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

NCT03232073 | Completed Phase 3 Results FDA Drug

• 2 other identifiers: AC-058B3032016-004719-10
• Study Type: interventional
• Target: 877
• Locations: 27 countries
• Sites: 144

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (34)

• Annualized Confirmed Relapse Rate (ARR)

  ARR: number of confirmed relapses per patient-year. Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours, in the absence of fever or infection. A confirmed relapse is identified when a patient's symptoms worsen as indicated by an increase in their Expanded Disability Status Scale (EDSS) or Functional Systems (FS) scores, consistent with previous clinically stable assessments. Specific criteria for a confirmed relapse include: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0 (normal)-10 (death due to MS).

  From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Time From Core Study Randomization to First Confirmed Relapse

  Time to first confirmed relapse: date of first confirmed relapse (in either core or extension study) minus date of randomization in core study+1 day. Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours in absence of fever or infection. A confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Specific criteria for confirmed relapse are: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0(normal)-10(death due to MS).

  From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Time to First 12-week Confirmed Disability Accumulation (CDA)

  Time to first 12-week CDA is defined as start date of the first 12-week CDA minus date of randomization in the core study + 1 day. A 12-week CDA is defined as a 12-week sustained increase from the core baseline EDSS score, which is confirmed at a scheduled visit after 12-weeks. CDA is defined as: (a) Sustained increase of at least 1.5 in EDSS for participants with a core baseline EDSS score of 0; (b) Sustained increase of at least 1.0 in EDSS for participants with a core baseline EDSS score of 1.0 to 5.0; (c) Sustained increase of at least 0.5 in EDSS for participants with a core baseline EDSS score \>=5.5, confirmed after 12 weeks. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Time to First 24-week Confirmed Disability Accumulation (CDA)

  Time to first 24-week CDA was defined as start date of the first 24-week CDA minus date of randomization in the core study + 1 day. A 24-week CDA was defined as a 24-week sustained increase from the core baseline EDSS score, which is confirmed at a scheduled visit after 24-weeks. CDA was defined as: (a) Sustained increase of at least 1.5 in EDSS for participants with a core baseline EDSS score of 0; (b) Sustained increase of at least 1.0 in EDSS for participants with a core baseline EDSS score of 1.0 to 5.0; (c) Sustained increase of at least 0.5 in EDSS for participants with a core baseline EDSS score \>=5.5, confirmed after 24 weeks. EDSS was an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Percentage of Participants With Absence of Relapses

  Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours in absence of fever or infection. A confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Specific criteria for confirmed relapse: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0(normal)-10(death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Change From Baseline in Expanded Disability Status Scale (EDSS)

  EDSS is ordinal clinical rating scale based on standard neurological examination for assessing neurological disability and impairment in MS. Seven FS scores were rated on a scale ranged from 0 to 5 or 6 to assess visual, brain, stem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral functions while ambulation was scored on scale ranged from 0 to 12 to assess walking distance and assistance. Individual FS scores were then used in conjugation with ambulation score to obtain EDSS score which ranged from 0 (normal) to 10 (death due to MS) in 0.5 unit increments that represented higher levels of disability. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Three Components (NEDA-3) at Extension End of Study

  NEDA-3 up to extension EOS is defined by the absence of confirmed relapse, gadolinium-enhancing (Gd+ T1) lesions, new or enlarging T2 lesions, and 12-week CDA. If at least one of the criteria was not fulfilled or the participant discontinued treatment prematurely, the participant was not considered to have achieved NEDA-3. Confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging: 0 (normal)-10 (death due to MS). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Four Components (NEDA-4) at Extension End of Study

