Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis

NCT ID: NCT03232073

Last Updated: 2025-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 877 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-07-05
• Study Completion Date: 2024-01-16

Brief Summary

The study AC-058B301 (OPTIMUM; NCT02425644) has been designed to investigate the efficacy, safety and tolerability of ponesimod in subjects with relapsing multiple sclerosis (RMS). The AC-058B303 study is the long-term extension for the core study AC-058B301. The purpose of this long term extension of the core study AC-058B301 is to characterize the long-term safety, tolerability, and control of disease of ponesimod 20 mg in subjects with RMS.

Detailed Description

The AC-058B303 study (extension study) is the long-term extension for the AC-058B301 study (core study). The core study has been designed to investigate the efficacy, safety and tolerability of ponesimod in subjects with RMS. The subjects are treated with either ponesimod or the active comparator, teriflunomide in the core study. The purpose of this long term extension of the core study is to characterize the long-term safety and control of disease of ponesimod in subjects with RMS. In particular, the study will allow to observe potential adverse events which may only occur after long term treatment with ponesimod. The study will also investigate the effect of re-initiation of ponesimod after a brief interruption in a relatively large population (all subjects treated with ponesimod in the core study and eligible for the extension study) on disease activity in terms of relapses and MS-related MRI lesions. There is currently limited guidance on when a new MS treatment should be started after discontinuation of teriflunomide and the study will contribute with data on safety and efficacy of switching from teriflunomide to ponesimod after an interruption as mandated by the protocol. The study will also allow confirmation of sustained efficacy of ponesimod in terms of relapses, MRI lesions and reduction of disability accumulation during long-term treatment. In addition, combined data from the core study together with the results of the current extension study will allow comparison of MS activity in subjects who were switched from teriflunomide to ponesimod versus those who were treated with ponesimod in both studies.

Conditions

Multiple Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Ponesimod

20 mg administered orally once daily

Group Type: EXPERIMENTAL

Ponesimod

Intervention Type: DRUG

Ponesimod; Film-coated tablet; Oral use. From Day 1 to Day 14, ponesimod is gradually up-titrated until a maintenance dose of 20 mg is reached from Day 15

Interventions

Ponesimod

Ponesimod; Film-coated tablet; Oral use. From Day 1 to Day 14, ponesimod is gradually up-titrated until a maintenance dose of 20 mg is reached from Day 15

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Signed informed consent

2. Subjects with MS having completed the double-blind treatment in the core study as scheduled

3. Compliance with teriflunomide elimination procedure

4. Women of childbearing potential (WOCBP) must have a negative pre-treatment urine pregnancy test, must agree to undertake 4-weekly urine pregnancy tests, and must have been using reliable methods of contraception. Fertile male subjects participating in the study must agree to use a condom.

Exclusion Criteria

1. Any of the following cardiovascular conditions on Day 1 pre-dose:

1. Resting heart rate (HR) < 50 bpm;

2. Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval > 470 ms (females), > 450 ms (males);

2. Any of the following alerts from central laboratory at Visit 14 of the core study (EOT) which was confirmed as an alert at repeated testing or not repeated prior to FU1 of the core study:

1. Lymphocyte count: < 0.2 x 109/L;

2. Neutrophil count <1.0 × 109/L;

3. Platelet count < 50 × 109/L;

4. Creatinine clearance < 30 mL/min

3. At Visit 14 of the core study (EOT) >30% decrease from core study baseline FEV1 and/or FVC;

4. Clinically significant, persistent respiratory AEs (e.g., dyspnea) not resolved prior to first dosing in the extension study.

5. Macular edema at any time between Visit 1 (Screening) in the core study and Day 1 of the extension study.

6. Presence of the following at core study Visit 14 (EOT, Week 108), FU1, or abbreviated visit FU2, or on Day 1 of the extension study pre-dose:

1. Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study drug;

2. Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.

