Trial Outcomes & Findings for MRI Trial to exPlore the efficAcy and Safety of IMU-838 in Relapsing Remitting Multiple Sclerosis (EMPhASIS) (NCT NCT03846219)

NCT ID: NCT03846219

Last Updated: 2024-04-24

Results Overview

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).

• Recruitment status: ACTIVE_NOT_RECRUITING
• Study phase: PHASE2
• Target enrollment: 210 participants
• Primary outcome timeframe: Up to Week 24
• Results posted on: 2024-04-24

Participant Flow

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.

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.

Participant milestones

Measure	IMU-838 (30 mg/Day) 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.	IMU-838 (45 mg/Day) 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.	Placebo 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 Study STARTED	72	69	69
Overall Study Patients Treated	71	69	69
Overall Study COMPLETED	69	65	64
Overall Study NOT COMPLETED	3	4	5

Reasons for withdrawal

Measure	IMU-838 (30 mg/Day) 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.	IMU-838 (45 mg/Day) 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.	Placebo 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 Study Withdrawal by Subject	3	2	2
Overall Study Fulfilled hepatoxicity-related stopping rules	0	2	1
Overall Study Physician Decision	0	0	2

Baseline Characteristics

Full analysis set (FAS, the FAS consisted of all randomized patients who received at least 1 dose of the investigational medicinal product).

Baseline characteristics by cohort

Measure	IMU-838 (30 mg/Day) n=72 Participants 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).	IMU-838 (45 mg/Day) n=69 Participants 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).	Placebo n=69 Participants 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 n=210 Participants Total of all reporting groups
Age, Continuous	38.0 years n=71 Participants • Full analysis set (FAS, the FAS consisted of all randomized patients who received at least 1 dose of the investigational medicinal product).	36.0 years n=69 Participants • Full analysis set (FAS, the FAS consisted of all randomized patients who received at least 1 dose of the investigational medicinal product).	37.0 years n=69 Participants • Full analysis set (FAS, the FAS consisted of all randomized patients who received at least 1 dose of the investigational medicinal product).	36.0 years n=209 Participants • 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 Female	40 Participants n=71 Participants • Full analysis set	50 Participants n=69 Participants • Full analysis set	46 Participants n=69 Participants • Full analysis set	136 Participants n=209 Participants • Full analysis set
Sex: Female, Male Male	31 Participants n=71 Participants • Full analysis set	19 Participants n=69 Participants • Full analysis set	23 Participants n=69 Participants • Full analysis set	73 Participants n=209 Participants • Full analysis set
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Ethnicity (NIH/OMB) Not Hispanic or Latino	71 Participants n=71 Participants • Full analysis set	69 Participants n=69 Participants • Full analysis set	69 Participants n=69 Participants • Full analysis set	209 Participants n=209 Participants • Full analysis set
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) Asian	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) Black or African American	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) White	71 Participants n=71 Participants • Full analysis set	69 Participants n=69 Participants • Full analysis set	69 Participants n=69 Participants • Full analysis set	209 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) More than one race	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=71 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=69 Participants • Full analysis set	0 Participants n=209 Participants • Full analysis set
Region of Enrollment Romania	3 participants n=72 Participants • Patients randomized	2 participants n=69 Participants • Patients randomized	1 participants n=69 Participants • Patients randomized	6 participants n=210 Participants • Patients randomized
Region of Enrollment Ukraine	40 participants n=72 Participants • Patients randomized	36 participants n=69 Participants • Patients randomized	42 participants n=69 Participants • Patients randomized	118 participants n=210 Participants • Patients randomized
Region of Enrollment Poland	11 participants n=72 Participants • Patients randomized	6 participants n=69 Participants • Patients randomized	9 participants n=69 Participants • Patients randomized	26 participants n=210 Participants • Patients randomized
Region of Enrollment Bulgaria	18 participants n=72 Participants • Patients randomized	25 participants n=69 Participants • Patients randomized	17 participants n=69 Participants • Patients randomized	60 participants n=210 Participants • Patients randomized
Body mass index	23.491 kg/m^2 STANDARD_DEVIATION 5.311 • n=71 Participants • Full analysis set	24.786 kg/m^2 STANDARD_DEVIATION 5.067 • n=69 Participants • Full analysis set	24.462 kg/m^2 STANDARD_DEVIATION 4.758 • n=69 Participants • Full analysis set	24.239 kg/m^2 STANDARD_DEVIATION 5.059 • n=209 Participants • Full analysis set
Expanded Disability Status Scale	2.65 units on a scale STANDARD_DEVIATION 0.83 • n=71 Participants • Full analysis set	2.56 units on a scale STANDARD_DEVIATION 0.96 • n=69 Participants • Full analysis set	2.73 units on a scale STANDARD_DEVIATION 0.90 • n=69 Participants • Full analysis set	2.65 units on a scale STANDARD_DEVIATION 0.90 • n=209 Participants • Full analysis set
Gadolinium enhancing (Gd+) lesions	1.4 lesions STANDARD_DEVIATION 2.4 • n=71 Participants • Full analysis set	0.9 lesions STANDARD_DEVIATION 1.3 • n=69 Participants • Full analysis set	1.2 lesions STANDARD_DEVIATION 2.1 • n=69 Participants • Full analysis set	1.2 lesions STANDARD_DEVIATION 2.0 • n=209 Participants • Full analysis set
T2 lesion load	13.341 cm^3 STANDARD_DEVIATION 15.079 • n=71 Participants • Full analysis set	13.918 cm^3 STANDARD_DEVIATION 12.946 • n=69 Participants • Full analysis set	11.980 cm^3 STANDARD_DEVIATION 10.417 • n=69 Participants • Full analysis set	13.082 cm^3 STANDARD_DEVIATION 12.940 • n=209 Participants • Full analysis set
MRI field strength 1.5 Tesla	65 Participants n=71 Participants • Full analysis set	66 Participants n=69 Participants • Full analysis set	67 Participants n=69 Participants • Full analysis set	198 Participants n=209 Participants • Full analysis set
MRI field strength 3.0 Tesla	6 Participants n=71 Participants • Full analysis set	3 Participants n=69 Participants • Full analysis set	2 Participants n=69 Participants • Full analysis set	11 Participants n=209 Participants • Full analysis set
Duration of disease <=4 years	37 Participants n=71 Participants • Full analysis set	37 Participants n=69 Participants • Full analysis set	37 Participants n=69 Participants • Full analysis set	111 Participants n=209 Participants • Full analysis set
Duration of disease >4 years	34 Participants n=71 Participants • Full analysis set	32 Participants n=69 Participants • Full analysis set	32 Participants n=69 Participants • Full analysis set	98 Participants n=209 Participants • Full analysis set