  NEDA-4 up to EOS is defined by the absence of confirmed relapse, Gd+ T1 lesions, new or enlarging T2 lesions, 12-week CDA until EOS, and absence of annual brain volume decrease \>=0.4% from core baseline up to extension EOS. If at least one of the criteria was not fulfilled or the participant discontinued treatment prematurely, the participant was not considered to have achieved NEDA-4. Confirmed relapse: when patient's symptoms worsen by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging: 0 (normal)-10 (death due to MS). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in core study for each outcome measure and each participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Percent Change From Baseline in Brain Volume (PCBV) Measured by Magnetic Resonance Imaging (MRI)

  Percent change from baseline in brain volume (PCBV) measured by MRI were reported. Normalized Brain Volume at core baseline was measured in cubic centimeter (cm\^3). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

  From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

• Cumulative Number of Combined Unique Active Lesions (CUAL) Measured by MRI

  CUALs was calculated as sum of new T1 Gadolinium-enhanced (Gd+) lesions and new or enlarging T2 lesions (without double-counting of lesions) from baseline up to extension EOS based on the Magnetic resonance imaging (MRI). Average number of lesions per patient-year were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Number of Gadolinium-enhancing (Gd+) T1 Lesions Measured by MRI

  Number of Gd+ T1 lesions measured by MRI were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. For this outcome measure, results presented here are for the Extension end-of-treatment visit.

  From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

• Cumulative Number of New or Enlarging T2 Lesions Measured by MRI

  Cumulative number of new or enlarging T2 lesions measured by MRI were reported. Average number of lesions per year were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

  From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

• Change From Baseline in Volume of MRI Lesions (T2 Lesions and T1 Hypointense Lesions)

  Change from baseline in volume of MRI lesions (T2 lesions, T1 hypointense lesions) were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

  From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

• Number of Participants With Absence of MRI Lesions (Gd+ T1 Lesions, New or Enlarging T2 Lesions)

  Number of participants with absence of MRI lesions (Gd+ T1 lesions, new or enlarging T2 lesions) were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

  From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

• Percentage of Gd+ Lesions at Baseline Evolving to Persistent Black Holes (PBHs)

  Percentage of Gd+ lesions at baseline evolving to PBHs were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

  From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

• Number of Participants With Treatment-emergent Adverse Events (TEAEs)

  Number of participants with TEAEs were reported. An AE is any untoward medical event that occurs in a participants being administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs occurring from start of treatment up to treatment end date + 15 days.

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With Treatment-emergent New Morphological Electrocardiogram (ECG) Abnormalities

  Number of participants with treatment-emergent new morphological ECG abnormalities were reported. Treatment-emergent new morphological ECG abnormalities are defined as those ECG abnormalities occurring from start of treatment up to treatment end date + 15 days.

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Actual Values of 12-lead ECG Measurements up to End of Study Treatment: Heart Rate

  Actual values of 12-lead ECG measurements up to end of study treatment: heart rate were reported. In this outcome measure, results were presented for extension end of treatment visit.

  From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Actual Values of 12-lead ECG Measurements up to End of Study Treatment: PR, QRS, QT, QTcB, QTcF

  Actual values of 12-lead ECG measurements up to end of study treatment: PR, QRS, QT, QTcB, QTcF were reported. In this outcome measure, results were presented for extension end of treatment visit.

  From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Change in Heart Rate (HR) From Baseline up to End of Study Treatment

  Change in heart rate (HR) from baseline up to end of study treatment were reported.

  From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Change in PR, QRS, QT, QTcB, QTcF From Baseline up to End of Study Treatment

  Change in PR, QRS, QT, QTcB, QTcF from baseline up to end of study treatment were reported.

  From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Absolute Values in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) Values

  Absolute values in FEV1 and FVC values were reported. FEV1: the maximal volume of air exhaled from the lungs in 1 second of a forced expiration from a position of full inspiration as measured by spirometer. FVC: the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. Results are presented for extension end of treatment visit.

  From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Percent Change in (FEV1) and Forced Vital Capacity (FVC) From Baseline (%)

  Percent change in FEV1 and FVC from baseline (%) were reported. FEV1: the maximal volume of air exhaled from the lungs in 1 second of a forced expiration from a position of full inspiration as measured by spirometer. FVC: the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. In this outcome measure, results were presented for extension end of treatment visit.

