Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis

NCT02425644 | Completed Phase 3 Results DMC FDA Drug

• 2 other identifiers: AC-058B3012012-000540-10
• Study Type: interventional
• Target: 1,133
• Locations: 27 countries
• Sites: 157

Brief Summary

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

Conditions

Multiple Sclerosis

Keywords

relapsing multiple sclerosis

Outcome Measures

Primary Outcomes (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).

  From randomization to end of study (Week 108)

Secondary Outcomes (4)

• 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

  Baseline to Week 108

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

  Baseline to Week 108

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

  Baseline to Week 60 and 108 Weeks

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

  Baseline to 60 Weeks and 108 Weeks

Study Arms (2)

Ponesimod

EXPERIMENTAL

Subjects to receive 20 mg ponesimod

Drug: ponesimod

Teriflunomide

ACTIVE COMPARATOR

Subjects to receive 14 mg teriflunomide

Drug: teriflunomide

Interventions

ponesimod DRUG

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

Also known as: ACT-128800

Ponesimod

teriflunomide DRUG

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

Teriflunomide

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Actelion: lead

Study Sites (162)

Investigator Site 8045

Carlsbad, California, 92011, United States

Location

Investigator Site 8311

Pomona, California, 91767, United States

Location

Investigator Site 8036

Denver, Colorado, 80209, United States

Location

Investigator Site 8065

Ormond Beach, Florida, 32174, United States

Location

Investigator Site 8018

Tampa, Florida, 33612, United States

Location

Investigator Site 8013

Indianapolis, Indiana, 46256, United States

Location

Investigator Site 8040

Raleigh, North Carolina, 27607, United States

Location

Investigator Site 8006

Columbus, Ohio, 43214, United States

Location

Investigator Site 8015

Franklin, Tennessee, 37064, United States

Location

Investigator Site 8042

Orem, Utah, 84058, United States

Location

Investigator Site 3605

Grodno, 230017, Belarus

Location

Investigator Site 3603

Minsk, 220026, Belarus

Location

Investigator Site 3602

Minsk, 220114, Belarus

Location

Investigator Site 3606

Vitebsk, 210023, Belarus

Location

Investigator Site 3604

Vitebsk, 210037, Belarus

Location

Investigator Site 9104

Sarajevo, 71000, Bosnia and Herzegovina

Location

Investigator Site 2709

Plovdiv, 4002, Bulgaria

Location

Investigator Site 2711

Sofia, 1113, Bulgaria

Location

Investigator Site 2702

Sofia, 1309, Bulgaria

Location

Investigator Site 2707

Sofia, 1407, Bulgaria

Location

Investigator Site 2701

Sofia, 1431, Bulgaria

Location

Investigator Site 2708

Sofia, 1431, Bulgaria

Location

Investigator Site 2703

Sofia, 1606, Bulgaria

Location

Investigator Site 8102

Edmonton, Alberta, T6G 1Z1, Canada

Location

Investigator Site 8120

Victoria, British Columbia, V8R 1J8, Canada

Location

Investigator Site 8101

Ottawa, Ontario, K1H 8L6, Canada

Location

Investigator Site 8113

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Investigator Site 2506

Osijek, 31000, Croatia

Location

Investigator Site 2502

Zagreb, 10000, Croatia

Location

Investigator Site 2508

Zagreb, 10000, Croatia

Location

Investigator Site 2509

Zagreb, 10000, Croatia

Location

Investigator Site 3009

Brno, 625 00, Czechia

Location

Investigator Site 3003

Brno, 656 91, Czechia

Location

Investigator Site 3010

Hradec Králové, 500 05, Czechia

Location

Investigator Site 3006

Jihlava, 586 33, Czechia

Location

Investigator Site 3002

Ostrava-Poruba, 708 52, Czechia

Location

Investigator Site 3007

Pardubice, 532 03, Czechia

Location

Investigator Site 3001

Prague, 128 08, Czechia

Location

Investigator Site 3008

Prague, 150 06, Czechia

Location

Investigator Site 3004

Teplice, 415 29, Czechia

Location

Investigator Site 2212

Tampere, 33100, Finland

Location

Investigator Site 2202

Turku, 20520, Finland

Location

Investigator Site 1713

Bordeaux, 33076, France

Location

Investigator Site 1703

Clermont-Ferrand, 63003, France

Location

Investigator Site 1715

Nantes, 44093, France

Location

Investigator Site 1706

Nice, 06002, France

Location

Investigator Site 1705

Strasbourg, 67091, France

Location

Investigator Site 3905

Tbilisi, 0112, Georgia

Location

Investigator Site 3904

Tbilisi, 0160, Georgia