PRIMARY outcome

Timeframe: Up to Week 24

Population: FAS consisting of all randomized patients who received at least 1 dose of the investigational medicinal product (IMP).

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).

Outcome measures

Measure	IMU-838 (45 mg/Day) n=69 Participants 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.	Placebo n=69 Participants 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.	Placebo 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Difference Between 45 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	2.4 CUA MRI lesions Interval 1.1 to 4.9	6.3 CUA MRI lesions Interval 2.8 to 13.9	—	—	—

SECONDARY outcome

Timeframe: Up to Week 24

Population: FAS consisting of all randomized patients who received at least 1 dose of the IMP.

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).

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Difference Between 30 mg/Day IMU-838 and Placebo in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	4.0 CUA MRI lesions Interval 2.2 to 7.2	13.2 CUA MRI lesions Interval 6.6 to 26.4	—	—	—

SECONDARY outcome

Timeframe: At Week 24

Population: FAS consisting of all randomized patients who received at least 1 dose of the investigational medicinal product.

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).

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Difference Between 45 mg/Day IMU-838 and 30 mg/Day IMU-838 in the Cumulative Number of Combined Unique Active (CUA) MRI Lesions	4.2 CUA MRI lesions Interval 2.5 to 7.1	4.4 CUA MRI lesions Interval 2.4 to 8.1	—	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	1.1 CUA MRI lesions Interval 0.5 to 2.1	0.8 CUA MRI lesions Interval 0.4 to 1.8	3.2 CUA MRI lesions Interval 1.5 to 6.6	—	—
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 Week 12	1.3 CUA MRI lesions Interval 0.7 to 2.3	1.2 CUA MRI lesions Interval 0.6 to 2.6	3.4 CUA MRI lesions Interval 1.7 to 7.0	—	—
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 Week 18	1.3 CUA MRI lesions Interval 0.7 to 2.5	0.8 CUA MRI lesions Interval 0.3 to 1.7	3.2 CUA MRI lesions Interval 1.5 to 6.6	—	—
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 Week 24	1.6 CUA MRI lesions Interval 0.8 to 3.5	1.6 CUA MRI lesions Interval 0.6 to 4.4	3.7 CUA MRI lesions Interval 1.5 to 9.3	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 18)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	0.8 CUA MRI lesions Interval 0.4 to 1.7	0.6 CUA MRI lesions Interval 0.3 to 1.4	2.5 CUA MRI lesions Interval 1.1 to 5.5	—	—
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 Week 12	1.7 CUA MRI lesions Interval 1.0 to 3.0	1.6 CUA MRI lesions Interval 0.9 to 3.2	5.3 CUA MRI lesions Interval 2.8 to 10.0	—	—
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 Week 18	2.7 CUA MRI lesions Interval 1.6 to 4.5	2.5 CUA MRI lesions Interval 1.4 to 4.6	8.0 CUA MRI lesions Interval 4.5 to 14.4	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: This measure was not analyzed because it was determined to be redundant with Outcome Measure 7. No data are available to be reported.

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".

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T2 lesion load was calculated.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	2.2 % change from Baseline Interval -0.4 to 3.0	1.7 % change from Baseline Interval 0.3 to 3.6	2.4 % change from Baseline Interval 0.9 to 4.5	—	—
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 Week 12	3.3 % change from Baseline Interval 2.2 to 4.9	3.4 % change from Baseline Interval 2.2 to 5.1	4.7 % change from Baseline Interval 1.8 to 6.6	—	—
