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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03846219
Recruitment Status : Active, not recruiting
First Posted : February 19, 2019
Results First Posted : July 23, 2021
Last Update Posted : February 11, 2022
Sponsor:
Information provided by (Responsible Party):
Immunic AG

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition 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)
Enrollment 210
Recruitment Details

The trial consists of a main trial (Cohort 1) and a sub-trial (Cohort 2): Cohort 1 compares 30 mg IMU-838, 45 mg IMU-838 and placebo and assesses the primary and key secondary endpoints; Cohort 2 compares 10 mg/day IMU-838 with placebo. The main trial consists of a blinded 24-week main treatment period and an optional initially blinded, then open-label extended treatment period of up to 9.5 years (currently ongoing).

Results of the Cohort 1 main treatment period are reported.

Pre-assignment Details Patients were randomized in a 1:1:1 ratio to once-daily oral treatment with 30 mg IMU-838, 45 mg IMU-838, or matching placebo for 24 weeks. At Week 24 (end-of-main treatment period), patients had the option to continue into the extended treatment period if they met respective eligibility criteria including an magnetic resonance imaging (MRI) scan.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days. During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days. During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Period Title: Overall Study
Started [1] 72 69 69
Patients Treated 71 69 69
Completed 69 65 64
Not Completed 3 4 5
Reason Not Completed
Withdrawal by Subject             3             2             2
Fulfilled hepatoxicity-related stopping rules             0             2             1
Physician Decision             0             0             2
[1]
Patients randomized
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo Total
Hide Arm/Group Description

