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Multiple SclerosisPhase 3OPTIMUMNCT02425644

Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis

A Phase 3 study testing ponesimod and teriflunomide in people with Multiple Sclerosis, run by Actelion at 162 sites in 28 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

International clinical trial to compare ponesimod and teriflunomide in relapsing multiple sclerosis Read more about this study

Who is it for?
Ages 18 to 55 years
Conditions the study is for
Multiple Sclerosis
What is being tested?
ponesimod and teriflunomide
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,133 participants
Where
162 sitesin 28 countries
Study dates
4 Jun 2015to 16 May 2019
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Male and female subjects aged 18 to 55 years with established diagnosis of MS McDonald 2010 with relapsing course from onset (i.e., RRMS and SPMS with superimposed relapses).
  • Subjects must have active disease evidenced by one or more MS attacks with onset within the period of 12 to 1 months prior to randomization, or by two or more MS attacks with onset within the 24 to 1 months prior to randomization, or with one or more gadolinium-enhancing (Gd+) lesion(s) of the brain on an MRI performed within 6 months prior to randomization.
  • Enrolled subjects must be ambulatory (EDSS score of up to 5.5 inclusive) and may be treatment-naïve or previously treated with MS disease modifying therapy.

Who cannot join

  • Subjects with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic,ophthalmological conditions) or lactating or pregnant women are not eligible to enter the study.
  • Subjects with contraindications to MRI or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study are not eligible to enter the study.

Trial locations and contacts

162 sites in 28 countries.

