Trial Outcomes & Findings for Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple Sclerosis (NCT NCT01093326)

Last Updated: 2025-03-30

Results Overview

ARR is defined as the number of confirmed relapses per year. A relapse is defined as the occurrence of an acute episode of one or more new symptoms, or worsening of existing symptoms of multiple sclerosis (MS), not associated with fever or infection, and lasting for at least 24 hours after a stable period of at least 30 days. A confirmed relapse is a relapse accompanied by an increase from the previous clinically stable assessment (that is, performed at least 30 days after the onset of any previous relapse) of at least 0.5 point in the Expanded Disability Status Scale (EDSS) score, or one point in the score for at least one of the Functional System (FS) scores, excluding the bowel and bladder, and mental FS. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10 (death due to MS).

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

353 participants

Primary outcome timeframe

From ponesimod start date up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Results posted on

2025-03-30

Participant Flow

Participants who were enrolled in the core study (NCT01006265) entered this extension study. As planned, combined analysis (core plus extension study) was done for efficacy and safety (435 participants).

Data reported in each arm are based on first dose received during treatment period (TP) 1.

Participant milestones

Participant milestones
Measure	Ponesimod 10 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 20 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Overall Study STARTED	115	121	117
Overall Study COMPLETED	71	80	76
Overall Study NOT COMPLETED	44	41	41

Reasons for withdrawal

Reasons for withdrawal
Measure	Ponesimod 10 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 20 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Overall Study Death	0	1	0
Overall Study Lack of Efficacy	7	6	3
Overall Study Lost to Follow-up	2	5	4
Overall Study Physician Decision	3	1	3
Overall Study Withdrawal by Subject	30	27	26
Overall Study Adverse Event	2	1	4
Overall Study Other	0	0	1

Baseline Characteristics

Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple Sclerosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Ponesimod 10 Milligrams (mg) n=115 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 20 Milligrams (mg) n=121 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) n=117 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Total n=353 Participants Total of all reporting groups
Sex: Female, Male Male	38 Participants n=93 Participants	41 Participants n=4 Participants	41 Participants n=27 Participants	120 Participants n=483 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	115 Participants n=93 Participants	121 Participants n=4 Participants	117 Participants n=27 Participants	353 Participants n=483 Participants
Age, Categorical >=65 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Continuous	36.6 years STANDARD_DEVIATION 8.67 • n=93 Participants	36.1 years STANDARD_DEVIATION 8.58 • n=4 Participants	35.9 years STANDARD_DEVIATION 8.61 • n=27 Participants	36.2 years STANDARD_DEVIATION 8.6 • n=483 Participants
Sex: Female, Male Female	77 Participants n=93 Participants	80 Participants n=4 Participants	76 Participants n=27 Participants	233 Participants n=483 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	115 Participants n=93 Participants	121 Participants n=4 Participants	115 Participants n=27 Participants	351 Participants n=483 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants	1 Participants n=483 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Black or African American	3 Participants n=93 Participants	2 Participants n=4 Participants	4 Participants n=27 Participants	9 Participants n=483 Participants
Race (NIH/OMB) White	112 Participants n=93 Participants	118 Participants n=4 Participants	110 Participants n=27 Participants	340 Participants n=483 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants	0 Participants n=4 Participants	2 Participants n=27 Participants	2 Participants n=483 Participants
Region of Enrollment Austria	4 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	8 Participants n=483 Participants
Region of Enrollment Bulgaria	5 Participants n=93 Participants	3 Participants n=4 Participants	5 Participants n=27 Participants	13 Participants n=483 Participants
Region of Enrollment Canada	2 Participants n=93 Participants	2 Participants n=4 Participants	2 Participants n=27 Participants	6 Participants n=483 Participants
Region of Enrollment Czech Republic	12 Participants n=93 Participants	17 Participants n=4 Participants	14 Participants n=27 Participants	43 Participants n=483 Participants
Region of Enrollment Finland	6 Participants n=93 Participants	6 Participants n=4 Participants	4 Participants n=27 Participants	16 Participants n=483 Participants
Region of Enrollment France	1 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment Germany	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants	4 Participants n=483 Participants
Region of Enrollment Hungary	2 Participants n=93 Participants	8 Participants n=4 Participants	5 Participants n=27 Participants	15 Participants n=483 Participants
Region of Enrollment Israel	0 Participants n=93 Participants	2 Participants n=4 Participants	1 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment Italy	8 Participants n=93 Participants	8 Participants n=4 Participants	6 Participants n=27 Participants	22 Participants n=483 Participants
Region of Enrollment Netherlands	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants	2 Participants n=483 Participants
Region of Enrollment Poland	14 Participants n=93 Participants	6 Participants n=4 Participants	11 Participants n=27 Participants	31 Participants n=483 Participants
Region of Enrollment Romania	1 Participants n=93 Participants	2 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment Russia	8 Participants n=93 Participants	11 Participants n=4 Participants	11 Participants n=27 Participants	30 Participants n=483 Participants
Region of Enrollment Serbia	16 Participants n=93 Participants	13 Participants n=4 Participants	11 Participants n=27 Participants	40 Participants n=483 Participants
Region of Enrollment Spain	1 Participants n=93 Participants	4 Participants n=4 Participants	4 Participants n=27 Participants	9 Participants n=483 Participants
Region of Enrollment Sweden	4 Participants n=93 Participants	6 Participants n=4 Participants	8 Participants n=27 Participants	18 Participants n=483 Participants
Region of Enrollment Switzerland	2 Participants n=93 Participants	1 Participants n=4 Participants	0 Participants n=27 Participants	3 Participants n=483 Participants
Region of Enrollment Ukraine	4 Participants n=93 Participants	7 Participants n=4 Participants	5 Participants n=27 Participants	16 Participants n=483 Participants
Region of Enrollment United Kingdom	5 Participants n=93 Participants	4 Participants n=4 Participants	5 Participants n=27 Participants	14 Participants n=483 Participants
Region of Enrollment United States	19 Participants n=93 Participants	16 Participants n=4 Participants	19 Participants n=27 Participants	54 Participants n=483 Participants