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Total of all reporting groups
Overall Number of Baseline Participants 72 69 69 210
Hide Baseline Analysis Population Description
Patients randomized
Age, Continuous   [1] 
Median (Full Range)
Unit of measure:  Years
Number Analyzed 71 participants 69 participants 69 participants 209 participants
38.0
(18 to 55)
36.0
(21 to 51)
37.0
(21 to 55)
36.0
(18 to 55)
[1]
Measure Analysis Population Description: Full analysis set (FAS, the FAS consisted of all randomized patients who received at least 1 dose of the investigational medicinal product).
Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 69 participants 69 participants 209 participants
Female
40
  56.3%
50
  72.5%
46
  66.7%
136
  65.1%
Male
31
  43.7%
19
  27.5%
23
  33.3%
73
  34.9%
[1]
Measure Analysis Population Description: Full analysis set
Ethnicity (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 69 participants 69 participants 209 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
71
 100.0%
69
 100.0%
69
 100.0%
209
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Full analysis set
Race (NIH/OMB)   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 69 participants 69 participants 209 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
White
71
 100.0%
69
 100.0%
69
 100.0%
209
 100.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
[1]
Measure Analysis Population Description: Full analysis set
Region of Enrollment   [1] 
Measure Type: Number
Unit of measure:  Participants
Romania Number Analyzed 72 participants 69 participants 69 participants 210 participants
3 2 1 6
Ukraine Number Analyzed 72 participants 69 participants 69 participants 210 participants
40 36 42 118
Poland Number Analyzed 72 participants 69 participants 69 participants 210 participants
11 6 9 26
Bulgaria Number Analyzed 72 participants 69 participants 69 participants 210 participants
18 25 17 60
[1]
Measure Analysis Population Description: Patients randomized
Body mass index   [1] 
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 71 participants 69 participants 69 participants 209 participants
23.491  (5.311) 24.786  (5.067) 24.462  (4.758) 24.239  (5.059)
[1]
Measure Analysis Population Description: Full analysis set
Expanded Disability Status Scale   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Units on a scale
Number Analyzed 71 participants 69 participants 69 participants 209 participants
2.65  (0.83) 2.56  (0.96) 2.73  (0.90) 2.65  (0.90)
[1]
Measure Description: The Expanded Disability Status Scale composite rating system ranges from 0 (normal neurological status) to 10 (death due to MS) in 0.5-unit increments. EDSS steps 1.0 to 4.5 refer to a functional status of patients with MS with some limitations within at least one functional system, but still able to walk without any aid. EDSS steps 5.0 to 9.5 are defined by the impairment to walk.
[2]
Measure Analysis Population Description: Full analysis set
Gadolinium enhancing (Gd+) lesions   [1] 
Mean (Standard Deviation)
Unit of measure:  Lesions
Number Analyzed 71 participants 69 participants 69 participants 209 participants
1.4  (2.4) 0.9  (1.3) 1.2  (2.1) 1.2  (2.0)
[1]
Measure Analysis Population Description: Full analysis set
T2 lesion load   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Cm^3
Number Analyzed 71 participants 69 participants 69 participants 209 participants
13.341  (15.079) 13.918  (12.946) 11.980  (10.417) 13.082  (12.940)
[1]
Measure Description: The T2 lesion load per participant was documented in the Case Report Form. In the analysis, a mean across all participants in each arm was calculated.
[2]
Measure Analysis Population Description: Full analysis set
MRI field strength   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 69 participants 69 participants 209 participants
1.5 Tesla
65
  91.5%
66
  95.7%
67
  97.1%
198
  94.7%
3.0 Tesla
6
   8.5%
3
   4.3%
2
   2.9%
11
   5.3%
[1]
Measure Analysis Population Description: Full analysis set
Duration of disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 71 participants 69 participants 69 participants 209 participants
<=4 years
37
  52.1%
37
  53.6%
37
  53.6%
111
  53.1%
>4 years
34
  47.9%
32
  46.4%
32
  46.4%
98
  46.9%
[1]
Measure Analysis Population Description: Full analysis set
1.Primary Outcome
Title Difference Between 45 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
Hide Description 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).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisting of all randomized patients who received at least 1 dose of the investigational medicinal product (IMP).
Arm/Group Title IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 69 69
Mean (95% Confidence Interval)
Unit of Measure: CUA MRI lesions
2.4
(1.1 to 4.9)
6.3
(2.8 to 13.9)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMU-838 (45 mg/Day), Placebo
Comments H0: cumulative number of CUA MRI lesions up to Week 24 with 45 mg IMU-838 equal to or higher than that with placebo. A generalized linear model with a negative binomial distribution and logarithmic link function was used. Log transformation of time from 1st IMP dose to date of last MRI assessment was used as offset term. 51 patients per group were necessary to have 80% power to detect a difference of 3.5 in mean event rate with a significance level 0.1, 1-sided.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0002
Comments A one-sided alpha level of 0.1 was used.
Method generalized linear model
Comments 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).
Method of Estimation Estimation Parameter rate ratio
Estimated Value 0.38
Confidence Interval (2-Sided) 95%
0.22 to 0.64
Estimation Comments Rate ratio of 45 mg IMU-838 / placebo
2.Secondary Outcome
Title Difference Between 30 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
Hide Description 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).
Time Frame Up to Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisting of all randomized patients who received at least 1 dose of the IMP.
Arm/Group Title IMU-838 (30 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69
Mean (95% Confidence Interval)
Unit of Measure: CUA MRI lesions
4.0
(2.2 to 7.2)
13.2
(6.6 to 26.4)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection IMU-838 (30 mg/Day), Placebo
Comments A generalized linear model with a negative binomial distribution and logarithmic link function was used. Log transformation of time from 1st IMP dose to date of last MRI assessment was used as offset term.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <.0001
Comments A hierarchical testing procedure with a one-sided alpha level of 0.1 was used.
Method Generalized linear model
Comments 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).
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 0.30
Confidence Interval (2-Sided) 95%
0.17 to 0.53
Estimation Comments Rate ratio of 30 mg IMU-838 / placebo
3.Secondary Outcome
