Baseline in Treg Lymphocyte Subset as Measured by Flow Cytometry	At Weeks 6 and 24 (in selected Biomarker Centers only)	Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Changes From Baseline in Serum Neurofilament	At Week 6 and Week 24	The percentage change from Baseline in serum neurofilament was calculated.
Treatment Satisfaction Questionnaire for Medication (TSQM)	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	The TSQM is a reliable and valid instrument to assess patients' satisfaction with medication comprising 14 items across 4 domains: side effects, performance, convenience and global satisfaction. All items have 5 to 7 possible answers, except for item 4 (2 answers). Item scores for each domain are summed and transformed to a scale from 0 (extremely dissatisfied) to 100 (extremely satisfied).
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.	Baseline, Week 6, Week 12, Week 18, and Week 24	This endpoint was added in statistical analysis plan Version 2.0. Results of the brain atrophy analysis included biologically implausible changes (including changes of more than 1% over 24 weeks) in all treatment groups. Hence, the brain volume changes were considered technically inadequate for any conclusions of a treatment effect of IMU-838 versus placebo.

Trial Locations

Locations (38): MHAT Pulse AD, Department of Neurology Diseases
🇧🇬
Blagoevgrad, Bulgaria
UMHAT " Kaspela" EOOD, Department of Neurology Diseases
🇧🇬
Plovdiv, Bulgaria
UMHAT "Kanev Ruse", Department of General and Vascular Neurology
🇧🇬
Ruse, Bulgaria
MHAT "Heart and brain" EAD Pleven Department of Neurology Diseases
🇧🇬
Pleven, Bulgaria
MHATNP "Sveti Naum" EAD, Neurology Clinic for Movement Disorders, First Department of Neurology Diseases
🇧🇬
Sofia, Bulgaria
DCC "Neoclinic" EAD, Cabinet Neurology Diseases
🇧🇬
Sofia, Bulgaria
MHATNPsy "Sveti Naum" EAD, Intensive Therapy Clinic Of Neurology Diseases
🇧🇬
Sofia, Bulgaria
UMHAT "Sveti Ivan Rilski" EAD Sofia Clinic of Neurological Diseases
🇧🇬
Sofia, Bulgaria
UMHAT "Alexandrovska" EAD, Clinic of Neurology Diseases, Department of Inherited Degenerative and Immunoinflamatori Diseases at Peripheral Nervous System
🇧🇬
Sofia, Bulgaria
Military Medical Academy - Sofia, Clinic of Neurology Diseases
🇧🇬
Sofia, Bulgaria
Nasz Lekarz Ośrodek Badań Klinicznych
🇵🇱
Bydgoszcz, Poland
Military Medical Academy, Clinic of Functional Diagnostics of Nevous System
🇧🇬
Sofia, Bulgaria
UMHAT " Sveta Marina EAD, First Neurology Clinic
🇧🇬
Varna, Bulgaria
Indywidualna Praktyka Lekarska Prof. Konrad Rejdak
🇵🇱
Lublin, Poland
BioResearch Group Sp. Z o.o
🇵🇱
Nadarzyn, Poland
Centrum Medyczne NeuroProtect
🇵🇱
Warszawa, Poland
S.C. Sana Monitoring Srl
🇷🇴
Bucharest, Romania
Spitalul Clinic Colentina Bucharest, Neurologie 2
🇷🇴
Bucharest, Romania
S.C. Quantum Medical Center Srl
🇷🇴
Bucharest, Romania
Spitalul Universitar Elias Bucharesti
🇷🇴
Bucharest, Romania
Spitalul Clinic Cai Ferate Constanta
🇷🇴
Constanta, Romania
Chernihiv Regional Hospital, Department of Neurology
🇺🇦
Chernihiv, Ukraine
Ukrainian State Research Institute of Medical and Social Problems of Disability of MOH of Ukraine
🇺🇦
Dnipro, Ukraine
Dnipropetrovsk Municipal Hospital #5, Neurological Department of the inflammatory and demyelinating diseases of CNS
🇺🇦
Dnipro, Ukraine
Regional Clinical Hospital, Department of vascular Neurology
🇺🇦
Ivano-Frankivsk, Ukraine
Kharkiv Regional Clinical Hospital, Department of Neurology
🇺🇦
Kharkiv, Ukraine
Institute of Neurology, Psychiatry and Narcology NAMSU
🇺🇦
Kharkiv, Ukraine
Volyn Regional Clinical Hospital, Department of Neurology
🇺🇦
Lutsk, Ukraine
Kyiv City Clinical Hospital #4, Department of Neurology
🇺🇦
Kyiv, Ukraine
Poltava Regional Clinical Hospital n.a. Sklifosovskyi, Department of Neurology
🇺🇦
Poltava, Ukraine
Regional Clinical Centre of Neurosurgery and Neurology, Department #2
🇺🇦
Uzhgorod, Ukraine
City Clinical Hospital #2, Department of Neurology
🇺🇦
Zaporizhzhya, Ukraine
Vinnytsya Regional Psychoneurology Hospital n.a. Yushchenko, Department of Neurology #3
🇺🇦
Vinnytsya, Ukraine
Zaporizhzhya Regional Clinical Hospital, Department of Neurology #1
🇺🇦
Zaporizhzhya, Ukraine
UMHAT"Alexandrovska"EAD, Department of Degenerative and Immunoinflamatory Disease of the Central Nervous System
🇧🇬
Sofia, Bulgaria
UMHAT "Dr.Georgi Stranski" EAD Pleven Department of Professional Diseases
🇧🇬
Pleven, Bulgaria
Central Clinical Base-Medical Institute - Ministry of Interior, Neurology Clinic
🇧🇬
Sofia, Bulgaria
Specjalistyczna Praktyka Lekarska Paweł Bochniak
🇵🇱
Bydgoszcz, Poland

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neurologylive.com

3 months ago

Phase 3 ENSURE Program of Vidofludimus Calcium Continues Following Positive Futility Analysis

Immunic's IDMC reviewed interim data from the phase 3 ENSURE program assessing vidofludimus calcium in relapsing multiple sclerosis (RMS), advising trials continue as planned. ENSURE includes two identical trials (ENSURE-1, ENSURE-2) with time to first relapse up to 72 weeks as the primary endpoint. The IDMC found no futility, suggesting the planned sample size is appropriate for the primary endpoint. Both trials are expected to complete in 2026.