  From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)

  Number of participants with treatment-emergent SAEs were reported. A SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or was an important medical event. Treatment-emergent SAEs are defined as SAEs occurring from start of treatment up to treatment end date + 15 days.

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)

  Number of participants with treatment-emergent AESIs were reported. AESIs included bradyarrhythmia occurred post-first dose, macular edema, bronchoconstriction, severe liver injury, serious opportunistic infections including progressive multifocal leukoencephalopathy (PML), skin cancer, non-skin malignancy, convulsions, unexpected neurological or psychiatric symptoms/signs (posterior reversible encephalopathy syndrome \[PRES\], acute disseminated encephalomyelitis \[ADEM\], and atypical MS relapses). Treatment-emergent AESIs are defined as AESIs occurring from start of treatment up to treatment end date + 15 days.

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With AE Leading to Premature Discontinuation of Study Treatment

  Number of participants with AE leading to premature discontinuation of study treatment were reported. An AE is any untoward medical event that occurs in a participant being administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs occurring from start of treatment up to treatment end date + 15 days.

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With Treatment-emergent Decrease From Baseline >20% and >30% in FEV1 or FVC

  Number of participants with treatment-emergent decrease from baseline \>20% and \>30% in FEV1 or FVC were reported. Treatment-emergent is defined as events occurring from start of treatment up to treatment end date + 15 days (that is, findings not present at any assessment prior to first treatment in the extension study).

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With Treatment-emergent Decrease of >20% Points in Percent Predicted FEV1 and FVC From Baseline

  Number of participants with treatment-emergent decrease of \>20% points in percent predicted FEV1 and FVC from baseline were reported. Treatment-emergent is defined as events occurring from start of treatment up to treatment end date + 15 days (that is, findings not present at any assessment prior to first treatment in the extension study).

  From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

• Number of Participants With a Decrease of >=200 mL or >=12% in FEV1 or FVC From Baseline to EOT

  Number of participants with a decrease of \>=200 mL or \>=12% in FEV1 or FVC from baseline to EOT were planned to be reported. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. This endpoint is not relevant as a substantial proportion of patients continued onto post-treatment disease-modifying therapy (DMT), hence it cannot provide an assessment of reversibility.

  From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Change in FEV1 and FVC (% Predicted) From Baseline to End of Treatment (EOT)

  Change in FEV1 and FVC (% predicted) from baseline to EOT were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

  From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Change in FEV1 and FVC (% Predicted) From Baseline to End of Study (EOS)

  Change in FEV1 and FVC (% predicted) from baseline to EOS were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

  From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

• Absolute Change in Lung Diffusion Capacity as Assessed by Diffusing Capacity for the Lungs Measured Using Carbon Monoxide (DL[CO]) From Baseline

  Absolute change in lung diffusion capacity as assessed by DL\[CO\] from baseline were reported. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

  From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

• Change in DL[CO] (% Predicted) From Baseline to EOT

  Change in DL\[CO\] (% predicted) from baseline to EOT were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

  From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

• Change in DL[CO] (% Predicted) From Baseline to EOS

  Change in DL\[CO\] (% predicted) from baseline to EOS were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

  From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

Other Outcomes (2)

• Actual Values of 12-lead ECG Measurements on Day of First Re-initiation (Day 1) of Study Drug: Heart Rate

  Extension analysis period: Predose, 1, 2, 3, 4 hours post dose on Day 1 of re-initiation (re-initiation could occur on any day during the treatment period when drug was interrupted for at least 3 consecutive days [up to 71.8 months])

• Actual Values of 12-lead ECG Measurements on Day of First Re-initiation (Day 1) of Study Drug: PR, QRS, QT, QTcB, QTcF

  Extension analysis period: Predose, 1, 2, 3, 4 hours post dose on Day 1 of re-initiation (re-initiation could occur on any day during the treatment period when drug was interrupted for at least 3 consecutive days [up to 71.8 months])

Study Arms (1)

Ponesimod

EXPERIMENTAL

20 mg administered orally once daily

Drug: Ponesimod

Interventions

Ponesimod 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

Ponesimod

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• Subjects with MS having completed the double-blind treatment in the core study as scheduled
• Compliance with teriflunomide elimination procedure
• 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.