Location

Investigator Site 3903

Tbilisi, 0179, Georgia

Location

Investigator Site 3906

Tbilisi, 0179, Georgia

Location

Investigator Site 3902

Tbilisi, 0194, Georgia

Location

Investigator Site 1113

Dresden, 01307, Germany

Location

Investigator Site 1107

Erfurt, 99089, Germany

Location

Investigator Site 1109

Leipzig, 04107, Germany

Location

Investigator Site 1104

Mainz, 55131, Germany

Location

Investigator Site 1102

Ulm, 89081, Germany

Location

Investigator Site 1303

Athens, 11521, Greece

Location

Investigator Site 1301

Athens, 11525, Greece

Location

Investigator Site 1307

Athens, 15125, Greece

Location

Investigator Site 2903

Budapest, 1145, Hungary

Location

Investigator Site 2905

Budapest, 1204, Hungary

Location

Investigator Site 2910

Esztergom, 2500, Hungary

Location

Investigator Site 2902

Győr, 9023, Hungary

Location

Investigator Site 2909

Kistarcsa, 2143, Hungary

Location

Investigator Site 4005

Ashkelon, 7830604, Israel

Location

Investigator Site 4004

Haifa, 3109601, Israel

Location

Investigator Site 4006

Jerusalem, 9112001, Israel

Location

Investigator Site 4010

Zfat, 13100, Israel

Location

Investigator Site 1403

Cefalù, 90015, Italy

Location

Investigator Site 1409

Genova, 16132, Italy

Location

Investigator Site 1413

L’Aquila, 67100, Italy

Location

Investigator Site 1405

Roma, 00189, Italy

Location

Investigator Site 3401

Riga, 1015, Latvia

Location

Investigator Site 3402

Riga, LV-1002, Latvia

Location

Investigator Site 3403

Riga, LV-1038, Latvia

Location

Investigator Site 3502

Kaunas, 50161, Lithuania

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Investigator Site 3503

Klaipėda, 92288, Lithuania

Location

Investigator Site 3504

Šiauliai, 76231, Lithuania

Location

Investigator Site 7410

Chihuahua City, 31203, Mexico

Location

Investigator Site 7409

Monterrey, 64710, Mexico

Location

Investigator Site 3219

Bialystok, 15-270, Poland

Location

Investigator Site 3215

Bydgoszcz, 85-795, Poland

Location

Investigator Site 3208

Gdansk, 80-803, Poland

Location

Investigator Site 3217

Katowice, 40-595, Poland

Location

Investigator Site 3203

Katowice, 40-752, Poland

Location

Investigator Site 3205

Konstancin-Jeziorna, 05-510, Poland

Location

Investigator Site 3216

Ksawerów, 95-054, Poland

Location

Investigator Site 3220

Lublin, 20-015, Poland

Location

Investigator Site 3202

Poznan, 60-355, Poland

Location

Investigator Site 3214

Poznan, 60-848, Poland

Location

Investigator Site 3207

Poznan, 61-853, Poland

Location

Investigator Site 3213

Wroclaw, 51-685, Poland

Location

Investigator Site 1602

Amadora, 2720 276, Portugal

Location

Investigator Site 1605

Braga, 4710-243, Portugal

Location

Investigator Site 1603

Coimbra, 3000-075, Portugal

Location

Investigator Site 1604

Porto, 4099-001, Portugal

Location

Investigator Site 2807

Bucharest, 010825, Romania

Location

Investigator Site 2811

Bucharest, 022903, Romania

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Investigator Site 2804

Bucharest, 050098, Romania

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Investigator Site 2802

Timișoara, 300723, Romania

Location

Investigator Site 3821

Barnaul, Altayskiy Kray, 656024, Russia

Location

Investigator Site 3818

Belgorod, 308007, Russia

Location

Investigator Site 3837

Bryansk, 241033, Russia

Location

Investigator Site 3811

Kazan', 420029, Russia

Location

Investigator Site 3822

Kemerovo, 650066, Russia

Location

Investigator Site 3814

Krasnoyarsk, 660037, Russia

Location

Investigator Site 3823

Kursk, 305007, Russia

Location

Investigator Site 3831

Moscow, 119049, Russia

Location

Investigator Site 3803

Moscow, 127015, Russia

Location

Investigator Site 3840

Moscow, 127015, Russia

Location

Investigator Site 3810

Moscow, 129128, Russia

Location

Investigator Site 3834

Nizhny Novgorod, 603076, Russia

Location

Investigator Site 3802

Nizhny Novgorod, 603155, Russia

Location

Investigator Site 3829

Novosibirsk, 630007, Russia

Location

Investigator Site 3839

Perm, 614990, Russia

Location

Investigator Site 3812

Pyatigorsk, 357538, Russia

Location

Investigator Site 3808

Saint Petersburg, 194354, Russia

Location

Investigator Site 3833

Saint Petersburg, 197022, Russia

Location

Investigator Site 3813

Saint Petersburg, 197110, Russia

Location

Investigator Site 3807

Saint Petersburg, 197376, Russia

