Phase 3
N=877
Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple Sclerosis
Multiple Sclerosis
Bottom Line
View on ClinicalTrials.gov: NCT03232073 ↗Enrolled (actual)
877
Serious AEs
12.9%
Results posted
Feb 2025
Primary outcome: Primary: Annualized Confirmed Relapse Rate (ARR) — 0.143; 0.184 relapses per patient-year
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Ponesimod (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Actelion
- Primary completion
- Jan 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Annualized Confirmed Relapse Rate (ARR) |
0.143; 0.184 | — |
| PRIMARY Time From Core Study Randomization to First Confirmed Relapse |
402.71; NA | — |
| PRIMARY Time to First 12-week Confirmed Disability Accumulation (CDA) |
NA; NA | — |
| PRIMARY Time to First 24-week Confirmed Disability Accumulation (CDA) |
NA; NA | — |
| PRIMARY Percentage of Participants With Absence of Relapses |
56.7; 51.6 | — |
| PRIMARY Change From Baseline in Expanded Disability Status Scale (EDSS) |
0.16; 0.34 | — |
| PRIMARY Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Three Components (NEDA-3) at Extension End of Study |
17.5; 7.5 | — |
| PRIMARY Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Four Components (NEDA-4) at Extension End of Study |
5.2; 2.3 | — |
| PRIMARY Percent Change From Baseline in Brain Volume (PCBV) Measured by Magnetic Resonance Imaging (MRI) |
-2.52; -2.72 | — |
| PRIMARY Cumulative Number of Combined Unique Active Lesions (CUAL) Measured by MRI |
1.352; 1.954 | — |
| PRIMARY Number of Gadolinium-enhancing (Gd+) T1 Lesions Measured by MRI |
0.211; 0.395 | — |
| PRIMARY Cumulative Number of New or Enlarging T2 Lesions Measured by MRI |
1.352; 1.951 | — |
| PRIMARY Change From Baseline in Volume of MRI Lesions (T2 Lesions and T1 Hypointense Lesions) |
-435.7; 91.5; 165.6; 309.4 | — |
| PRIMARY Number of Participants With Absence of MRI Lesions (Gd+ T1 Lesions, New or Enlarging T2 Lesions) |
293; 236; 152; 101 | — |
| PRIMARY Percentage of Gd+ Lesions at Baseline Evolving to Persistent Black Holes (PBHs) |
22.3; 25.1 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) |
411; 410 | — |
| PRIMARY Number of Participants With Treatment-emergent New Morphological Electrocardiogram (ECG) Abnormalities |
153; 140 | — |
| PRIMARY Actual Values of 12-lead ECG Measurements up to End of Study Treatment: Heart Rate |
67.4; 67.6 | — |
| PRIMARY Actual Values of 12-lead ECG Measurements up to End of Study Treatment: PR, QRS, QT, QTcB, QTcF |
150.0; 153.3; 92.1; 93.3; 392.5; 391.0 | — |
| PRIMARY Change in Heart Rate (HR) From Baseline up to End of Study Treatment |
-1.7; -1.5 | — |
| PRIMARY Change in PR, QRS, QT, QTcB, QTcF From Baseline up to End of Study Treatment |
0.5; 2.0; -0.4; 2.9; 7.8; 8.9 | — |
| PRIMARY Absolute Values in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) Values |
3.01; 3.08; -3.96; 4.04 | — |
| PRIMARY Percent Change in (FEV1) and Forced Vital Capacity (FVC) From Baseline (%) |
-7.96; -6.75; -5.09; -3.93 | — |
| PRIMARY Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) |
56; 57 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs) |
11; 13; 5; 5; 31; 25 | — |
| PRIMARY Number of Participants With AE Leading to Premature Discontinuation of Study Treatment |
34; 41 | — |
| PRIMARY Number of Participants With Treatment-emergent Decrease From Baseline >20% and >30% in FEV1 or FVC |
80; 82; 18; 21; 54; 60 | — |
| PRIMARY Number of Participants With Treatment-emergent Decrease of >20% Points in Percent Predicted FEV1 and FVC From Baseline |
70; 68; 59; 57 | — |
| PRIMARY Number of Participants With a Decrease of >=200 mL or >=12% in FEV1 or FVC From Baseline to EOT |
— | — |
| PRIMARY Change in FEV1 and FVC (% Predicted) From Baseline to End of Treatment (EOT) |
-7.14; -5.43; -4.70; -3.19 | — |
| PRIMARY Change in FEV1 and FVC (% Predicted) From Baseline to End of Study (EOS) |
-5.95; -4.08; -4.48; -1.98 | — |
| PRIMARY Absolute Change in Lung Diffusion Capacity as Assessed by Diffusing Capacity for the Lungs Measured Using Carbon Monoxide (DL[CO]) From Baseline |
0.7; 0.1 | — |
| PRIMARY Change in DL[CO] (% Predicted) From Baseline to EOT |
5.7; -9.4 | — |
| PRIMARY Change in DL[CO] (% Predicted) From Baseline to EOS |
9.3; 2.2 | — |
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.
Eligibility Criteria
Inclusion Criteria
- 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.
Exclusion Criteria
- Any of the following cardiovascular conditions on Day 1 pre-dose:
- Resting heart rate (HR) 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: 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
- Women who are pregnant or lactating.
- Male subjects wishing to parent a child;
- Treatment with any MS Disease Modifying Therapies;
- 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;
- Subjects unlikely to comply with the extension study protocol based on investigator best judgment
Data sourced from ClinicalTrials.gov (NCT03232073). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.