You may not qualify if:

• Any of the following cardiovascular conditions on Day 1 pre-dose:
• Resting heart rate (HR) \< 50 bpm;
• Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval \> 470 ms (females), \> 450 ms (males);
• 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:
• Lymphocyte count: \< 0.2 x 109/L;
• Neutrophil count \<1.0 × 109/L;
• Platelet count \< 50 × 109/L;
• Creatinine clearance \< 30 mL/min
• At Visit 14 of the core study (EOT) \>30% decrease from core study baseline FEV1 and/or FVC;
• Clinically significant, persistent respiratory AEs (e.g., dyspnea) not resolved prior to first dosing in the extension study.
• Macular edema at any time between Visit 1 (Screening) in the core study and Day 1 of the extension study.
• 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:
• Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study drug;
• Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.
• Need for and intention to administer forbidden study treatment-concomitant therapy

Sponsors & Collaborators

• Actelion: lead

Study Sites (148)

The Research Center of Southern California, LLC

Carlsbad, California, 92011, United States

Location

The Neurology Group

Pomona, California, 91767, United States

Location

Mountain View Clinical Research

Denver, Colorado, 80209, United States

Location

Neurology Associates of Ormond Beach

Ormond Beach, Florida, 32174, United States

Location

University of South Florida

Tampa, Florida, 33612, United States

Location

Josephson Wallack Munshower Neurology, PC

Indianapolis, Indiana, 46256, United States

Location

Raleigh Neurology Associates

Raleigh, North Carolina, 27607, United States

Location

Ohio Health

Columbus, Ohio, 43214, United States

Location

Advanced Neurosciences Institute

Franklin, Tennessee, 37064, United States

Location

Grodno University Hospital

Grodno, 230017, Belarus

Location

Minsk City Clinical Hospital 5

Minsk, 220026, Belarus

Location

Republican Scientific Clinical Centre

Minsk, 220114, Belarus

Location

Vitebsk Regional Diagnostic Center

Vitebsk, 210023, Belarus

Location

Vitebsk Regional Clinical Hospital

Vitebsk, 210037, Belarus

Location

University Clinicl Center Sarajevo

Sarajevo, 71000, Bosnia and Herzegovina

Location

UMHAT Sveti Georgi

Plovdiv, 4002, Bulgaria

Location

Multiprofile Hospital for Active Treatment in Neurology and Psychiatry Sveti Naum

Sofia, 1113, Bulgaria

Location

Multiprofile Hospital For Active Treatment National Cardiology Hospital, Ead

Sofia, 1309, Bulgaria

Location

Acibadem City Clinic Tokuda Hospital

Sofia, 1407, Bulgaria

Location

St Ivan Rilski University Multiprofile Hospital For Active Treatment

Sofia, 1431, Bulgaria

Location

University Multiprofile Hospital for Active Treatment Alexandrovska EAD

Sofia, 1431, Bulgaria

Location

Military Medical Academy Multiprofile Hospital for Active Treatment Sofia

Sofia, 1606, Bulgaria

Location

University of Alberta

Edmonton, Alberta, T6G 1Z1, Canada

Location

Royal Jubilee Hospital

Victoria, British Columbia, V8R 1J8, Canada

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Recherche Sepmus Inc.