162 sites in 28 countries

Russia28 sites

  • Investigator Site 3821

    Barnaul, Altayskiy Kray, 656024

  • Investigator Site 3818

    Belgorod, 308007

  • Investigator Site 3837

    Bryansk, 241033

  • Investigator Site 3811

    Kazan', 420029

  • Investigator Site 3822

    Kemerovo, 650066

  • Investigator Site 3814

    Krasnoyarsk, 660037

  • Investigator Site 3823

    Kursk, 305007

  • Investigator Site 3831

    Moscow, 119049

  • Investigator Site 3803

    Moscow, 127015

  • Investigator Site 3840

    Moscow, 127015

  • Investigator Site 3810

    Moscow, 129128

  • Investigator Site 3834

    Nizhny Novgorod, 603076

  • Investigator Site 3802

    Nizhny Novgorod, 603155

  • Investigator Site 3829

    Novosibirsk, 630007

  • Investigator Site 3839

    Perm, 614990

  • Investigator Site 3812

    Pyatigorsk, 357538

  • Investigator Site 3808

    Saint Petersburg, 194354

  • Investigator Site 3833

    Saint Petersburg, 197022

  • Investigator Site 3813

    Saint Petersburg, 197110

  • Investigator Site 3807

    Saint Petersburg, 197376

  • Investigator Site 3815

    Saint Petersburg, 197706

  • Investigator Site 3805

    Samara, 443095

  • Investigator Site 3825

    Smolensk, 214019

  • Investigator Site 3801

    Tomsk, 634050

  • Investigator Site 3819

    Tver', 170026

  • Investigator Site 3835

    Velikiy Novgorod, 173008

  • Investigator Site 3842

    Yaroslavl, 150030

  • Investigator Site 3836

    Yekaterinburg, 620102

Other trials in Russia

Ukraine15 sites

  • Investigator Site 3714

    Chernihiv, 14001

  • Investigator Site 3701

    Chernihiv, 14029

  • Investigator Site 3713

    Ivano-Frankivsk, 76008

  • Investigator Site 3711

    Ivano-Frankivsk, 76018

  • Investigator Site 3723

    Kharkiv, 61103

  • Investigator Site 3724

    Kharkiv, 61176

  • Investigator Site 3716

    Kyiv, 03115

  • Investigator Site 3715

    Lviv, 79000

  • Investigator Site 3721

    Lviv, 79010

  • Investigator Site 3703

    Odesa, 65009

  • Investigator Site 3717

    Poltava, 36011

  • Investigator Site 3730

    Ternopil, 46027

  • Investigator Site 3718

    Vinnytsia, 21005

  • Investigator Site 3722

    Zaporizhia, 69000

  • Investigator Site 3725

    Zhytomyr, 10008

Other trials in Ukraine

Poland12 sites

  • Investigator Site 3219

    Bialystok, 15-270

  • Investigator Site 3215

    Bydgoszcz, 85-795

  • Investigator Site 3208

    Gdansk, 80-803

  • Investigator Site 3217

    Katowice, 40-595

  • Investigator Site 3203

    Katowice, 40-752

  • Investigator Site 3205

    Konstancin-Jeziorna, 05-510

  • Investigator Site 3216

    Ksawerów, 95-054

  • Investigator Site 3220

    Lublin, 20-015

  • Investigator Site 3202

    Poznan, 60-355

  • Investigator Site 3214

    Poznan, 60-848

  • Investigator Site 3207

    Poznan, 61-853

  • Investigator Site 3213

    Wroclaw, 51-685

Other trials in Poland

United States10 sites

  • Investigator Site 8045

    Carlsbad, California, 92011

  • Investigator Site 8006

    Columbus, Ohio, 43214

  • Investigator Site 8036

    Denver, Colorado, 80209

  • Investigator Site 8015

    Franklin, Tennessee, 37064

  • Investigator Site 8013

    Indianapolis, Indiana, 46256

  • Investigator Site 8042

    Orem, Utah, 84058

  • Investigator Site 8065

    Ormond Beach, Florida, 32174

  • Investigator Site 8311

    Pomona, California, 91767

  • Investigator Site 8040

    Raleigh, North Carolina, 27607

  • Investigator Site 8018

    Tampa, Florida, 33612

Other trials in United States

Czechia9 sites

  • Investigator Site 3009

    Brno, 625 00

  • Investigator Site 3003

    Brno, 656 91

  • Investigator Site 3010

    Hradec Králové, 500 05

  • Investigator Site 3006

    Jihlava, 586 33

  • Investigator Site 3002

    Ostrava-Poruba, 708 52

  • Investigator Site 3007

    Pardubice, 532 03

  • Investigator Site 3001

    Prague, 128 08

  • Investigator Site 3008

    Prague, 150 06

  • Investigator Site 3004

    Teplice, 415 29

Other trials in Czechia

Bulgaria7 sites

  • Investigator Site 2709

    Plovdiv, 4002

  • Investigator Site 2711

    Sofia, 1113

  • Investigator Site 2702

    Sofia, 1309

  • Investigator Site 2707

    Sofia, 1407

  • Investigator Site 2701

    Sofia, 1431

  • Investigator Site 2708

    Sofia, 1431

  • Investigator Site 2703

    Sofia, 1606

Other trials in Bulgaria

Spain6 sites

  • Investigator Site 1509

    Barcelona, 08003

  • Investigator Site 1505

    Barcelona, 08035

  • Investigator Site 1504

    Barcelona, 08036

  • Investigator Site 1502

    Madrid, 28006

  • Investigator Site 1501

    Málaga, 29010

  • Investigator Site 1506

    Seville, 41009

Other trials in Spain

Belarus5 sites

  • Investigator Site 3605

    Grodno, 230017

  • Investigator Site 3603

    Minsk, 220026

  • Investigator Site 3602

    Minsk, 220114

  • Investigator Site 3606

    Vitebsk, 210023

  • Investigator Site 3604

    Vitebsk, 210037

Other trials in Belarus

France5 sites

  • Investigator Site 1713

    Bordeaux, 33076

  • Investigator Site 1703

    Clermont-Ferrand, 63003

  • Investigator Site 1715

    Nantes, 44093

  • Investigator Site 1706

    Nice, 06002

  • Investigator Site 1705

