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

Multicenter, Randomized, Double-blind, Parallel-group Extension to Study AC-058B201 to Investigate the Long-term Safety, Tolerability, and Efficacy of Three Doses of Ponesimod, an Oral S1P1 Receptor Agonist, in Patients With Relapsing-remitting Multiple Sclerosis

This study is an extension to the study AC-058B201 and will investigate the long-term safety, tolerability and efficacy of ponesimod in patients with relapsing-remitting multiple sclerosis.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Drug: Ponesimod 10 mg; Drug: Ponesimod 20 mg; Drug: Ponesimod 40 mg

• Study Type: Interventional
• Enrollment (Actual): 353
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Vienna, Austria
• Bulgaria
  • Sofia, Bulgaria
• Canada
  • Ontario
    • Ottawa, Ontario, Canada
• Czechia
  • Brno, Czechia
  • Jihlava, Czechia
  • Olomouc, Czechia
  • Ostrava-Poruba, Czechia
  • Praha 2, Czechia
  • Teplice, Czechia
• Finland
  • Helsinki, Finland
  • Hyvinkää, Finland
  • Tampere, Finland
  • Turku, Finland
• France
  • Montpellier Cedex 5, France
• Germany
  • Berlin, Germany
  • Essen, Germany
  • Ulm, Germany
• Hungary
  • Budapest, Hungary
  • Esztergom, Hungary
  • Győr, Hungary
  • Miskolc, Hungary
• Israel
  • Tel-Hashomer, Israel
  • Zerifin, Israel
• Netherlands
  • Breda, Netherlands
• Poland
  • Katowice, Poland
  • Poznan, Poland
  • Warszawa, Poland
  • Wroclaw, Poland
• Romania
  • Cluj-Napoca, Romania
  • Timisoara, Romania
• Russian Federation
  • Kazan, Russian Federation
  • Moscow, Russian Federation
  • Nizhniy Novgorod, Russian Federation
  • Pyatigorsk, Russian Federation
  • Saint Petersburg, Russian Federation
  • Samara, Russian Federation
  • Saratov, Russian Federation
  • St. Petersburg, Russian Federation
  • UFA, Russian Federation
• Serbia
  • Belgrade, Serbia
  • Kragujevac, Serbia
  • Nis, Serbia
• Spain
  • Majadahonda, Spain
  • Malaga, Spain
  • Sevilla, Spain
• Sweden
  • Göteborg, Sweden
  • Stockholm, Sweden
  • Umeå, Sweden
• Switzerland
  • Lugano, Switzerland
• Ukraine
  • Chernihiv, Ukraine
  • Dnipropetrovsk, Ukraine
  • Kyiv, Ukraine
  • Odesa, Ukraine
• United Kingdom
  • Bristol, United Kingdom
  • London, United Kingdom
  • Plymouth, United Kingdom
• United States
  • Arizona
    • Phoenix, Arizona, United States
    • Scottsdale, Arizona, United States
  • California
    • Palo Alto, California, United States
    • Sacramento, California, United States
  • Florida
    • Venice, Florida, United States
  • Indiana
    • Indianapolis, Indiana, United States
  • Kansas
    • Kansas City, Kansas, United States
    • Lenexa, Kansas, United States
  • New York
    • Latham, New York, United States
    • Schenectady, New York, United States
    • Stony Brook, New York, United States
  • North Carolina
    • Raleigh, North Carolina, United States
  • Ohio
    • Cincinnati, Ohio, United States
    • Columbus, Ohio, United States
  • Vermont
    • Burlington, Vermont, United States
  • Washington
    • Kirkland, Washington, United States

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Patients who completed study treatment at their regular Week 24 (End of treatment) visit within the core study AC-058B201.
2. Signed informed consent for participating in the extension study.

Exclusion Criteria:

1. Any clinically relevant medical or surgical condition, which, in the opinion of the investigator, would put the patient at risk by participating in the extension study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ponesimod 10 mg; Ponesimod 10 mg oral use	Drug: Ponesimod 10 mg; Ponesimod 10 mg oral use
Experimental: Ponesimod 20 mg; Ponesimod 20 mg oral use	Drug: Ponesimod 20 mg; Ponesimod 20 mg oral use
Experimental: Ponesimod 40 mg; Ponesimod 40 mg oral use	Drug: Ponesimod 40 mg; Ponesimod 40 mg oral use

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Annualized Relapse Rate (ARR) of Confirmed Relapses	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).	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
Time to First Confirmed Relapse	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).	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
Time to 24 Weeks Confirmed Disability Progression	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).	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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With at Least One Treatment-emergent Serious Adverse Events (SAEs)	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.	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

Collaborators and Investigators

• Sponsor: Actelion

Study record dates

Study Major Dates

• Study Start (Actual): May 12, 2010
• Primary Completion (Actual): September 6, 2023
• Study Completion (Actual): September 6, 2023

Study Registration Dates

• First Submitted: March 24, 2010
• First Submitted That Met QC Criteria: March 24, 2010
• First Posted (Estimated): March 25, 2010

Study Record Updates

• Last Update Posted (Actual): March 30, 2025
• Last Update Submitted That Met QC Criteria: March 28, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pathologic Processes; Autoimmune Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Multiple Sclerosis; Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sphingosine 1 Phosphate Receptor Modulators; Immunosuppressive Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Ponesimod
• Other Study ID Numbers: AC-058B202; 2009-011470-15 (EudraCT Number)