Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis

NCT ID: NCT02425644

Last Updated: 2025-03-30

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1133 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-04
• Study Completion Date: 2019-05-16

Brief Summary

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

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Ponesimod

Subjects to receive 20 mg ponesimod

Group Type: EXPERIMENTAL

ponesimod

Intervention Type: DRUG

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

Teriflunomide

Subjects to receive 14 mg teriflunomide

Group Type: ACTIVE_COMPARATOR

teriflunomide

Intervention Type: DRUG

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

Interventions

ponesimod

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

Intervention Type: DRUG

teriflunomide

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

Intervention Type: DRUG

Other Intervention Names

ACT-128800

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tatiana Scherz, MD, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

Investigator Site 8045

Carlsbad, California, United States

Investigator Site 8311

Pomona, California, United States

Investigator Site 8036

Denver, Colorado, United States

Investigator Site 8065

Ormond Beach, Florida, United States

Investigator Site 8018

Tampa, Florida, United States

Investigator Site 8013

Indianapolis, Indiana, United States

Investigator Site 8040

Raleigh, North Carolina, United States

Investigator Site 8006

Columbus, Ohio, United States

Investigator Site 8015

Franklin, Tennessee, United States

Investigator Site 8042

Orem, Utah, United States

Investigator Site 3605

Grodno, , Belarus

Investigator Site 3603

Minsk, , Belarus

Investigator Site 3602

Minsk, , Belarus

Investigator Site 3606

Vitebsk, , Belarus

Investigator Site 3604

Vitebsk, , Belarus

Investigator Site 9104

Sarajevo, , Bosnia and Herzegovina

Investigator Site 2709

Plovdiv, , Bulgaria

Investigator Site 2711

Sofia, , Bulgaria

Investigator Site 2702

Sofia, , Bulgaria

Investigator Site 2707

Sofia, , Bulgaria

Investigator Site 2701

Sofia, , Bulgaria

Investigator Site 2708

Sofia, , Bulgaria

Investigator Site 2703

Sofia, , Bulgaria

Investigator Site 8102

Edmonton, Alberta, Canada

Investigator Site 8120

Victoria, British Columbia, Canada

Investigator Site 8101

Ottawa, Ontario, Canada

Investigator Site 8113

Greenfield Park, Quebec, Canada

Investigator Site 2506

Osijek, , Croatia

Investigator Site 2502

Zagreb, , Croatia

Investigator Site 2508

Zagreb, , Croatia

Investigator Site 2509

Zagreb, , Croatia

Investigator Site 3009

Brno, , Czechia

Investigator Site 3003

Brno, , Czechia

Investigator Site 3010

Hradec Králové, , Czechia

Investigator Site 3006

Jihlava, , Czechia

Investigator Site 3002

Ostrava-Poruba, , Czechia

Investigator Site 3007

Pardubice, , Czechia

Investigator Site 3001

Prague, , Czechia

Investigator Site 3008

Prague, , Czechia

Investigator Site 3004

Teplice, , Czechia

Investigator Site 2212

Tampere, , Finland

Investigator Site 2202

Turku, , Finland

Investigator Site 1713

Bordeaux, , France

Investigator Site 1703

Clermont-Ferrand, , France

Investigator Site 1715

Nantes, , France

Investigator Site 1706

Nice, , France

Investigator Site 1705

Strasbourg, , France

Investigator Site 3905

Tbilisi, , Georgia

Investigator Site 3904

Tbilisi, , Georgia

Investigator Site 3903

Tbilisi, , Georgia

Investigator Site 3906

Tbilisi, , Georgia

Investigator Site 3902

Tbilisi, , Georgia

Investigator Site 1113

Dresden, , Germany

Investigator Site 1107

Erfurt, , Germany

Investigator Site 1109

Leipzig, , Germany

Investigator Site 1104

Mainz, , Germany

Investigator Site 1102

Ulm, , Germany

Investigator Site 1303

Athens, , Greece

Investigator Site 1301

Athens, , Greece

Investigator Site 1307

Athens, , Greece

Investigator Site 2903

Budapest, , Hungary

Investigator Site 2905

Budapest, , Hungary

Investigator Site 2910

Esztergom, , Hungary

Investigator Site 2902

Győr, , Hungary

Investigator Site 2909

Kistarcsa, , Hungary

Investigator Site 4005

Ashkelon, , Israel

Investigator Site 4004

Haifa, , Israel

Investigator Site 4006

Jerusalem, , Israel

Investigator Site 4010

Zfat, , Israel

Investigator Site 1403

Cefalù, , Italy

Investigator Site 1409

Genova, , Italy

Investigator Site 1413

L’Aquila, , Italy

Investigator Site 1405

Roma, , Italy

Investigator Site 3401

Riga, , Latvia

Investigator Site 3402

Riga, , Latvia

Investigator Site 3403

Riga, , Latvia

Investigator Site 3502

Kaunas, , Lithuania

Investigator Site 3503

Klaipėda, , Lithuania

Investigator Site 3504

Šiauliai, , Lithuania

Investigator Site 7410

Chihuahua City, , Mexico