Title Difference Between 45 mg/Day IMU-838 and 30 mg/Day IMU-838 in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
Hide Description 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).
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
FAS consisting of all randomized patients who received at least 1 dose of the investigational medicinal product.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day)
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69
Mean (95% Confidence Interval)
Unit of Measure: CUA MRI lesions
4.2
(2.5 to 7.1)
4.4
(2.4 to 8.1)
4.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (95% Confidence Interval)
Unit of Measure: CUA MRI lesions
Week 6 Number Analyzed 69 participants 67 participants 66 participants
1.1
(0.5 to 2.1)
0.8
(0.4 to 1.8)
3.2
(1.5 to 6.6)
Week 12 Number Analyzed 68 participants 65 participants 68 participants
1.3
(0.7 to 2.3)
1.2
(0.6 to 2.6)
3.4
(1.7 to 7.0)
Week 18 Number Analyzed 70 participants 64 participants 65 participants
1.3
(0.7 to 2.5)
0.8
(0.3 to 1.7)
3.2
(1.5 to 6.6)
Week 24 Number Analyzed 69 participants 65 participants 64 participants
1.6
(0.8 to 3.5)
1.6
(0.6 to 4.4)
3.7
(1.5 to 9.3)
5.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 18)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (95% Confidence Interval)
Unit of Measure: CUA MRI lesions
Week 6 Number Analyzed 69 participants 67 participants 66 participants
0.8
(0.4 to 1.7)
0.6
(0.3 to 1.4)
2.5
(1.1 to 5.5)
Week 12 Number Analyzed 71 participants 69 participants 69 participants
1.7
(1.0 to 3.0)
1.6
(0.9 to 3.2)
5.3
(2.8 to 10.0)
Week 18 Number Analyzed 71 participants 69 participants 69 participants
2.7
(1.6 to 4.5)
2.5
(1.4 to 4.6)
8.0
(4.5 to 14.4)
6.Secondary Outcome
Title 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
Hide Description 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".
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
This measure was not analyzed because it was determined to be redundant with Outcome Measure 7. No data are available to be reported.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
7.Secondary Outcome
Title 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
Hide Description MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T2 lesion load was calculated.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (95% Confidence Interval)
Unit of Measure: % change from Baseline
Week 6 Number Analyzed 69 participants 67 participants 66 participants
2.2
(-0.4 to 3.0)
1.7
(0.3 to 3.6)
2.4
(0.9 to 4.5)
Week 12 Number Analyzed 68 participants 65 participants 68 participants
3.3
(2.2 to 4.9)
3.4
(2.2 to 5.1)
4.7
(1.8 to 6.6)
Week 18 Number Analyzed 70 participants 64 participants 65 participants
4.9
(2.3 to 7.3)
4.6
(3.4 to 6.2)
7.1
(4.8 to 8.9)
Week 24 Number Analyzed 69 participants 65 participants 64 participants
6.6
(3.5 to 9.7)
7.3
(4.2 to 8.7)
9.0
(7.1 to 12.0)
8.Secondary Outcome
Title 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
Hide Description MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T1 lesion load was calculated.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (95% Confidence Interval)
Unit of Measure: % change from Baseline
Week 6 Number Analyzed 68 participants 67 participants 63 participants
-2.9
(-4.9 to -0.9)
-0.4
(-3.3 to 0.8)
-4.2
(-5.7 to -1.2)
Week 12 Number Analyzed 67 participants 65 participants 65 participants
-4.0
(-5.7 to -1.4)
-1.6
(-4.1 to 0.0)
0.0
(-2.0 to 0.8)
Week 18 Number Analyzed 69 participants 64 participants 62 participants
-3.8
(-5.6 to -1.4)
-1.4
(-3.8 to 1.8)
-0.7
(-2.1 to 1.0)
Week 24 Number Analyzed 68 participants 65 participants 61 participants
-5.7
(-7.6 to -1.7)
-0.9
(-3.6 to 0.0)
-0.8
(-2.3 to 0.7)
9.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (95% Confidence Interval)
Unit of Measure: Gd+ lesions
Week 6 Number Analyzed 69 participants 67 participants 66 participants
1.0
(0.5 to 2.0)
0.8
(0.3 to 1.7)
2.8
(1.3 to 6.2)
Week 12 Number Analyzed 71 participants 69 participants 69 participants
2.1
(1.2 to 3.7)
1.7
(0.9 to 3.3)
6.2
(3.2 to 11.9)
Week 18 Number Analyzed 71 participants 69 participants 69 participants
3.1
(1.8 to 5.2)
2.4
(1.3 to 4.5)
9.1
(4.9 to 16.8)
Week 24 Number Analyzed 71 participants 69 participants 69 participants
4.5
(2.7 to 7.7)
4.0
(2.1 to 7.8)
13.0
(6.8 to 24.5)
10.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (95% Confidence Interval)
Unit of Measure: T2 lesions
Week 6 Number Analyzed 69 participants 67 participants 66 participants
0.8
(0.4 to 1.7)
0.7
(0.3 to 1.5)
2.6
(1.2 to 5.8)
Week 12 Number Analyzed 71 participants 69 participants 69 participants
1.8
(1.1 to 3.1)
1.8
(1.0 to 3.5)
6.0
(3.2 to 11.2)
Week 18 Number Analyzed 71 participants 69 participants 69 participants
2.8
(1.7 to 4.5)
2.7
(1.5 to 4.9)
8.8
(5.0 to 15.5)
Week 24 Number Analyzed 71 participants 69 participants 69 participants
4.1
(2.5 to 6.6)
4.2
(2.3 to 7.7)
11.9
(6.7 to 21.1)
11.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (95% Confidence Interval)
Unit of Measure: T1 lesions
Week 6 Number Analyzed 69 participants 67 participants 66 participants
0.3
(0.1 to 0.8)
0.2
(0.1 to 0.6)
1.1
(0.4 to 3.4)
Week 12 Number Analyzed 71 participants 69 participants 69 participants
0.6
(0.3 to 1.2)
0.6
(0.3 to 1.3)
2.5
(1.1 to 5.6)
Week 18 Number Analyzed 71 participants 69 participants 69 participants
1.0
(0.6 to 1.9)
1.0
(0.5 to 1.9)
3.9
(2.0 to 7.4)
Week 24 Number Analyzed 71 participants 69 participants 69 participants
1.4
(0.8 to 2.4)
1.5
(0.8 to 2.9)
4.7
(2.5 to 8.8)
12.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
42
  59.2%
34
  49.3%
26
  37.7%
13.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
36
  50.7%
29
  42.0%
22
  31.9%
14.Secondary Outcome
Title 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
Hide Description MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with CUA lesions at Week 24 was assessed.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations at Week 24
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 69 65 64
Measure Type: Count of Participants
Unit of Measure: Participants
15
  21.7%
19
  29.2%
25
  39.1%
15.Secondary Outcome
Title 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
Hide Description MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with Gd+ lesions at Week 24 was assessed.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations at Week 24.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 69 65 64
Measure Type: Count of Participants
Unit of Measure: Participants
10
  14.5%
16
  24.6%
25
  39.1%
16.Secondary Outcome
Title 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
Hide Description MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with T2 lesions at Week 24 was assessed.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations in this analysis.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 69 65 64
Measure Type: Count of Participants
Unit of Measure: Participants
15
  21.7%
18
  27.7%
21
  32.8%
17.Secondary Outcome
Title 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)
Hide Description