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 Week 18	4.9 % change from Baseline Interval 2.3 to 7.3	4.6 % change from Baseline Interval 3.4 to 6.2	7.1 % change from Baseline Interval 4.8 to 8.9	—	—
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 Week 24	6.6 % change from Baseline Interval 3.5 to 9.7	7.3 % change from Baseline Interval 4.2 to 8.7	9.0 % change from Baseline Interval 7.1 to 12.0	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

MRI scans were assessed centrally and adhered to a standardized MRI protocol. The percentage change from Baseline in T1 lesion load was calculated.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	-2.9 % change from Baseline Interval -4.9 to -0.9	-0.4 % change from Baseline Interval -3.3 to 0.8	-4.2 % change from Baseline Interval -5.7 to -1.2	—	—
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 Week 12	-4.0 % change from Baseline Interval -5.7 to -1.4	-1.6 % change from Baseline Interval -4.1 to 0.0	0.0 % change from Baseline Interval -2.0 to 0.8	—	—
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 Week 18	-3.8 % change from Baseline Interval -5.6 to -1.4	-1.4 % change from Baseline Interval -3.8 to 1.8	-0.7 % change from Baseline Interval -2.1 to 1.0	—	—
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 Week 24	-5.7 % change from Baseline Interval -7.6 to -1.7	-0.9 % change from Baseline Interval -3.6 to 0.0	-0.8 % change from Baseline Interval -2.3 to 0.7	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	1.0 Gd+ lesions Interval 0.5 to 2.0	0.8 Gd+ lesions Interval 0.3 to 1.7	2.8 Gd+ lesions Interval 1.3 to 6.2	—	—
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 Week 12	2.1 Gd+ lesions Interval 1.2 to 3.7	1.7 Gd+ lesions Interval 0.9 to 3.3	6.2 Gd+ lesions Interval 3.2 to 11.9	—	—
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 Week 18	3.1 Gd+ lesions Interval 1.8 to 5.2	2.4 Gd+ lesions Interval 1.3 to 4.5	9.1 Gd+ lesions Interval 4.9 to 16.8	—	—
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 Week 24	4.5 Gd+ lesions Interval 2.7 to 7.7	4.0 Gd+ lesions Interval 2.1 to 7.8	13.0 Gd+ lesions Interval 6.8 to 24.5	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	0.8 T2 lesions Interval 0.4 to 1.7	0.7 T2 lesions Interval 0.3 to 1.5	2.6 T2 lesions Interval 1.2 to 5.8	—	—
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 Week 12	1.8 T2 lesions Interval 1.1 to 3.1	1.8 T2 lesions Interval 1.0 to 3.5	6.0 T2 lesions Interval 3.2 to 11.2	—	—
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 Week 18	2.8 T2 lesions Interval 1.7 to 4.5	2.7 T2 lesions Interval 1.5 to 4.9	8.8 T2 lesions Interval 5.0 to 15.5	—	—
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 Week 24	4.1 T2 lesions Interval 2.5 to 6.6	4.2 T2 lesions Interval 2.3 to 7.7	11.9 T2 lesions Interval 6.7 to 21.1	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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 Week 6	0.3 T1 lesions Interval 0.1 to 0.8	0.2 T1 lesions Interval 0.1 to 0.6	1.1 T1 lesions Interval 0.4 to 3.4	—	—
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 Week 12	0.6 T1 lesions Interval 0.3 to 1.2	0.6 T1 lesions Interval 0.3 to 1.3	2.5 T1 lesions Interval 1.1 to 5.6	—	—
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 Week 18	1.0 T1 lesions Interval 0.6 to 1.9	1.0 T1 lesions Interval 0.5 to 1.9	3.9 T1 lesions Interval 2.0 to 7.4	—	—
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 Week 24	1.4 T1 lesions Interval 0.8 to 2.4	1.5 T1 lesions Interval 0.8 to 2.9	4.7 T1 lesions Interval 2.5 to 8.8	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	42 Participants	34 Participants	26 Participants	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	36 Participants	29 Participants	22 Participants	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Patients with observations at Week 24

MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with CUA lesions at Week 24 was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=69 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	15 Participants	19 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Patients with observations at Week 24.

MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with Gd+ lesions at Week 24 was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=69 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	10 Participants	16 Participants	25 Participants	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Patients with observations in this analysis.

MRI scans were assessed centrally and adhered to a standardized MRI protocol. The number of patients with T2 lesions at Week 24 was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=69 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	15 Participants	18 Participants	21 Participants	—	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

The adjusted mean annualized relapse rate during the main treatment period was calculated. Estimates were adjusted for baseline number of Gd+ lesions (0, ≥1) using a Poisson model with a logarithmic link function. Log transformation of real exposure time of main treatment period was used as offset term.

All of the following criteria had to be met for a clinical event to qualify as a relapse:

1. Neurological deficit, either newly appearing or re-appearing, with abnormality specified by both neurological abnormality separated by at least 30 days from onset of a preceding relapse AND neurological abnormality lasting for at least 24 hours

2. Absence of fever or known infection (i.e. temperature [axillary, oral, or intra-auricular]

≤37.5ºC)

3. Neurological impairment, defined as either increase in at least one of the functional systems of the EDSS OR increase of the total EDSS score. In both cases, the increase in EDSS had to correlate with the patient's reported symptoms.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined n=140 Participants Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With IMU-838 Combined) n=69 Participants 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.
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)	0.39 relapses per person-years Interval 0.22 to 0.69	0.48 relapses per person-years Interval 0.28 to 0.82	0.53 relapses per person-years Interval 0.32 to 0.89	0.43 relapses per person-years Interval 0.29 to 0.62	0.54 relapses per person-years Interval 0.34 to 0.86

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Patients analyzed

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=70 Participants 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.	Placebo n=67 Participants 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.	Placebo n=67 Participants 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.	IMU-838 Combined n=137 Participants Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	60 Participants	54 Participants	51 Participants	114 Participants	—

SECONDARY outcome

Timeframe: Throughout the main treatment period (Day 0 - Week 24)

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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	NA days The median time to relapse could not be calculated.	NA days The median time to relapse could not be calculated.	NA days The median time to relapse could not be calculated.	—	—

SECONDARY outcome

Timeframe: Baseline, Week 12, and Week 24

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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) Week 12	-0.01 score on a scale Standard Deviation 0.28	0.00 score on a scale Standard Deviation 0.42	0.03 score on a scale Standard Deviation 0.38	—	—
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) Week 24	0.01 score on a scale Standard Deviation 0.25	0.00 score on a scale Standard Deviation 0.39	0.08 score on a scale Standard Deviation 0.39	—	—

SECONDARY outcome

Timeframe: Week 12 and Week 24

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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) Up to Week 12	6 Participants	7 Participants	9 Participants	—	—
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) Up to Week 24	8 Participants	8 Participants	15 Participants	—	—

SECONDARY outcome

Timeframe: At Week 24

Population: Patients with observations.