Greenfield Park, Quebec, J4V 2J2, Canada

Location

Ch Osijek

Osijek, 31000, Croatia

Location

University Hospital Center Zagreb

Zagreb, 10000, Croatia

Location

Fakultní nemocnici Brno

Brno, 65691, Czechia

Location

Fakultni nemocnice Hradec Kralove

Hradec Králové, 500 05, Czechia

Location

Nemocnice Jihlava

Jihlava, 586 33, Czechia

Location

Fakultni Nemocnice Ostrava

Ostrava-Poruba, 708 52, Czechia

Location

Pardubicka krajska nemocnice a s

Pardubice, 532 03, Czechia

Location

Vseobecna Fakultní Nemocnice

Prague, 128 08, Czechia

Location

FN Motol

Prague, 150 06, Czechia

Location

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

Teplice, 415 29, Czechia

Location

Suomen Terveystalo Tampere

Tampere, 33100, Finland

Location

Mehilainen NEO

Turku, 20520, Finland

Location

Hopital Pellegrin CHU Bordeaux

Bordeaux, 33076, France

Location

CHU Clermont-Ferrand - Hopital Gabriel Montpied

Clermont-Ferrand, 63003, France

Location

Hopital Nord Laennec CHU NANTES

Nantes, 44093, France

Location

Hopital PASTEUR

Nice, 6000, France

Location

Nouvel Hopital Civil

Strasbourg, 67091, France

Location

LTD 'Aversi Clinic'

Tbilisi, 0160, Georgia

Location

P. Sarajishvili Institute of Neurology

Tbilisi, 112, Georgia

Location

Pineo Medical Ecosystem Ltd

Tbilisi, 114, Georgia

Location

S.Khechinashvili University Hospital

Tbilisi, 179, Georgia

Location

Curatio, Jsc

Tbilisi, 186, Georgia

Location

Universitätsklinikum Carl-Gustav-Carus Dresden

Dresden, 1307, Germany

Location

Helios Klinikum Erfurt

Erfurt, 99089, Germany

Location

Panakeia - Arzneimittelforschung GmbH

Leipzig, 04275, Germany

Location

Universitatsmedizin der Johannes Gutenberg Universitat Mainz

Mainz, 55131, Germany

Location

401 Military Hospital

Athens, 115 25, Greece

Location

Naval Hospital of Athens

Athens, 11521, Greece

Location

Medical Center of Athens

Marousi, 15125, Greece

Location

Uzsoki Utcai Korhaz

Budapest, 1145, Hungary

Location

Jahn Ferenc Del-pesti Korhaz es Rendelointezet

Budapest, 1204, Hungary

Location

Valeomed EGÉSZSÉGÜGYI KÖZPONT

Esztergom, 2500, Hungary

Location

Petz Aladar Megyei Oktato Korhaz

Győr, 9023, Hungary

Location

Kistarcsai Flor Ferenc Korhaz

Kistarcsa, 2143, Hungary

Location

Barzilai Medical Center

Ashkelon, 7830604, Israel

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Hadassah Medical Center

Jerusalem, 9112001, Israel

Location

Ziv Medical Center

Safed, 1304300, Israel

Location

Ospedale San Salvatore

L’Aquila, 67100, Italy

Location

Azienda Ospedaliera Sant Andrea

Roma, 189, Italy

Location

Pauls Stradins Clinical University Hospital

Riga, 1002, Latvia

Location

Latvias Juras medicinas centrs Ltd

Riga, 1015, Latvia

Location

Rīgas Austrumu klīniskā universitātes slimnīca

Riga, LV-1038, Latvia

Location

Hospital of Lithuanian University of Health Sciences Kaunas Clinics

Kaunas, LT50161, Lithuania

Location

VsI Respublikine Siauliu ligonine, V.