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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo (Compared With 30 and 45 mg IMU-838) IMU-838 Combined Placebo (Compared With IMU-838 Combined)
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Groups 30 mg IMU-838 and 45 mg IMU-838 combined
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69 140 69
Mean (95% Confidence Interval)
Unit of Measure: relapses per person-years
0.39
(0.22 to 0.69)
0.48
(0.28 to 0.82)
0.53
(0.32 to 0.89)
0.43
(0.29 to 0.62)
0.54
(0.34 to 0.86)
18.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Patients analyzed
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo IMU-838 Combined
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Groups 30 mg IMU-838 and 45 mg IMU-838 combined
Overall Number of Participants Analyzed 70 67 67 137
Measure Type: Count of Participants
Unit of Measure: Participants
60
  85.7%
54
  80.6%
51
  76.1%
114
  83.2%
19.Secondary Outcome
Title 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
Hide Description 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.
Time Frame Throughout the main treatment period (Day 0 - Week 24)
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: days
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
NA [1] 
(NA to NA)
[1]
The median time to relapse could not be calculated.
20.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Baseline, Week 12, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (Standard Deviation)
Unit of Measure: score on a scale
Week 12 Number Analyzed 70 participants 67 participants 69 participants
-0.01  (0.28) 0.00  (0.42) 0.03  (0.38)
Week 24 Number Analyzed 67 participants 65 participants 64 participants
0.01  (0.25) 0.00  (0.39) 0.08  (0.39)
21.Secondary Outcome
Title 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)
Hide Description 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.
Time Frame Week 12 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
Up to Week 12 Number Analyzed 70 participants 67 participants 69 participants
6
   8.6%
7
  10.4%
9
  13.0%
Up to Week 24 Number Analyzed 68 participants 66 participants 65 participants
8
  11.8%
8
  12.1%
15
  23.1%
22.Secondary Outcome
Title Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels
Hide Description 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.
Time Frame At Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day)
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 67 64
Mean (Standard Deviation)
Unit of Measure: CUA MRI lesions
1st quartile of IMU-838 trough level 1.1  (2.0) 1.6  (3.1)
2nd quartile of IMU-838 trough level 2.2  (4.9) 1.8  (2.8)
3rd quartile of IMU-838 trough level 4.4  (5.8) 2.0  (2.2)
4th quartile of IMU-838 trough level 6.8  (14.7) 5.3  (9.8)
23.Secondary Outcome
Title Number of Participants With AEs
Hide Description The number of patients experiencing treatment-emergent adverse events during the main treatment period was assessed.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set consisting of all randomized patients who received at least 1 dose of IMP.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
32
  45.1%
28
  40.6%
30
  43.5%
24.Secondary Outcome
Title Number of Participants With Serious AEs
Hide Description The number of patients experiencing serious adverse events during the main treatment period was assessed.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety data set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
2
   2.8%
0
   0.0%
1
   1.4%
25.Secondary Outcome
Title Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator)
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
Anemia
0
   0.0%
0
   0.0%
1
   1.4%
Iron deficiency anemia
0
   0.0%
0
   0.0%
2
   2.9%
Leukopenia
0
   0.0%
0
   0.0%
1
   1.4%
Neutropenia
0
   0.0%
0
   0.0%
1
   1.4%
Alanine aminotransferase increased
1
   1.4%
0
   0.0%
2
   2.9%
Aspartate aminotransferase increased
1
   1.4%
0
   0.0%
1
   1.4%
Blood bilirubin increased
1
   1.4%
0
   0.0%
0
   0.0%
Blood creatine phosphokinase increased
2
   2.8%
0
   0.0%
0
   0.0%
Blood creatinine increased
1
   1.4%
0
   0.0%
0
   0.0%
C-reactive protein increased
0
   0.0%
1
   1.4%
0
   0.0%
Hepatic enzyme increased
1
   1.4%
2
   2.9%
1
   1.4%
Lipase increased
0
   0.0%
0
   0.0%
1
   1.4%
Transaminases increased
0
   0.0%
1
   1.4%
0
   0.0%
Hypertriglyceridemia
1
   1.4%
0
   0.0%
1
   1.4%
26.Secondary Outcome
Title Number of Participants With AEs of Special Interest: Red Blood Cell Urine Positive, at Least of Moderate Intensity
Hide Description