Investigator Site 7409

Monterrey, , Mexico

Investigator Site 3219

Bialystok, , Poland

Investigator Site 3215

Bydgoszcz, , Poland

Investigator Site 3208

Gdansk, , Poland

Investigator Site 3217

Katowice, , Poland

Investigator Site 3203

Katowice, , Poland

Investigator Site 3205

Konstancin-Jeziorna, , Poland

Investigator Site 3216

Ksawerów, , Poland

Investigator Site 3220

Lublin, , Poland

Investigator Site 3202

Poznan, , Poland

Investigator Site 3214

Poznan, , Poland

Investigator Site 3207

Poznan, , Poland

Investigator Site 3213

Wroclaw, , Poland

Investigator Site 1602

Amadora, , Portugal

Investigator Site 1605

Braga, , Portugal

Investigator Site 1603

Coimbra, , Portugal

Investigator Site 1604

Porto, , Portugal

Investigator Site 2807

Bucharest, , Romania

Investigator Site 2811

Bucharest, , Romania

Investigator Site 2804

Bucharest, , Romania

Investigator Site 2802

Timișoara, , Romania

Investigator Site 3821

Barnaul, Altayskiy Kray, Russia

Investigator Site 3818

Belgorod, , Russia

Investigator Site 3837

Bryansk, , Russia

Investigator Site 3811

Kazan', , Russia

Investigator Site 3822

Kemerovo, , Russia

Investigator Site 3814

Krasnoyarsk, , Russia

Investigator Site 3823

Kursk, , Russia

Investigator Site 3831

Moscow, , Russia

Investigator Site 3803

Moscow, , Russia

Investigator Site 3840

Moscow, , Russia

Investigator Site 3810

Moscow, , Russia

Investigator Site 3834

Nizhny Novgorod, , Russia

Investigator Site 3802

Nizhny Novgorod, , Russia

Investigator Site 3829

Novosibirsk, , Russia

Investigator Site 3839

Perm, , Russia

Investigator Site 3812

Pyatigorsk, , Russia

Investigator Site 3808

Saint Petersburg, , Russia

Investigator Site 3833

Saint Petersburg, , Russia

Investigator Site 3813

Saint Petersburg, , Russia

Investigator Site 3807

Saint Petersburg, , Russia

Investigator Site 3815

Saint Petersburg, , Russia

Investigator Site 3805

Samara, , Russia

Investigator Site 3825

Smolensk, , Russia

Investigator Site 3801

Tomsk, , Russia

Investigator Site 3819

Tver', , Russia

Investigator Site 3835

Veliky Novgorod, , Russia

Investigator Site 3842

Yaroslavl, , Russia

Investigator Site 3836

Yekaterinburg, , Russia

Investigator Site 2601

Belgrade, , Serbia

Investigator Site 2606

Belgrade, , Serbia

Investigator Site 2607

Belgrade, , Serbia

Investigator Site 2603

Kragujevac, , Serbia

Investigator Site 2602

Niš, , Serbia

Investigator Site 1509

Barcelona, , Spain

Investigator Site 1505

Barcelona, , Spain

Investigator Site 1504

Barcelona, , Spain

Investigator Site 1502

Madrid, , Spain

Investigator Site 1501

Málaga, , Spain

Investigator Site 1506

Seville, , Spain

Investigator Site 2103

Gothenburg, , Sweden

Investigator Site 2110

Stockholm, , Sweden

Investigator Site 2101

Stockholm, , Sweden

Investigator Site 9004

Trabzon, , Turkey (Türkiye)

Investigator Site 3714

Chernihiv, , Ukraine

Investigator Site 3701

Chernihiv, , Ukraine

Investigator Site 3713

Ivano-Frankivsk, , Ukraine

Investigator Site 3711

Ivano-Frankivsk, , Ukraine

Investigator Site 3723

Kharkiv, , Ukraine

Investigator Site 3724

Kharkiv, , Ukraine

Investigator Site 3716

Kyiv, , Ukraine

Investigator Site 3715

Lviv, , Ukraine

Investigator Site 3721

Lviv, , Ukraine

Investigator Site 3703

Odesa, , Ukraine

Investigator Site 3717

Poltava, , Ukraine

Investigator Site 3730

Ternopil, , Ukraine

Investigator Site 3718

Vinnytsia, , Ukraine

Investigator Site 3722

Zaporizhia, , Ukraine

Investigator Site 3725

Zhytomyr, , Ukraine

Investigator Site 2015

Glasgow, , United Kingdom

Investigator Site 2021

Lancashire, , United Kingdom

Investigator Site 2003

Salford, , United Kingdom

Countries

United States; Belarus; Bosnia and Herzegovina; Bulgaria; Canada; Croatia; Czechia; Finland; France; Georgia; Germany; Greece; Hungary; Israel; Italy; Latvia; Lithuania; Mexico; Poland; Portugal; Romania; Russia; Serbia; Spain; Sweden; Turkey (Türkiye); Ukraine; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 38301149 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 37155132 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36550636 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 36047474 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 33779698 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://filehosting-v2.pharmacm.com/api/Attachment/Download?tenantId=80217051&parentIdentifier=AC-058B301&attachmentIdentifier=24f4f084-9a98-4430-a172-80d455f49865&fileName=AC-058B301_Additional_result_data_CH.pdf&versionIdentifier=

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

Other Identifiers

2012-000540-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-058B301

Identifier Type: -

Identifier Source: org_study_id