Šiauliai, 76231, Lithuania

Location

Unidad de Investigacion En Salud

Chihuahua City, 31203, Mexico

Location

CRI Centro Regiomontano de Investigacion SC

Nuevo León, 64060, Mexico

Location

Neurocentrum Bydgoszcz Sp Z O O

Bydgoszcz, 85 796, Poland

Location

Copernicus Podmiot Leczniczy Sp. z o.o

Gdansk, 80-803, Poland

Location

Neuro Centrum Centrum Terapii SM

Katowice, 40 571, Poland

Location

NEURO MEDIC Janusz Zbrojkiewicz Poradnia Wielospecjalistyczna

Katowice, 40 686, Poland

Location

Centrum Kompleksowej Rehabilitacji

Konstancin-Jeziorna, 05 510, Poland

Location

Centrum Opieki Zdrowotnej Orkan Med

Ksawerów, 95 054, Poland

Location

Indywidualna Praktyka Lekarska Prof. Konrad Rejdak

Lublin, 20-410, Poland

Location

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

Poznan, 60 355, Poland

Location

Clinical Research Center sp z o o MEDIC R s k

Poznan, 61 731, Poland

Location

NZOZ NEURO KARD Ilkowski i Partnerzy Sp Partnerska Lekarzy

Poznan, 61 853, Poland

Location

WroMedica I Bielicka A Strzalkowska s c

Wroclaw, 51 685, Poland

Location

Hospital de Braga

Braga, 4710-243, Portugal

Location

Hospitais da universidade de Coimbra

Coimbra, 3000-075, Portugal

Location

Hosp. Cuf Descobertas

Lisbon, 1998-018, Portugal

Location

H. Santo António - Centro Hospitalar do Porto

Porto, 4099-001, Portugal

Location

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

Bucharest, 10825, Romania

Location

Institutul Clinic Fundeni

Bucharest, 22328, Romania

Location

Spitalul Universitar de Urgenta Bucuresti

Bucharest, 50098, Romania

Location

Spitalul Clinic Judetean de Urgenta Pius Brinzeu

Timișoara, 300723, Romania

Location

Barnaul Territorial Clinical Hospital

Barnaul, 656024, Russia

Location

St. Joseph Belgorod Regional Hospital

Belgorod, 308007, Russia

Location

Bryansk Regional Hospital #1

Bryansk, 241033, Russia

Location

Research Medical Center Your Health

Kazan', 420097, Russia

Location

Federal State Budgetary Institution

Krasnoyarsk, 660037, Russia

Location

State Budgetary Healthcare Institution Kursk Region Kursk Regional Clinical Hospital