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.

Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
0
   0.0%
27.Secondary Outcome
Title Number of Participants With AEs of Special Interest: Hematuria
Hide Description The number of patients diagnosed with hematuria during the main treatment period were assessed.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
0
   0.0%
1
   1.4%
28.Secondary Outcome
Title Number of Participants With AEs of Special Interest: Retroperitoneal Colicky Pain With Suspected or Confirmed Nephrolithiasis
Hide Description The number of patients diagnosed with retroperitoneal colicky pain with suspected or confirmed nephrolithiasis during the main treatment period were assessed.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
1
   1.4%
0
   0.0%
0
   0.0%
29.Secondary Outcome
Title 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:
Hide Description
  • 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
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
Neutropenia
0
   0.0%
0
   0.0%
1
   1.4%
Lymphopenia
0
   0.0%
0
   0.0%
0
   0.0%
Diarrhea
0
   0.0%
0
   0.0%
0
   0.0%
Alopecia
3
   4.2%
1
   1.4%
0
   0.0%
Hemorrhage
0
   0.0%
0
   0.0%
0
   0.0%
ALT >1.5 x ULN AND representing a % change from Baseline ≥35%
2
   2.8%
4
   5.8%
5
   7.2%
AST >1.5 x ULN AND representing a % change from Baseline ≥35%
1
   1.4%
3
   4.3%
4
   5.8%
GGT >1.5 x ULN AND representing a % change from Baseline ≥35%
3
   4.2%
2
   2.9%
1
   1.4%
Total bilirubin >1.5 x ULN AND representing a % change from Baseline ≥35%
0
   0.0%
0
   0.0%
0
   0.0%
30.Secondary Outcome
Title 12-lead Electrocardiogram (ECG): Heart Rate
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: beats per minute
Screening 1 Number Analyzed 71 participants 69 participants 69 participants
67.0
(45 to 100)
68.0
(51 to 93)
67.0
(46 to 97)
Week 24 Number Analyzed 66 participants 64 participants 64 participants
69.5
(46 to 120)
69.0
(43 to 116)
70.0
(46 to 105)
31.Secondary Outcome
Title 12-lead Electrocardiogram (ECG): PQ-interval
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: msec
Screening 1 Number Analyzed 71 participants 69 participants 69 participants
147.0
(95 to 448)
140.0
(87 to 200)
150.0
(95 to 200)
Week 24 Number Analyzed 66 participants 64 participants 64 participants
146.5
(77 to 247)
146.0
(100 to 213)
150.5
(92 to 202)
32.Secondary Outcome
Title 12-lead Electrocardiogram (ECG): QRS-interval
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: msec
Screening 1 Number Analyzed 71 participants 69 participants 69 participants
90.0
(60 to 148)
86.0
(60 to 135)
90.0
(66 to 112)
Week 24 Number Analyzed 66 participants 64 participants 64 participants
90.0
(60 to 128)
86.0
(60 to 120)
91.0
(60 to 113)
33.Secondary Outcome
Title 12-lead Electrocardiogram (ECG): QT-interval
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: msec
Screening 1 Number Analyzed 71 participants 69 participants 69 participants
383.0
(310 to 514)
380.0
(320 to 447)
387.0
(335 to 448)
Week 24 Number Analyzed 66 participants 64 participants 64 participants
376.5
(71 to 472)
374.5
(286 to 472)
385.0
(310 to 448)
34.Secondary Outcome
Title 12-lead Electrocardiogram (ECG): Heart Rate-corrected QTc Interval (According to Bazett's Formula)
Hide Description 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.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: msec
Screening 1 Number Analyzed 71 participants 69 participants 69 participants
407.0
(325 to 500)
404.0
(340 to 483)
410.0
(361 to 468)
Week 24 Number Analyzed 66 participants 64 participants 64 participants
407.0
(77 to 478)
404.0
(283 to 467)
409.0
(353 to 483)
35.Secondary Outcome
Title Physical Examination
Hide Description