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=67 Participants 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.	Placebo n=64 Participants 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.	Placebo 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels 3rd quartile of IMU-838 trough level	4.4 CUA MRI lesions Standard Deviation 5.8	2.0 CUA MRI lesions Standard Deviation 2.2	—	—	—
Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels 1st quartile of IMU-838 trough level	1.1 CUA MRI lesions Standard Deviation 2.0	1.6 CUA MRI lesions Standard Deviation 3.1	—	—	—
Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels 2nd quartile of IMU-838 trough level	2.2 CUA MRI lesions Standard Deviation 4.9	1.8 CUA MRI lesions Standard Deviation 2.8	—	—	—
Correlation of MRI-based Assessments With Quartiles of IMU-838 Trough Levels 4th quartile of IMU-838 trough level	6.8 CUA MRI lesions Standard Deviation 14.7	5.3 CUA MRI lesions Standard Deviation 9.8	—	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set consisting of all randomized patients who received at least 1 dose of IMP.

The number of patients experiencing treatment-emergent adverse events during the main treatment period was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With AEs	32 Participants	28 Participants	30 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety data set

The number of patients experiencing serious adverse events during the main treatment period was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With Serious AEs	2 Participants	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Hepatic enzyme increased	1 Participants	2 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Anemia	0 Participants	0 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Iron deficiency anemia	0 Participants	0 Participants	2 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Leukopenia	0 Participants	0 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Neutropenia	0 Participants	0 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Alanine aminotransferase increased	1 Participants	0 Participants	2 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Aspartate aminotransferase increased	1 Participants	0 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Blood bilirubin increased	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Blood creatine phosphokinase increased	2 Participants	0 Participants	0 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Blood creatinine increased	1 Participants	0 Participants	0 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) C-reactive protein increased	0 Participants	1 Participants	0 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Lipase increased	0 Participants	0 Participants	1 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Transaminases increased	0 Participants	1 Participants	0 Participants	—	—
Number of Participants With Clinically Significant Laboratory Abnormalities (as Assessed by the Investigator) Hypertriglyceridemia	1 Participants	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With AEs of Special Interest: Red Blood Cell Urine Positive, at Least of Moderate Intensity	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

The number of patients diagnosed with hematuria during the main treatment period were assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With AEs of Special Interest: Hematuria	0 Participants	0 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

The number of patients diagnosed with retroperitoneal colicky pain with suspected or confirmed nephrolithiasis during the main treatment period were assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Number of Participants With AEs of Special Interest: Retroperitoneal Colicky Pain With Suspected or Confirmed Nephrolithiasis	1 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