    Strasbourg, 67091

Other trials in France

Georgia5 sites

  • Investigator Site 3905

    Tbilisi, 0112

  • Investigator Site 3904

    Tbilisi, 0160

  • Investigator Site 3903

    Tbilisi, 0179

  • Investigator Site 3906

    Tbilisi, 0179

  • Investigator Site 3902

    Tbilisi, 0194

Other trials in Georgia

Germany5 sites

  • Investigator Site 1113

    Dresden, 01307

  • Investigator Site 1107

    Erfurt, 99089

  • Investigator Site 1109

    Leipzig, 04107

  • Investigator Site 1104

    Mainz, 55131

  • Investigator Site 1102

    Ulm, 89081

Other trials in Germany

Hungary5 sites

  • Investigator Site 2903

    Budapest, 1145

  • Investigator Site 2905

    Budapest, 1204

  • Investigator Site 2910

    Esztergom, 2500

  • Investigator Site 2902

    Győr, 9023

  • Investigator Site 2909

    Kistarcsa, 2143

Other trials in Hungary

Serbia5 sites

  • Investigator Site 2601

    Belgrade, 11000

  • Investigator Site 2606

    Belgrade, 11000

  • Investigator Site 2607

    Belgrade, 11080

  • Investigator Site 2603

    Kragujevac, 34000

  • Investigator Site 2602

    Niš, 18000

Other trials in Serbia

Canada4 sites

  • Investigator Site 8102

    Edmonton, Alberta, T6G 1Z1

  • Investigator Site 8113

    Greenfield Park, Quebec, J4V 2J2

  • Investigator Site 8101

    Ottawa, Ontario, K1H 8L6

  • Investigator Site 8120

    Victoria, British Columbia, V8R 1J8

Other trials in Canada

Croatia4 sites

  • Investigator Site 2506

    Osijek, 31000

  • Investigator Site 2502

    Zagreb, 10000

  • Investigator Site 2508

    Zagreb, 10000

  • Investigator Site 2509

    Zagreb, 10000

Other trials in Croatia

Israel4 sites

  • Investigator Site 4005

    Ashkelon, 7830604

  • Investigator Site 4004

    Haifa, 3109601

  • Investigator Site 4006

    Jerusalem, 9112001

  • Investigator Site 4010

    Zfat, 13100

Other trials in Israel

Italy4 sites

  • Investigator Site 1403

    Cefalù, 90015

  • Investigator Site 1409

    Genova, 16132

  • Investigator Site 1413

    L’Aquila, 67100

  • Investigator Site 1405

    Roma, 00189

Other trials in Italy

Portugal4 sites

  • Investigator Site 1602

    Amadora, 2720 276

  • Investigator Site 1605

    Braga, 4710-243

  • Investigator Site 1603

    Coimbra, 3000-075

  • Investigator Site 1604

    Porto, 4099-001

Other trials in Portugal

Romania4 sites

  • Investigator Site 2807

    Bucharest, 010825

  • Investigator Site 2811

    Bucharest, 022903

  • Investigator Site 2804

    Bucharest, 050098

  • Investigator Site 2802

    Timișoara, 300723

Other trials in Romania

Greece3 sites

  • Investigator Site 1303

    Athens, 11521

  • Investigator Site 1301

    Athens, 11525

  • Investigator Site 1307

    Athens, 15125

Other trials in Greece

Latvia3 sites

  • Investigator Site 3401

    Riga, 1015

  • Investigator Site 3402

    Riga, LV-1002

  • Investigator Site 3403

    Riga, LV-1038

Other trials in Latvia

Lithuania3 sites

  • Investigator Site 3502

    Kaunas, 50161

  • Investigator Site 3503

    Klaipėda, 92288

  • Investigator Site 3504

    Šiauliai, 76231

Other trials in Lithuania

Sweden3 sites

  • Investigator Site 2103

    Gothenburg, 413 45

  • Investigator Site 2110

    Stockholm, 141 86

  • Investigator Site 2101

    Stockholm, 171 76

Other trials in Sweden

United Kingdom3 sites

  • Investigator Site 2015

    Glasgow, G51 4TF

  • Investigator Site 2021

    Lancashire, PR2 9HT

  • Investigator Site 2003

    Salford, M6 8HD

Other trials in United Kingdom

Finland2 sites

  • Investigator Site 2212

    Tampere, 33100

  • Investigator Site 2202

    Turku, 20520

Other trials in Finland

Mexico2 sites

  • Investigator Site 7410

    Chihuahua City, 31203

  • Investigator Site 7409

    Monterrey, 64710

Other trials in Mexico

Bosnia and Herzegovina1 site

  • Investigator Site 9104

    Sarajevo, 71000

Other trials in Bosnia and Herzegovina

Turkey (Türkiye)1 site

  • Investigator Site 9004

    Trabzon, 61080

Other trials in Turkey (Türkiye)

About this study

Official title: Multicenter, Randomized, Double-blind, Parallel-group, Active-controlled, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Teriflunomide in Subjects With Relapsing Multiple Sclerosis

International clinical trial to compare ponesimod and teriflunomide in relapsing multiple sclerosis

Being tested
ponesimod, teriflunomide
Keywords
relapsing multiple sclerosis
Medical subject headings
Multiple Sclerosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ponesimodDrug

    Also called ACT-128800

    film-coated tablet with 20 mg ponesimod, administered orally once daily in the morning

  • teriflunomideDrug

    film-coated tablet with 14 mg teriflunomide, administered orally once daily in the morning

Study groups in NCT02425644
Study groupRoleWhat they receive
PonesimodExperimentalSubjects to receive 20 mg ponesimod
Receives: Drug: ponesimod
TeriflunomideActive comparatorSubjects to receive 14 mg teriflunomide
Receives: Drug: teriflunomide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Annualized Confirmed Relapse Rate

    Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual,Brain Stem,Pyramidal,Cerebellar,Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS).