PRIMARY outcome

Timeframe: From ponesimod start date up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Population: Ponesimod analysis set (PAS) included all participants who received at least one dose of ponesimod at any time during the core and/or the extension study (435 participants).

Outcome measures

Outcome measures
Measure	Ponesimod 20 Milligrams (mg) n=145 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) n=151 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 10 Milligrams (mg) n=139 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Annualized Relapse Rate (ARR) of Confirmed Relapses	0.142 Confirmed relapses per year Interval 0.102 to 0.198	0.150 Confirmed relapses per year Interval 0.105 to 0.215	0.205 Confirmed relapses per year Interval 0.15 to 0.282

PRIMARY outcome

Timeframe: From ponesimod start date up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Population: PAS included all participants who received at least one dose of ponesimod at any time during the core and/or the extension study (435 participants).

Time to first confirmed relapse was reported. A relapse is defined as the occurrence of an acute episode of one or more new symptoms, or worsening of existing symptoms of multiple sclerosis (MS), not associated with fever or infection, and lasting for at least 24 hours after a stable period of at least 30 days. A confirmed relapse is a relapse accompanied by an increase from the previous clinically stable assessment (that is, performed at least 30 days after the onset of any previous relapse) of at least 0.5 point in the Expanded Disability Status Scale (EDSS) score, or one point in the score for at least one of the Functional System (FS) scores, excluding the bowel and bladder, and mental FS. EDSS is ordinal clinical scale ranges from 0 (normal neurological examination) to 10 (death due to MS).

Outcome measures

Outcome measures
Measure	Ponesimod 20 Milligrams (mg) n=145 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) n=151 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 10 Milligrams (mg) n=139 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Time to First Confirmed Relapse	656.7 Weeks Interval 278.0 to NA indicates data for upper limit of 95% CI was not estimable due to less number of participants with event.	431.7 Weeks Interval 296.3 to NA indicates data for lower upper of 95% CI was not estimable due to less number of participants with event.	272.3 Weeks Interval 164.6 to NA indicates data for upper limit of 95% CI was not estimable due to less number of participants with event.

