A research study to look at the long term benefits and risks of ponesimod 20 mg treatment for patients with relapsing multiple sclerosis.

• Register: EUCTR
• Last refreshed on: 16 October 2017
• Main ID: EUCTR2016-004719-10-ES
• Date of registration: 04/07/2017
• Prospective Registration: Yes
• Primary sponsor: Actelion Pharmaceuticals Ltd.
• Public title: A research study to look at the long term benefits and risks of ponesimod 20 mg treatment for patients with relapsing multiple sclerosis.
• Scientific title: Multicenter, non-comparative extension to study AC-058B301, to investigate the long-term safety, tolerability, and control of disease of ponesimod 20 mg in subjects with relapsing multiple sclerosis - OPTIMUM LT
• Date of first enrolment: 02/10/2017
• Target sample size: 800
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-004719-10
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): yes Therapeutic use (Phase IV): no

Countries of recruitment

Belarus, Bosnia and Herzegovina, Bulgaria, Canada, Croatia, Czech Republic, Finland, France, Georgia, Germany, Greece, Hungary, Israel, Italy, Latvia, Lithuania, Mexico, Poland, Portugal, Romania, Russian Federation, Serbia, Spain, Sweden, Turkey, Ukraine, United Kingdom, United States

Contacts

• Name: clinical trial disclosure desk
• Affiliation: Actelion Pharmaceuticals Ltd.

• Name: clinical trial disclosure desk
• Affiliation: Actelion Pharmaceuticals Ltd.

Key inclusion & exclusion criteria

Inclusion criteria:
1. Signed informed consent, prior to initiation of any study-mandated procedure.
2. Subjects with MS having completed the double-blind treatment in the core study as scheduled (i.e., who completed the double-blind treatment period until Week 108).
3. Compliance with teriflunomide elimination procedure assessed as sufficient by the investigator at visit FU1 or abbreviated visit FU2 of the core study, whichever occurred last.
4. For subjects of reproductive potential:
- Women of childbearing potential (WOCBP):
- must have a negative pre-treatment urine pregnancy test on Day 1;
- must agree to undertake 4-weekly urine pregnancy tests during the study and until 6 weeks after the first of two consecutive tests showing
teriflunomide plasma level < 0.02 mg/L and until at least 30 days after study treatment discontinuation;
- must have been using reliable methods of contraception uninterrupted since EOT in the core study and must agree to continue using reliable
methods of contraception throughout the study until 6 weeks after the first of two consecutive tests showing teriflunomide plasma level
< 0.02 mg/L and until at least 30 days after discontinuation of study treatment.

- Fertile male subjects participating in the study who are sexually active with WOCBP must agree to use a condom until 6 weeks after the first of
two consecutive tests confirming plasma teriflunomide level <0.02 mg/L.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 800
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. Any of the following cardiovascular conditions on Day 1 pre-dose:
a. Resting heart rate (HR) < 50 bpm as measured by the pre-dose 12-lead ECG;
b. Presence of second degree atrioventricular (AV) block or third degree AV block or a QTcF interval > 470 ms (females), > 450 ms (males) on pre-
dose 12-lead ECG;
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:
a. Lymphocyte count: < 0.2 x 109/L (<200/mm3 blinded results);
b. Neutrophil count <1.0 × 109/L(< 1000 cells/mm3);
c. Platelet count < 50 × 109/L (< 50 000 cells/mm3);
d. Creatinine clearance < 30 mL/min (Cockroft-GaultAny findings below)
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:
a. Suspected opportunistic infection of the CNS or any other infection which, in the opinion of the investigator, contraindicates re-start of the study
drug;
b. Stevens-Johnson syndrome or toxic epidermal necrolysis or drug reaction with eosinophilia and systemic symptoms.
7. Need for and intention to administer forbidden studytreatment-concomitant therapy
8. Women who are pregnant or lactating.
9. Male subjects wishing to parent a child any time before the
6 week period following the first of two consecutive tests confirming plasma teriflunomide level <0.02 mg/L;
10. Treatment with any MS Disease Modifying Therapies (DMTs) between core study EOT and first dosing in extension study;
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 from the core study protocol , e.g., uncooperative attitude, inability to return for follow-up visits, or known likelihood of not completing the extension study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

relapsing multiple sclerosis
MedDRA version: 20.0 Level: PT Classification code 10063400 Term: Secondary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 2-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 3-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 4-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 5-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 7-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 8-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: PONESIMOD
Current Sponsor code: ACT-128800
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 9-

Product Name: Ponesimod
Product Code: ACT-128800
Pharmaceutical Form: F

Primary Outcome(s)

Timepoint(s) of evaluation of this end point: NA

Main Objective: Safety objectives:
- To describe the long-term safety and tolerability of ponesimod 20 mg in subjects with RMS.
- To describe the effects of re-initiation of ponesimod treatment after interruption in subjects with RMS.

Efficacy objectives:
- To describe the long term disease control in subjects with RMS receiving ponesimod 20 mg.
- To describe the effect of a switch from teriflunomide to ponesimod 20 mg on disease control in subjects with RMS.

Primary end point(s): The main clinical and MRI-based endpoints are:
- Annualized confirmed relapse rate (ARR; based on the number of confirmed relapses per subject-year);
- Time from core study randomization to first confirmed relapse;
- Time from core baseline to first 12-week confirmed disability accumulation (CDA);
- Time from core baseline to first 24-week confirmed disability accumulation (CDA);
- Percent change from baseline in brain volume (PCBV) at all assessments;
- Cumulative number of combined unique active lesions (CUAL, defined as new Gd+ T1 lesions plus new or enlarging T2 lesions without double-counting the lesions) at all assessments.

Secondary Objective: NA

Secondary Outcome(s)

Secondary end point(s): NA

Timepoint(s) of evaluation of this end point: NA

Secondary ID(s)

AC-058B303

Source(s) of Monetary Support

Actelion Pharmaceuticals Ltd.