    Measured: From randomization to end of study (Week 108)

Secondary outcomes (4)

  1. Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108

    The FSIQ-RMS is a 20-item Patient Reported Outcomes (PRO) measure to evaluate fatigue-related symptoms and the impacts of those symptoms on the lives of people. The FSIQ-RMS symptom domain (FSIQ-RMS-S) consists of seven items assessing fatigue-related symptoms daily with a recall period of 24 hours measured on an 11-point numeric rating scale; the (normalized) symptom domain score ranges from 0 to 100 with a higher score indicating greater fatigue. This domain was completed on 7 consecutive days. A negative change from baseline indicates an improvement in fatigue symptoms.

    Measured: Baseline to Week 108

  2. Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108

    CUALs was calculated as sum of new Gadolinium-enhanced (Gd+) T1 lesions plus new or enlarging T2 lesions (without double-counting of lesions) from baseline based on the Magnetic resonance imaging (MRI) scans up to Week 108. Average number of lesions per year were reported.

    Measured: Baseline to Week 108

  3. 12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

    A 12-week CDA was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS).

    Measured: Baseline to Week 60 and 108 Weeks

  4. 24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS

    A 24-week CDA was defined as an increase of at least 1.5 in EDSS for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score >= 5.5, which was confirmed after 24 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. The EDSS is an ordinal scale ranging from 0 (normal neurological exam) to 10 (death to MS).

    Measured: Baseline to 60 Weeks and 108 Weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2015 (estimated)
  2. Study start4 Jun 2015
  3. Primary completion16 May 2019
  4. Study completion16 May 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
1,133 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02425644
Sponsor's protocol ID
AC-058B301
Other IDs
2012-000540-10
Acronym
OPTIMUM
Status last verified
Mar 2025
First submitted
21 Apr 2015
Last updated
30 Mar 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Jones RR, Turkoz I, Ait-Tihyaty M, DiBernardo A, Houtchens MK, Havrdova EK. Efficacy and Safety of Ponesimod Compared with Teriflunomide in Female Patients with Relapsing Multiple Sclerosis: Findings from the Pivotal OPTIMUM Study. J Womens Health (Larchmt). 2024 Apr;33(4):480-490. doi: 10.1089/jwh.2023.0037. Epub 2024 Feb 1.

    PubMed 38301149

  • Jiang T, Ziemssen T, Wray S, Shen C, Soderbarg K, Lewin JB, Bozin I, Freedman MS. Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. CNS Drugs. 2023 May;37(5):441-452. doi: 10.1007/s40263-023-01002-x. Epub 2023 May 8.

    PubMed 37155132

  • Fox RJ, Tervonen T, Phillips-Beyer A, Sidorenko T, Boyanova N, Brooks A, Hennessy B, Jamieson C, Levitan B. The relevance of fatigue to relapse rate in multiple sclerosis: Applying patient preference data to the OPTIMUM trial. Mult Scler. 2023 Mar;29(3):427-435. doi: 10.1177/13524585221140270. Epub 2022 Dec 22.

    PubMed 36550636

  • Valenzuela B, Olsson Gisleskog P, Poggesi I, Sidorenko T, Burcklen M, Kracker H, Perez-Ruixo JJ. An exposure-response analysis of ponesimod clinical efficacy in a randomized phase III study in patients with relapsing multiple sclerosis. CPT Pharmacometrics Syst Pharmacol. 2022 Oct;11(10):1294-1304. doi: 10.1002/psp4.12778. Epub 2022 Sep 1.

    PubMed 36047474

  • Kappos L, Fox RJ, Burcklen M, Freedman MS, Havrdova EK, Hennessy B, Hohlfeld R, Lublin F, Montalban X, Pozzilli C, Scherz T, D'Ambrosio D, Linscheid P, Vaclavkova A, Pirozek-Lawniczek M, Kracker H, Sprenger T. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. 2021 May 1;78(5):558-567. doi: 10.1001/jamaneurol.2021.0405.

    PubMed 33779698

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing ponesimod and teriflunomide in people with Multiple Sclerosis, run by Actelion at 162 sites in 28 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 30 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 162 sites in Russia, Ukraine, Poland, United States, Czechia and 23 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jun 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Annualized Confirmed Relapse Rate (time frame: From randomization to end of study (Week 108)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02425644, which also lists 5 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2025.

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