7. Need for and intention to administer forbidden study treatment-concomitant therapy

8. Women who are pregnant or lactating.

9. Male subjects wishing to parent a child;

10. Treatment with any MS Disease Modifying Therapies;

11. Any other clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the subject at risk by participating in the study;

12. Subjects unlikely to comply with the extension study protocol based on investigator best judgment

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Actelion

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tatiana Sidorenko, MD, PhD

Role: STUDY_DIRECTOR

Actelion

Locations

The Research Center of Southern California, LLC

Carlsbad, California, United States

The Neurology Group

Pomona, California, United States

Mountain View Clinical Research

Denver, Colorado, United States

Neurology Associates of Ormond Beach

Ormond Beach, Florida, United States

University of South Florida

Tampa, Florida, United States

Josephson Wallack Munshower Neurology, PC

Indianapolis, Indiana, United States

Raleigh Neurology Associates

Raleigh, North Carolina, United States

Ohio Health

Columbus, Ohio, United States

Advanced Neurosciences Institute

Franklin, Tennessee, United States

Grodno University Hospital

Grodno, , Belarus

Minsk City Clinical Hospital 5

Minsk, , Belarus

Republican Scientific Clinical Centre

Minsk, , Belarus

Vitebsk Regional Diagnostic Center

Vitebsk, , Belarus

Vitebsk Regional Clinical Hospital

Vitebsk, , Belarus

University Clinicl Center Sarajevo

Sarajevo, , Bosnia and Herzegovina

UMHAT Sveti Georgi

Plovdiv, , Bulgaria

Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum

Sofia, , Bulgaria

Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead

Sofia, , Bulgaria

Acibadem City Clinic Tokuda Hospital

Sofia, , Bulgaria

St Ivan Rilski University Multiprofile Hospital For Active Treatment

Sofia, , Bulgaria

University Multiprofile Hospital for Active Treatment Alexandrovska EAD

Sofia, , Bulgaria

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia

Sofia, , Bulgaria

University of Alberta

Edmonton, Alberta, Canada

Royal Jubilee Hospital

Victoria, British Columbia, Canada

Ottawa Hospital

Ottawa, Ontario, Canada

Recherche Sepmus Inc.

Greenfield Park, Quebec, Canada

Ch Osijek

Osijek, , Croatia

University Hospital Center Zagreb

Zagreb, , Croatia

Fakultní nemocnici Brno

Brno, , Czechia

Fakultni nemocnice Hradec Kralove

Hradec Králové, , Czechia

Nemocnice Jihlava

Jihlava, , Czechia

Fakultni Nemocnice Ostrava

Ostrava-Poruba, , Czechia

Pardubicka krajska nemocnice a s

Pardubice, , Czechia

Vseobecna Fakultní Nemocnice

Prague, , Czechia

FN Motol

Prague, , Czechia

Krajska zdravotni, a.s. - Nemocnice Teplice, o.z.

Teplice, , Czechia

Suomen Terveystalo Tampere

Tampere, , Finland

Mehilainen NEO

Turku, , Finland

Hopital Pellegrin CHU Bordeaux

Bordeaux, , France

CHU Clermont-Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, , France

Hopital Nord Laennec CHU NANTES

Nantes, , France

Hopital PASTEUR

Nice, , France

Nouvel Hopital Civil

Strasbourg, , France

LTD 'Aversi Clinic'

T'bilisi, , Georgia

P. Sarajishvili Institute of Neurology

Tbilisi, , Georgia

Pineo Medical Ecosystem Ltd

Tbilisi, , Georgia

S.Khechinashvili University Hospital

Tbilisi, , Georgia

Curatio, Jsc

Tbilisi, , Georgia

Universitätsklinikum Carl-Gustav-Carus Dresden

Dresden, , Germany

Helios Klinikum Erfurt

Erfurt, , Germany

Panakeia - Arzneimittelforschung GmbH

Leipzig, , Germany

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, , Germany

401 Military Hospital

Athens, , Greece

Naval Hospital of Athens

Athens, , Greece

Medical Center of Athens

Marousi, , Greece

Uzsoki Utcai Korhaz

Budapest, , Hungary

Jahn Ferenc Del-pesti Korhaz es Rendelointezet

Budapest, , Hungary

Valeomed EGÉSZSÉGÜGYI KÖZPONT

Esztergom, , Hungary

Petz Aladar Megyei Oktato Korhaz

Győr, , Hungary

Kistarcsai Flor Ferenc Korhaz

Kistarcsa, , Hungary

Barzilai Medical Center

Ashkelon, , Israel

Rambam Medical Center

Haifa, , Israel

Hadassah Medical Center

Jerusalem, , Israel

Ziv Medical Center

Safed, , Israel

Ospedale San Salvatore

L’Aquila, , Italy

Azienda Ospedaliera Sant Andrea

Roma, , Italy

Pauls Stradins Clinical University Hospital

Riga, , Latvia

Latvias Juras medicinas centrs Ltd

Riga, , Latvia

Rīgas Austrumu klīniskā universitātes slimnīca

Riga, , Latvia

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, , Lithuania

VsI Respublikine Siauliu ligonine, V.

Šiauliai, , Lithuania

Unidad de Investigacion En Salud

Chihuahua City, , Mexico

CRI Centro Regiomontano de Investigacion SC

Nuevo León, , Mexico

Neurocentrum Bydgoszcz Sp Z O O

Bydgoszcz, , Poland

Copernicus Podmiot Leczniczy Sp. z o.o

Gdansk, , Poland

Neuro Centrum Centrum Terapii SM

Katowice, , Poland

NEURO MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna

Katowice, , Poland

Centrum Kompleksowej Rehabilitacji

Konstancin-Jeziorna, , Poland

Centrum Opieki Zdrowotnej Orkan Med

Ksawerów, , Poland

Indywidualna Praktyka Lekarska Prof. Konrad Rejdak

Lublin, , Poland

Szpital Kliniczny im Heliodora Swiecickiego Uniwersytetu Medycznego im Karola Marcinkowskiego w Po