• 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

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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: AST >1.5 x ULN AND representing a % change from Baseline ≥35%	1 Participants	3 Participants	4 Participants	—	—
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: Alopecia	3 Participants	1 Participants	0 Participants	—	—
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: Hemorrhage	0 Participants	0 Participants	0 Participants	—	—
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: ALT >1.5 x ULN AND representing a % change from Baseline ≥35%	2 Participants	4 Participants	5 Participants	—	—
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: GGT >1.5 x ULN AND representing a % change from Baseline ≥35%	3 Participants	2 Participants	1 Participants	—	—
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: Neutropenia	0 Participants	0 Participants	1 Participants	—	—
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: Lymphopenia	0 Participants	0 Participants	0 Participants	—	—
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: Diarrhea	0 Participants	0 Participants	0 Participants	—	—
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: Total bilirubin >1.5 x ULN AND representing a % change from Baseline ≥35%	0 Participants	0 Participants	0 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
12-lead Electrocardiogram (ECG): Heart Rate Screening 1	67.0 beats per minute Interval 45.0 to 100.0	68.0 beats per minute Interval 51.0 to 93.0	67.0 beats per minute Interval 46.0 to 97.0	—	—
12-lead Electrocardiogram (ECG): Heart Rate Week 24	69.5 beats per minute Interval 46.0 to 120.0	69.0 beats per minute Interval 43.0 to 116.0	70.0 beats per minute Interval 46.0 to 105.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
12-lead Electrocardiogram (ECG): PQ-interval Screening 1	147.0 msec Interval 95.0 to 448.0	140.0 msec Interval 87.0 to 200.0	150.0 msec Interval 95.0 to 200.0	—	—
12-lead Electrocardiogram (ECG): PQ-interval Week 24	146.5 msec Interval 77.0 to 247.0	146.0 msec Interval 100.0 to 213.0	150.5 msec Interval 92.0 to 202.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
12-lead Electrocardiogram (ECG): QRS-interval Screening 1	90.0 msec Interval 60.0 to 148.0	86.0 msec Interval 60.0 to 135.0	90.0 msec Interval 66.0 to 112.0	—	—
12-lead Electrocardiogram (ECG): QRS-interval Week 24	90.0 msec Interval 60.0 to 128.0	86.0 msec Interval 60.0 to 120.0	91.0 msec Interval 60.0 to 113.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
12-lead Electrocardiogram (ECG): QT-interval Screening 1	383.0 msec Interval 310.0 to 514.0	380.0 msec Interval 320.0 to 447.0	387.0 msec Interval 335.0 to 448.0	—	—
12-lead Electrocardiogram (ECG): QT-interval Week 24	376.5 msec Interval 71.0 to 472.0	374.5 msec Interval 286.0 to 472.0	385.0 msec Interval 310.0 to 448.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
12-lead Electrocardiogram (ECG): Heart Rate-corrected QTc Interval (According to Bazett's Formula) Screening 1	407.0 msec Interval 325.0 to 500.0	404.0 msec Interval 340.0 to 483.0	410.0 msec Interval 361.0 to 468.0	—	—
12-lead Electrocardiogram (ECG): Heart Rate-corrected QTc Interval (According to Bazett's Formula) Week 24	407.0 msec Interval 77.0 to 478.0	404.0 msec Interval 283.0 to 467.0	409.0 msec Interval 353.0 to 483.0	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Physical Examination	0 Participants	1 Participants	3 Participants	—	—

SECONDARY outcome

Timeframe: at Screening

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Height	170.0 cm Interval 154.0 to 198.0	167.0 cm Interval 154.0 to 188.0	168.0 cm Interval 149.0 to 192.0	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients with observations.

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=66 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Weight (Absolute Change From Baseline at Week 24)	0.00 kg Interval -18.2 to 8.6	0.00 kg Interval -7.0 to 7.5	0.00 kg Interval -11.0 to 12.5	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients with observations.

Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=67 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Body Temperature (ºC) (Absolute Change From Baseline at Week 24)	0.00 °C Interval -0.8 to 1.6	0.00 °C Interval -0.7 to 0.7	0.00 °C Interval -0.8 to 0.4	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients with observations

Changes in vital signs judged by the investigator as clinically significant were to be reported as an AE.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=67 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Respiratory Rate (Absolute Change From Baseline at Week 24)	0.0 breaths/min Interval -4.0 to 6.0	0.0 breaths/min Interval -6.0 to 4.0	0.0 breaths/min Interval -3.0 to 9.0	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients with observations

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=67 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Pulse Rates (Absolute Change From Baseline at Week 24)	0.0 beats per minute Interval -24.0 to 16.0	0.0 beats per minute Interval -30.0 to 24.0	-1.0 beats per minute Interval -18.0 to 22.0	—	—

SECONDARY outcome

Timeframe: Baseline and 24 weeks

Population: Patients with observations

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=67 Participants 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.	Placebo n=65 Participants 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.	Placebo n=64 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Vital Signs: Systolic and Diastolic Blood Pressures (Absolute Change From Baseline at Week 24) Systolic blood pressure	0.0 mmHg Interval -36.0 to 20.0	0.0 mmHg Interval -30.0 to 30.0	0.0 mmHg Interval -22.0 to 30.0	—	—
Vital Signs: Systolic and Diastolic Blood Pressures (Absolute Change From Baseline at Week 24) Diastolic blood pressure	0.0 mmHg Interval -25.0 to 22.0	0.0 mmHg Interval -20.0 to 30.0	0.0 mmHg Interval -26.0 to 20.0	—	—

SECONDARY outcome

Timeframe: Change from Baseline to 4 hours after first dose

Population: Patients with observations.

