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

• 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: Immunic AG
• 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

Participant Flow

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
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

Baseline Characteristics

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo	Total
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
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

Outcome Measures

1. Primary Outcome

Title	Difference Between 45 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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
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)

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
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

Outcome Measure Data

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)
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Patients with observations at Week 24

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Patients with observations at Week 24.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Patients with observations in this analysis.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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: 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; Absence of fever or known infection (i.e. temperature [axillary, oral, or intra-auricular] ≤37.5ºC); 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)

Outcome Measure Data

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)
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
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)

Outcome Measure Data

Analysis Population Description

Patients analyzed

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo	IMU-838 Combined
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
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)

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Patients with observations.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)
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
Description	The number of patients experiencing treatment-emergent adverse events during the main treatment period was assessed.
Time Frame	Up to 24 weeks

Outcome Measure Data

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
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
Description	The number of patients experiencing serious adverse events during the main treatment period was assessed.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Safety data set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
Description	The number of patients diagnosed with hematuria during the main treatment period were assessed.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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:
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Patients with observations.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Patients with observations.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Patients with observations

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Patients with observations

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Patients with observations

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Patients with observations.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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)

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
Description	The time to treatment discontinuation up to Week 24 for any reason was determined.
Time Frame	Up to 24 weeks

Outcome Measure Data

Analysis Population Description

Patients with observations

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
Description	The discontinuation rate during the main treatment period was assessed.
Time Frame	at Week 24

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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)

Outcome Measure Data

Analysis Population Description

Data have not yet been analyzed.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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)

Outcome Measure Data

Analysis Population Description

Data have not yet been analyzed.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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)

Outcome Measure Data

Analysis Population Description

Data have not yet been analyzed.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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)

Outcome Measure Data

Analysis Population Description

Data have not yet been analyzed.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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)

Outcome Measure Data

Analysis Population Description

Data have not yet been analyzed.

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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
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

Outcome Measure Data

Analysis Population Description

Safety set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
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)

Outcome Measure Data

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
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
Description	The percentage change from Baseline in serum neurofilament was calculated.
Time Frame	At Week 6 and Week 24

Outcome Measure Data

Analysis Population Description

Safety data set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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)
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

Outcome Measure Data

Analysis Population Description

Safety analysis set

Arm/Group Title		IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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.
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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	IMU-838 (30 mg/Day)	IMU-838 (45 mg/Day)	Placebo
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.

Adverse Events

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
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%)
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
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

Limitations and Caveats

[Not Specified]

More Information

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

• Name/Title: Andreas Muehler, MD
• Organization: Immunic AG
• Phone: +4917678738359
• EMail: andreas.muehler@imux.com

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Fox RJ, Wiendl H, Wolf C, De Stefano N, Sellner J, Gryb V, Rejdak K, Bozhinov PS, Tomakh N, Skrypchenko I, Muehler AR. A double-blind, randomized, placebo-controlled phase 2 trial evaluating the selective dihydroorotate dehydrogenase inhibitor vidofludimus calcium in relapsing-remitting multiple sclerosis. Ann Clin Transl Neurol. 2022 Jul;9(7):977-987. doi: 10.1002/acn3.51574. Epub 2022 Jun 14.

• 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