PRIMARY outcome

Timeframe: From ponesimod baseline up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Population: PAS included all participants who received at least one dose of ponesimod at any time during the core and/or the extension study (435 participants).

Time to 24 weeks confirmed disability progression (accumulation) was reported. Disability progression is defined as an increase of at least 1 point in the EDSS score if baseline EDSS was between 1 and 5.0, an increase of at least 1.5 points if baseline EDSS was 0, or an increase of at least 0.5 points if the baseline EDSS was equal or greater than 5.5. A 24-week confirmed disability progression is defined as a 24-week sustained increase from baseline in the EDSS scores, that is, every EDSS score (scheduled or unscheduled, with or without relapse) within a 24-week duration after the first progression should meet the progression criteria as specified above. EDSS is ordinal clinical scale ranges from 0 (normal neurological examination) to 10 (death due to MS).

Outcome measures

Outcome measures
Measure	Ponesimod 20 Milligrams (mg) n=145 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) n=151 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 10 Milligrams (mg) n=139 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Time to 24 Weeks Confirmed Disability Progression	NA Weeks NA indicates data for median, upper, and lower limit of 95% CI was not estimable due to less number of participants with event.	NA Weeks NA indicates data for median, upper, and lower limit of 95% CI was not estimable due to less number of participants with event.	NA Weeks Interval 470.3 to NA indicates data for median and upper limit of 95% CI was not estimable due to less number of participants with event.

OTHER_PRE_SPECIFIED outcome

Timeframe: From ponesimod start date up to the end of study treatment + 15 Days. The actual time of observation varied for each participant and could be up to 12.97 years + 15 days

Population: Ponesimod analysis set included all participants who received at least one dose of ponesimod at any time during the core and/or the extension study (435 participants).

Number of participants with at least one treatment-emergent SAEs were reported. An adverse event (AE) is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/biological agent under study. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalisation; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly/birth defect; suspected transmission of any infectious agent via a medicinal product or medically important. Treatment-emergent SAEs were those SAEs that occurred at or after the initial administration of ponesimod up to 15 days (inclusive) after last administration of ponesimod as study drug.

Outcome measures

Outcome measures
Measure	Ponesimod 20 Milligrams (mg) n=145 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 20 mg or placebo, entered this extension study and received ponesimod 20 mg capsules orally once daily during TP1. Participants continued to receive ponesimod 20 mg tablet orally, once daily during TP2 and TP3.	Ponesimod 40 Milligrams (mg) n=151 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 40 mg or placebo, entered this extension study and received ponesimod 40 mg capsules orally once daily during TP1. Participants were then re-randomized to receive ponesimod 10 or 20 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.	Ponesimod 10 Milligrams (mg) n=139 Participants Participants with relapsing-remitting multiple sclerosis having completed their regular Week 24 treatment visit of the core study (NCT01006265) while receiving ponesimod 10 mg or placebo, entered this extension study and received ponesimod 10 mg capsules orally once daily during treatment period (TP) 1. Participants continued to receive ponesimod 10 mg tablet orally, once daily during TP2. All participants received ponesimod 20 mg tablet orally, once daily during TP3.
Number of Participants With at Least One Treatment-emergent Serious Adverse Events (SAEs)	35 Participants	25 Participants	32 Participants

Adverse Events

Ponesimod 10 Milligrams (mg)

Serious events: 32 serious events

Other events: 121 other events

Deaths: 0 deaths

Ponesimod 20 Milligrams (mg)

Serious events: 35 serious events

Other events: 125 other events

Deaths: 1 deaths

Ponesimod 40 Milligrams (mg)

Serious events: 25 serious events

Other events: 140 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director Clinical Leader Neuroscience

Actelion Pharmaceuticals Ltd

Phone: 844-434-4210

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent application.
Publication restrictions are in place

Restriction type: OTHER