The fold change in miR-122 from pre dose to 4 hours post dose was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=69 Participants 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.	Placebo n=67 Participants 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.	Placebo n=67 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Micro Ribonucleic Acid (miR)-122 Expression	0.727 fold change Interval 0.12 to 63.23	0.991 fold change Interval 0.19 to 53.75	0.946 fold change Interval 0.12 to 50.11	—	—

SECONDARY outcome

Timeframe: At Screening Visit 1, at Week 24, and at EoS visit (EoS visit 30 days (+14 days) after last IMP intake)

Population: Safety analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine Screening 1	32 Participants	27 Participants	29 Participants	—	—
Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine Week 24	27 Participants	16 Participants	18 Participants	—	—
Presence of John Cunningham Virus (JCV) Deoxyribonucleic Acid (DNA) in Urine in Patients With Detectable JCV-DNA in Urine End-of-study	0 Participants	1 Participants	1 Participants	—	—

SECONDARY outcome

Timeframe: Up to 24 weeks

Population: Patients with observations

The time to treatment discontinuation up to Week 24 for any reason was determined.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=2 Participants 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.	Placebo n=4 Participants 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.	Placebo n=5 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Time to Treatment Discontinuation for Any Reason	106.5 days Interval 43.0 to 170.0	66.5 days Interval 47.0 to 178.0	98.0 days Interval 85.0 to 139.0	—	—

SECONDARY outcome

Timeframe: at Week 24

Population: Safety analysis set

The discontinuation rate during the main treatment period was assessed.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Rate of Treatment Discontinuations up to Week 24	2 Participants	4 Participants	5 Participants	—	—

SECONDARY outcome

Timeframe: At Week 6 (3-10 hours post-dose)

Population: Data have not yet been analyzed.

One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 6 (3-10 hours post-dose)

Population: Data have not yet been analyzed.

One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 6 (3-10 hours post-dose)

Population: Data have not yet been analyzed.

One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 6 (3-10 hours post-dose)

Population: Data have not yet been analyzed.

One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 6 (3-10 hours post-dose)

Population: Data have not yet been analyzed.

One single measurement between 3 and 10 hours post-dose. Population pharmacokinetics have not been reported yet.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Day 7 and Weeks 6, 12, 18, and 24

Population: Safety set

Plasma trough levels of IMU-838 were assessed at Day 7 and at Weeks 6, 12, 18, and 24.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Plasma Trough Levels of IMU-838 Day 7	2.155 μg/mL Interval 0.9 to 8.96	3.100 μg/mL Interval 0.12 to 7.89	—	—	—
Plasma Trough Levels of IMU-838 Week 6	4.320 μg/mL Interval 0.0 to 15.7	6.240 μg/mL Interval 0.0 to 18.3	—	—	—
Plasma Trough Levels of IMU-838 Week 12	4.160 μg/mL Interval 0.0 to 12.4	5.420 μg/mL Interval 0.0 to 14.0	—	—	—
Plasma Trough Levels of IMU-838 Week 18	4.165 μg/mL Interval 0.0 to 12.1	5.990 μg/mL Interval 0.0 to 15.0	—	—	—
Plasma Trough Levels of IMU-838 Week 24	4.010 μg/mL Interval 0.0 to 8.14	5.700 μg/mL Interval 0.0 to 16.3	—	—	—

SECONDARY outcome

Timeframe: At Weeks 6 and 24 (in selected Biomarker Centers only)

Population: Changes from Baseline in Th1 lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Weeks 6 and 24 (in selected Biomarker Centers only)

Population: Changes from Baseline in Th17 lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Weeks 6 and 24 (in selected Biomarker Centers only)

Population: Changes from Baseline in Treg lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Changes from Baseline in lymphocyte subsets were listed only; no descriptive statistics by treatment arm were calculated.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At Week 6 and Week 24

Population: Safety data set

The percentage change from Baseline in serum neurofilament was calculated.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Changes From Baseline in Serum Neurofilament Week 6	-4.0 percent change Interval -10.0 to 8.0	-1.0 percent change Interval -12.0 to 8.0	8.0 percent change Interval -5.0 to 15.0	—	—
Changes From Baseline in Serum Neurofilament Week 24	-17.0 percent change Interval -24.0 to -7.0	-20.5 percent change Interval -29.0 to -13.0	6.5 percent change Interval -11.0 to 25.0	—	—

SECONDARY outcome

Timeframe: assessed at 6 weeks, 24 weeks, and end of study visit (EoS visit 30 days [+14 days] after last IMP intake), reported at Week 6 and Week 24

Population: Safety analysis set

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).