Poznan, , Poland

Clinical Research Center sp z o o MEDIC R s k

Poznan, , Poland

NZOZ NEURO KARD Ilkowski i Partnerzy Sp Partnerska Lekarzy

Poznan, , Poland

WroMedica I Bielicka A Strzalkowska s c

Wroclaw, , Poland

Hospital de Braga

Braga, , Portugal

Hospitais da universidade de Coimbra

Coimbra, , Portugal

Hosp. Cuf Descobertas

Lisbon, , Portugal

H. Santo António - Centro Hospitalar do Porto

Porto, , Portugal

Spitalul Universitar de Urgenta Militar Central 'Dr. Carol Davila'

Bucharest, , Romania

Institutul Clinic Fundeni

Bucharest, , Romania

Spitalul Universitar de Urgenta Bucuresti

Bucharest, , Romania

Spitalul Clinic Judetean de Urgenta Pius Brinzeu

Timișoara, , Romania

Barnaul Territorial Clinical Hospital

Barnaul, , Russia

St. Joseph Belgorod Regional Hospital

Belgorod, , Russia

Bryansk Regional Hospital #1

Bryansk, , Russia

Research Medical Center Your Health

Kazan', , Russia

Federal State Budgetary Institution

Krasnoyarsk, , Russia

State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital

Kursk, , Russia

Clinical City Hospital #1

Moscow, , Russia

State Health Care Institution Of Moscow

Moscow, , Russia

Central Clinical Hospital N.A.Semashko

Moscow, , Russia

Municipal Clinical Hospital # 3

Nizhny Novgorod, , Russia

Siberian District Medical Center of Federal Medical-Biological Agency

Novosibirsk, , Russia

Federal Scientific Clinical Center of Physico-Chemical Medicine

Odintsovo, , Russia

Perm State Medical Academy n.a. E. A. Vagner

Perm, , Russia

City Clinical Hospital # 2

Pyatigorsk, , Russia

Municipal Multi-Specialty Hospital # 2

Saint Petersburg, , Russia

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, , Russia

City Clinical Hospital #31

Saint Petersburg, , Russia

Institute of Human Brain Ras

Saint Petersburg, , Russia

City Hospital# 40

Saint Petersburg, , Russia

State Healthcare Institution Samara Regional Clinical Hospital named after V.D.Seredavin

Samara, , Russia

Smolensk Regional Clinical Hospital

Smolensk, , Russia

Siberian State Medical University

Tomsk, , Russia

Tver Regional Clinical Hospital

Tver', , Russia

GUZ Novgorod Regional Clinical Hospital

Veliky Novgorod, , Russia

Yaroslavl Clinical Hospital #8

Yaroslavl, , Russia

Sverdlovsk Region Clinical Hospital #1

Yekaterinburg, , Russia

Clinical Hospital Center Zvezdara

Belgrade, , Serbia

Vojnomedicinska Akademija

Belgrade, , Serbia

University Clinical Center Kragujevac

Kragujevac, , Serbia

University Clinical Center NIS

Niš, , Serbia

Hospital del Mar

Barcelona, , Spain

Hospital Vall d'Hebron

Barcelona, , Spain

Hospital Clinic I Provincial

Barcelona, , Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitario Virgen Macarena

Seville, , Spain

Hospital Vithas Nisa Sevilla

Seville, , Spain

Sahlgrenska Universitetsjukhuset

Gothenburg, , Sweden

Centrum för Neurologi

Stockholm, , Sweden

Karadeniz Teknik University Medical Faculty

Trabzon, , Turkey (Türkiye)

Public Non-profit Enterprise: Chernihiv City Hospital #4 under Chernihiv City Council

Chernihiv, , Ukraine

Municipal health care institution Chernihiv Regional Hospital

Chernihiv, , Ukraine

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, , Ukraine

Limited Liability Company 'Neuro Global'

Ivano-Frankivsk, , Ukraine

Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'

Kharkiv, , Ukraine

Kharkiv Postgrad Academy, Dept of Neurology #1 At Hosp #7

Kharkiv, , Ukraine

National Research Center for Radiation Medicine

Kyiv, , Ukraine

Public Non-Profit Enterprise: Lviv City Clinical Hospital #5

Lviv, , Ukraine

Lviv Clinical Regional Hospital

Lviv, , Ukraine

Odessa National Medical University

Odesa, , Ukraine

ME 'Poltava Regional Clinical Hospital n.a. M.V. Sklifosovsky of the Poltava Regional Council'

Poltava, , Ukraine

Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb

Ternopil, , Ukraine

Medical Center Salutem LLC

Vinnytsia, , Ukraine

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, , Ukraine

Royal Preston Hospital

Preston, , United Kingdom

Salford Royal NHS Foundation Trust

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

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

AC-058B303

Identifier Type: OTHER

Identifier Source: secondary_id

2016-004719-10

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AC-058B303

Identifier Type: -

Identifier Source: org_study_id