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.

Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
0
   0.0%
1
   1.4%
3
   4.3%
36.Secondary Outcome
Title Vital Signs: Height
Hide Description 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.
Time Frame at Screening
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (Full Range)
Unit of Measure: cm
170.0
(154 to 198)
167.0
(154 to 188)
168.0
(149 to 192)
37.Secondary Outcome
Title Vital Signs: Weight (Absolute Change From Baseline at Week 24)
Hide Description 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.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 66 65 64
Median (Full Range)
Unit of Measure: kg
0.00
(-18.2 to 8.6)
0.00
(-7.0 to 7.5)
0.00
(-11.0 to 12.5)
38.Secondary Outcome
Title Vital Signs: Body Temperature (ºC) (Absolute Change From Baseline at Week 24)
Hide Description Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 67 65 64
Median (Full Range)
Unit of Measure: °C
0.00
(-0.8 to 1.6)
0.00
(-0.7 to 0.7)
0.00
(-0.8 to 0.4)
39.Secondary Outcome
Title Vital Signs: Respiratory Rate (Absolute Change From Baseline at Week 24)
Hide Description Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.
Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 67 65 64
Median (Full Range)
Unit of Measure: breaths/min
0.0
(-4 to 6)
0.0
(-6 to 4)
0.0
(-3 to 9)
40.Secondary Outcome
Title Vital Signs: Pulse Rates (Absolute Change From Baseline at Week 24)
Hide Description

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.

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 67 65 64
Median (Full Range)
Unit of Measure: beats per minute
0.0
(-24 to 16)
0.0
(-30 to 24)
-1.0
(-18 to 22)
41.Secondary Outcome
Title Vital Signs: Systolic and Diastolic Blood Pressures (Absolute Change From Baseline at Week 24)
Hide Description

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.