Kursk, 305007, Russia

Location

Clinical City Hospital #1

Moscow, 117049, Russia

Location

State Health Care Institution Of Moscow

Moscow, 127015, Russia

Location

Central Clinical Hospital N.A.Semashko

Moscow, 129128, Russia

Location

Municipal Clinical Hospital # 3

Nizhny Novgorod, 603155, Russia

Location

Siberian District Medical Center of Federal Medical-Biological Agency

Novosibirsk, 630007, Russia

Location

Federal Scientific Clinical Center of Physico-Chemical Medicine

Odintsovo, 143000, Russia

Location

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

Perm, 614990, Russia

Location

City Clinical Hospital # 2

Pyatigorsk, 357538, Russia

Location

Municipal Multi-Specialty Hospital # 2

Saint Petersburg, 194354, Russia

Location

Pavlov First Saint Petersburg State Medical University

Saint Petersburg, 197022, Russia

Location

City Clinical Hospital #31

Saint Petersburg, 197110, Russia

Location

Institute of Human Brain Ras

Saint Petersburg, 197376, Russia

Location

City Hospital# 40

Saint Petersburg, 197706, Russia

Location

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

Samara, 443095, Russia

Location

Smolensk Regional Clinical Hospital

Smolensk, 214018, Russia

Location

Siberian State Medical University

Tomsk, 634050, Russia

Location

Tver Regional Clinical Hospital

Tver', 170036, Russia

Location

GUZ Novgorod Regional Clinical Hospital

Veliky Novgorod, 214018, Russia

Location

Yaroslavl Clinical Hospital #8

Yaroslavl, 150003, Russia

Location

Sverdlovsk Region Clinical Hospital #1

Yekaterinburg, 620102, Russia

Location

Clinical Hospital Center Zvezdara

Belgrade, 11000, Serbia

Location

Vojnomedicinska Akademija

Belgrade, 11000, Serbia

Location

University Clinical Center Kragujevac

Kragujevac, 34000, Serbia

Location

University Clinical Center NIS

Niš, 18000, Serbia

Location

Hospital del Mar

Barcelona, 8003, Spain

Location

Hospital Vall d'Hebron

Barcelona, 8035, Spain

Location

Hospital Clinic I Provincial

Barcelona, 8036, Spain

Location

Hospital Universitario de La Princesa

Madrid, 28006, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

Location

Hospital Vithas Nisa Sevilla

Seville, 41950, Spain

Location

Sahlgrenska Universitetsjukhuset

Gothenburg, 413 45, Sweden

Location

Centrum för Neurologi

Stockholm, 113 65, Sweden

Location

Karadeniz Teknik University Medical Faculty

Trabzon, 61080, Turkey (Türkiye)

Location

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

Chernihiv, 14001, Ukraine

Location

Municipal health care institution Chernihiv Regional Hospital

Chernihiv, 14029, Ukraine

Location

Ivano-Frankivsk Regional Clinical Hospital

Ivano-Frankivsk, 76018, Ukraine

Location

Limited Liability Company 'Neuro Global'

Ivano-Frankivsk, 76493, Ukraine

Location

Kharkiv Railway Clinical Hospital N1 Of Brance 'Health Center'

Kharkiv, 61103, Ukraine

Location

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

Kharkiv, 61176, Ukraine

Location

National Research Center for Radiation Medicine

Kyiv, 3115, Ukraine

Location

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

Lviv, 79000, Ukraine

Location

Lviv Clinical Regional Hospital

Lviv, 79010, Ukraine

Location

Odessa National Medical University

Odesa, 65009, Ukraine

Location

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

Poltava, 36024, Ukraine

Location

Mnce 'Ternopil Regional Clinical Psychoneurology Hospital' of Trb

Ternopil, 46027, Ukraine

Location

Medical Center Salutem LLC

Vinnytsia, 21000, Ukraine

Location

O.F. Herbachevskyi Regional Clinical Hospital

Zhytomyr, 10008, Ukraine

Location

Royal Preston Hospital

Preston, PR2 9HT, United Kingdom

Location

Salford Royal NHS Foundation Trust

Salford, M6 8HD, United Kingdom

Location

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

ponesimod

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

Due to limited availability of COVID-19 vaccine-naïve MS patients, the COVID-19 vaccination sub-study was cancelled and removed from the protocol after implementation of amendment 5.

Results Point of Contact

• Title: Associate Director Clinical Sciences Neuro
• Organization: Actelion Pharmaceuticals Ltd

ClinicalTrialDisclosure@its.jnj.com

844-434-4210

Study Officials

• Tatiana Sidorenko, 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: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-group open-label extension study to investigate long-term safety, tolerability and control of disease of ponesimod 20 mg in subjects with RMS. Statistical analyses will be descriptive and therefore all endpoints are exploratory in nature. All exploratory endpoints are listed under primary outcomes.

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 27, 2017
• Study Start: July 5, 2017
• Primary Completion: January 16, 2024
• Study Completion: January 16, 2024
• Last Updated: June 22, 2025
• Results First Posted: February 21, 2025

Record last verified: 2025-06

Locations

DE (4); PT (4); LI (2); GB (2); BU (7); BE (5); RO (4); BO (1); FI (2); GE (5); FR (5); IT (2); SE (2); TU (1); CA (4); GR (3); HU (5); CR (2); LA (3); ME (2); RU (26); ES (7); UA (14); CZ (8); IL (4); US (9); PL (11)