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness at Week 6	62.45 score Standard Deviation 16.73	67.16 score Standard Deviation 15.44	60.55 score Standard Deviation 15.66	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Effectiveness at Week 24	66.43 score Standard Deviation 14.61	71.28 score Standard Deviation 17.58	61.72 score Standard Deviation 15.27	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Side effects at Week 6	92.70 score Standard Deviation 16.53	96.02 score Standard Deviation 12.21	95.29 score Standard Deviation 13.65	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Side effects at Week 24	97.10 score Standard Deviation 9.37	97.41 score Standard Deviation 11.25	95.41 score Standard Deviation 12.99	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience at Week 6	82.62 score Standard Deviation 13.03	81.48 score Standard Deviation 15.40	80.59 score Standard Deviation 13.98	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Convenience at Week 24	82.12 score Standard Deviation 12.55	84.18 score Standard Deviation 14.66	79.69 score Standard Deviation 13.13	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Global satisfaction at Week 6	67.30 score Standard Deviation 18.34	70.29 score Standard Deviation 15.34	63.87 score Standard Deviation 16.93	—	—
Treatment Satisfaction Questionnaire for Medication (TSQM) Global satisfaction at Week 24	70.07 score Standard Deviation 16.13	75.05 score Standard Deviation 17.87	66.29 score Standard Deviation 15.04	—	—

SECONDARY outcome

Timeframe: Baseline, Week 6, Week 12, Week 18, and Week 24

Population: Full analysis set

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.

Outcome measures

Measure	IMU-838 (45 mg/Day) n=71 Participants 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.	Placebo n=69 Participants 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.	Placebo n=69 Participants 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.	IMU-838 Combined Groups 30 mg IMU-838 and 45 mg IMU-838 combined	Placebo (Compared With 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.
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.	NA Percent change Standard Deviation NA 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.	NA Percent change Standard Deviation NA 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.	NA Percent change Standard Deviation NA 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

IMU-838 (30 mg/Day)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

IMU-838 (45 mg/Day)

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Placebo

Serious events: 1 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Measure	IMU-838 (30 mg/Day) n=71 participants at risk 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.	IMU-838 (45 mg/Day) n=69 participants at risk 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.	Placebo n=69 participants at risk 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.
Injury, poisoning and procedural complications Open fracture	1.4% 1/71 • Number of events 1 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Squamous cell carcinoma of the cervix	0.00% 0/71 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)	1.4% 1/69 • Number of events 1 • Main treatment period (24 weeks)
Renal and urinary disorders Hydronephrosis	1.4% 1/71 • Number of events 1 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)
Renal and urinary disorders Ureterolithiasis	1.4% 1/71 • Number of events 1 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)	0.00% 0/69 • Main treatment period (24 weeks)

Other adverse events

Measure	IMU-838 (30 mg/Day) n=71 participants at risk 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.	IMU-838 (45 mg/Day) n=69 participants at risk 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.	Placebo n=69 participants at risk 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.
Infections and infestations Nasopharyngitis	4.2% 3/71 • Number of events 5 • Main treatment period (24 weeks)	7.2% 5/69 • Number of events 7 • Main treatment period (24 weeks)	4.3% 3/69 • Number of events 4 • Main treatment period (24 weeks)
Nervous system disorders Headache	4.2% 3/71 • Number of events 3 • Main treatment period (24 weeks)	5.8% 4/69 • Number of events 5 • Main treatment period (24 weeks)	5.8% 4/69 • Number of events 4 • Main treatment period (24 weeks)

Additional Information

Andreas Muehler, MD

Immunic AG

Phone: +4917678738359

Email: andreas.muehler@imux.com

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60