Time Frame Baseline and 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 67 65 64
Median (Full Range)
Unit of Measure: mmHg
Systolic blood pressure
0.0
(-36 to 20)
0.0
(-30 to 30)
0.0
(-22 to 30)
Diastolic blood pressure
0.0
(-25 to 22)
0.0
(-20 to 30)
0.0
(-26 to 20)
42.Secondary Outcome
Title Micro Ribonucleic Acid (miR)-122 Expression
Hide Description The fold change in miR-122 from pre dose to 4 hours post dose was assessed.
Time Frame Change from Baseline to 4 hours after first dose
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 69 67 67
Median (Full Range)
Unit of Measure: fold change
0.727
(0.12 to 63.23)
0.991
(0.19 to 53.75)
0.946
(0.12 to 50.11)
43.Secondary Outcome
Title Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine
Hide Description 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 Frame At Screening Visit 1, at Week 24, and at EoS visit (EoS visit 30 days (+14 days) after last IMP intake)
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
Screening 1 Number Analyzed 69 participants 68 participants 67 participants
32
  46.4%
27
  39.7%
29
  43.3%
Week 24 Number Analyzed 65 participants 62 participants 63 participants
27
  41.5%
16
  25.8%
18
  28.6%
End-of-study Number Analyzed 1 participants 3 participants 4 participants
0
   0.0%
1
  33.3%
1
  25.0%
44.Secondary Outcome
Title Time to Treatment Discontinuation for Any Reason
Hide Description The time to treatment discontinuation up to Week 24 for any reason was determined.
Time Frame Up to 24 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Patients with observations
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 2 4 5
Median (Full Range)
Unit of Measure: days
106.5
(43 to 170)
66.5
(47 to 178)
98.0
(85 to 139)
45.Secondary Outcome
Title Rate of Treatment Discontinuations up to Week 24
Hide Description The discontinuation rate during the main treatment period was assessed.
Time Frame at Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Measure Type: Count of Participants
Unit of Measure: Participants
2
   2.8%
4
   5.8%
5
   7.2%
46.Secondary Outcome
Title Population Pharmacokinetics: Minimum IMU-838 Plasma Concentration Over the Dosing Interval (Cmin)
Hide Description One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Time Frame At Week 6 (3-10 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Data have not yet been analyzed.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
47.Secondary Outcome
Title Population Pharmacokinetics: Maximum IMU-838 Plasma Concentration Over the Dosing Interval (Cmax)
Hide Description One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Time Frame At Week 6 (3-10 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Data have not yet been analyzed.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
48.Secondary Outcome
Title Population Pharmacokinetics: Area Under the IMU-838 Plasma Concentration-time Curve Over the Dosing Interval (AUC0-τ)
Hide Description One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Time Frame At Week 6 (3-10 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Data have not yet been analyzed.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
49.Secondary Outcome
Title Population Pharmacokinetics: IMU-838 Apparent Clearance Following Oral Dosing (CL/F)
Hide Description One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Time Frame At Week 6 (3-10 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Data have not yet been analyzed.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
50.Secondary Outcome
Title Population Pharmacokinetics: IMU-838 Apparent Volume of Distribution (V/F)
Hide Description One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.
Time Frame At Week 6 (3-10 hours post-dose)
Hide Outcome Measure Data
Hide Analysis Population Description
Data have not yet been analyzed.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
51.Secondary Outcome
Title Plasma Trough Levels of IMU-838
Hide Description Plasma trough levels of IMU-838 were assessed at Day 7 and at Weeks 6, 12, 18, and 24.
Time Frame At Day 7 and Weeks 6, 12, 18, and 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day)
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69
Median (Full Range)
Unit of Measure: μg/mL
Day 7 Number Analyzed 70 participants 69 participants
2.155
(0.90 to 8.96)
3.100
(0.12 to 7.89)
Week 6 Number Analyzed 71 participants 66 participants
4.320
(0.00 to 15.70)
6.240
(0.00 to 18.30)
Week 12 Number Analyzed 69 participants 67 participants
4.160
(0.00 to 12.40)
5.420
(0.00 to 14.00)
Week 18 Number Analyzed 70 participants 65 participants
4.165
(0.00 to 12.10)
5.990
(0.00 to 15.00)
Week 24 Number Analyzed 67 participants 64 participants
4.010
(0.00 to 8.14)
5.700
(0.00 to 16.30)
52.Secondary Outcome
Title Changes From Baseline in Th1 Lymphocyte Subset as Measured by Flow Cytometry
Hide Description Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Time Frame At Weeks 6 and 24 (in selected Biomarker Centers only)
Hide Outcome Measure Data
Hide Analysis Population Description
Changes from Baseline in Th1 lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
53.Secondary Outcome
Title Changes From Baseline in Th17 Lymphocyte Subset as Measured by Flow Cytometry
Hide Description Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Time Frame At Weeks 6 and 24 (in selected Biomarker Centers only)
Hide Outcome Measure Data
Hide Analysis Population Description
Changes from Baseline in Th17 lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
54.Secondary Outcome
Title Changes From Baseline in Treg Lymphocyte Subset as Measured by Flow Cytometry
Hide Description Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Time Frame At Weeks 6 and 24 (in selected Biomarker Centers only)
Hide Outcome Measure Data
Hide Analysis Population Description
Changes from Baseline in Treg lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 0 0 0
No data displayed because Outcome Measure has zero total analyzed.
55.Secondary Outcome
Title Changes From Baseline in Serum Neurofilament
Hide Description The percentage change from Baseline in serum neurofilament was calculated.
Time Frame At Week 6 and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Safety data set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Median (95% Confidence Interval)
Unit of Measure: percent change
Week 6 Number Analyzed 71 participants 69 participants 69 participants
-4.0
(-10.0 to 8.0)
-1.0
(-12.0 to 8.0)
8.0
(-5.0 to 15.0)
Week 24 Number Analyzed 67 participants 64 participants 64 participants
-17.0
(-24.0 to -7.0)
-20.5
(-29.0 to -13.0)
6.5
(-11.0 to 25.0)
56.Secondary Outcome
Title Treatment Satisfaction Questionnaire for Medication (TSQM)
Hide Description

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).