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Investigator Site 3815

Saint Petersburg, 197706, Russia

Location

Investigator Site 3805

Samara, 443095, Russia

Location

Investigator Site 3825

Smolensk, 214019, Russia

Location

Investigator Site 3801

Tomsk, 634050, Russia

Location

Investigator Site 3819

Tver', 170026, Russia

Location

Investigator Site 3835

Veliky Novgorod, 173008, Russia

Location

Investigator Site 3842

Yaroslavl, 150030, Russia

Location

Investigator Site 3836

Yekaterinburg, 620102, Russia

Location

Investigator Site 2601

Belgrade, 11000, Serbia

Location

Investigator Site 2606

Belgrade, 11000, Serbia

Location

Investigator Site 2607

Belgrade, 11080, Serbia

Location

Investigator Site 2603

Kragujevac, 34000, Serbia

Location

Investigator Site 2602

Niš, 18000, Serbia

Location

Investigator Site 1509

Barcelona, 08003, Spain

Location

Investigator Site 1505

Barcelona, 08035, Spain

Location

Investigator Site 1504

Barcelona, 08036, Spain

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Investigator Site 1502

Madrid, 28006, Spain

Location

Investigator Site 1501

Málaga, 29010, Spain

Location

Investigator Site 1506

Seville, 41009, Spain

Location

Investigator Site 2103

Gothenburg, 413 45, Sweden

Location

Investigator Site 2110

Stockholm, 141 86, Sweden

Location

Investigator Site 2101

Stockholm, 171 76, Sweden

Location

Investigator Site 9004

Trabzon, 61080, Turkey (Türkiye)

Location

Investigator Site 3714

Chernihiv, 14001, Ukraine

Location

Investigator Site 3701

Chernihiv, 14029, Ukraine

Location

Investigator Site 3713

Ivano-Frankivsk, 76008, Ukraine

Location

Investigator Site 3711

Ivano-Frankivsk, 76018, Ukraine

Location

Investigator Site 3723

Kharkiv, 61103, Ukraine

Location

Investigator Site 3724

Kharkiv, 61176, Ukraine

Location

Investigator Site 3716

Kyiv, 03115, Ukraine

Location

Investigator Site 3715

Lviv, 79000, Ukraine

Location

Investigator Site 3721

Lviv, 79010, Ukraine

Location

Investigator Site 3703

Odesa, 65009, Ukraine

Location

Investigator Site 3717

Poltava, 36011, Ukraine

Location

Investigator Site 3730

Ternopil, 46027, Ukraine

Location

Investigator Site 3718

Vinnytsia, 21005, Ukraine

Location

Investigator Site 3722

Zaporizhia, 69000, Ukraine

Location

Investigator Site 3725

Zhytomyr, 10008, Ukraine

Location

Investigator Site 2015

Glasgow, G51 4TF, United Kingdom

Location

Investigator Site 2021

Lancashire, PR2 9HT, United Kingdom

Location

Investigator Site 2003

Salford, M6 8HD, United Kingdom

Location

Related Publications (5)

• 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.

  PMID: 38301149 DERIVED

• 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.

  PMID: 37155132 DERIVED

• 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.

  PMID: 36550636 DERIVED

• 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.

  PMID: 36047474 DERIVED

• 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.

  PMID: 33779698 DERIVED

Related Links

• 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

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ponesimod; teriflunomide

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Limitations and Caveats

Low probability of this study to provide robust evaluation of ponesimod effect on disability accumulation compared to active comparator; study was not powered for this secondary endpoint. Impact of accelerated elimination procedure during safety follow-up: Accelerated elimination procedure for teriflunomide with cholestyramine/activated charcoal was frequently associated with benign, transient elevation in liver enzymes. Confounding effect of this procedure on assessing liver test was included.

Results Point of Contact

• Title: Senior Director Clinical Leader
• Organization: Actelion Pharmaceuticals Ltd (a Janssen Pharmaceutical Company of Johnson & Johnson)

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Tatiana Scherz, MD, PhD

  Actelion

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 21, 2015
• First Posted: April 24, 2015
• Study Start: June 4, 2015
• Primary Completion: May 16, 2019
• Study Completion: May 16, 2019
• Last Updated: March 30, 2025
• Results First Posted: June 11, 2021

Record last verified: 2025-03

Locations

ME (2); FR (5); CZ (9); BU (7); CA (4); DE (5); LA (3); LI (3); PT (4); RU (28); SE (3); GB (3); BE (5); US (10); GR (3); BO (1); FI (2); GE (5); HU (5); RO (4); IT (4); IL (4); PL (12); TU (1); ES (6); CR (4); UA (15)