Time Frame 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
Hide Outcome Measure Data
Hide Analysis Population Description
Safety analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:
During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
Overall Number of Participants Analyzed 71 69 69
Mean (Standard Deviation)
Unit of Measure: score
Effectiveness at Week 6 Number Analyzed 71 participants 69 participants 69 participants
62.45  (16.73) 67.16  (15.44) 60.55  (15.66)
Effectiveness at Week 24 Number Analyzed 69 participants 65 participants 64 participants
66.43  (14.61) 71.28  (17.58) 61.72  (15.27)
Side effects at Week 6 Number Analyzed 71 participants 69 participants 69 participants
92.70  (16.53) 96.02  (12.21) 95.29  (13.65)
Side effects at Week 24 Number Analyzed 69 participants 65 participants 64 participants
97.10  (9.37) 97.41  (11.25) 95.41  (12.99)
Convenience at Week 6 Number Analyzed 71 participants 69 participants 69 participants
82.62  (13.03) 81.48  (15.40) 80.59  (13.98)
Convenience at Week 24 Number Analyzed 69 participants 65 participants 64 participants
82.12  (12.55) 84.18  (14.66) 79.69  (13.13)
Global satisfaction at Week 6 Number Analyzed 71 participants 69 participants 69 participants
67.30  (18.34) 70.29  (15.34) 63.87  (16.93)
Global satisfaction at Week 24 Number Analyzed 69 participants 65 participants 64 participants
70.07  (16.13) 75.05  (17.87) 66.29  (15.04)
57.Secondary Outcome
Title 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.
Hide Description 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.
Time Frame Baseline, Week 6, Week 12, Week 18, and Week 24
Hide Outcome Measure Data
Hide Analysis Population Description
Full analysis set
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description:

During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (consisting of 2 tablets of 15 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium [IM90838]).

All patients received half the assigned dose during the first 7 days of the main treatment period (1 tablet per day) and then started taking the full assigned dose from Day 7 onwards (2 tablets once daily).

During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo.

All patients received 1 tablet per day during the first 7 days of the main treatment period and then started taking 2 tablets once daily from Day 7 onwards.

Overall Number of Participants Analyzed 71 69 69
Mean (Standard Deviation)
Unit of Measure: Percent change
NA [1]   (NA) NA [1]   (NA) NA [1]   (NA)
[1]
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.
Time Frame Main treatment period (24 weeks)
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Hide Arm/Group Description During the main treatment period (24 weeks), patients received once-daily oral doses of 30 mg IMU-838 (2 tablets of 15 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days. During the main treatment period (24 weeks), patients received once-daily oral doses of 45 mg IMU-838 consisting of 2 tablets of 22.5 mg vidofludimus calcium, IM90838) with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days. During the main treatment period (24 weeks), patients received once-daily oral doses of 2 tablets of placebo with an initiation dosing scheme of half the dose (1 tablet per day) during the first 7 days.
All-Cause Mortality
IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/71 (0.00%)      0/69 (0.00%)      0/69 (0.00%)    
Hide Serious Adverse Events
IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/71 (2.82%)      0/69 (0.00%)      1/69 (1.45%)    
Injury, poisoning and procedural complications       
Open fracture * 1  1/71 (1.41%)  1 0/69 (0.00%)  0 0/69 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Squamous cell carcinoma of the cervix * 1  0/71 (0.00%)  0 0/69 (0.00%)  0 1/69 (1.45%)  1
Renal and urinary disorders       
Hydronephrosis * 1  1/71 (1.41%)  1 0/69 (0.00%)  0 0/69 (0.00%)  0
Ureterolithiasis * 1  1/71 (1.41%)  1 0/69 (0.00%)  0 0/69 (0.00%)  0
1
Term from vocabulary, MedDRA Version 22.0
*
Indicates events were collected by non-systematic assessment
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
IMU-838 (30 mg/Day) IMU-838 (45 mg/Day) Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/71 (8.45%)      7/69 (10.14%)      7/69 (10.14%)    
Infections and infestations       
Nasopharyngitis * 1  3/71 (4.23%)  5 5/69 (7.25%)  7 3/69 (4.35%)  4
Nervous system disorders       
Headache * 1  3/71 (4.23%)  3 4/69 (5.80%)  5 4/69 (5.80%)  4
1
Term from vocabulary, MedDRA Version 22.0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Andreas Muehler, MD
Organization: Immunic AG
Phone: +4917678738359
EMail: andreas.muehler@imux.com
Layout table for additonal information
Responsible Party: Immunic AG
ClinicalTrials.gov Identifier: NCT03846219    
Other Study ID Numbers: P2-IMU-838-MS
2018-001896-19 ( EudraCT Number )
First Submitted: January 21, 2019
First Posted: February 19, 2019
Results First Submitted: April 28, 2021
Results First Posted: July 23, 2021
Last Update Posted: February 11, 2022