Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple Sclerosis

Multiple Sclerosis Clinical Trial

— OPTIMUM  

Official title:

Multicenter, Randomized, Double-blind, Parallel-group, Active-controlled, Superiority Study to Compare the Efficacy and Safety of Ponesimod to Teriflunomide in Subjects With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02425644
• Other study ID #: AC-058B301
• Secondary ID: 2012-000540-10
• Status: Completed
• Phase: Phase 3
• Start date: June 4, 2015
• Est. completion date: May 16, 2019

Study information

• Verified date: January 2023
• Source: Actelion
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

International clinical trial to compare ponesimod and teriflunomide in relapsing multiple sclerosis

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1133
• Est. completion date: May 16, 2019
• Est. primary completion date: May 16, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Male and female subjects aged 18 to 55 years with established diagnosis of MS McDonald 2010 with relapsing course from onset (i.e., RRMS and SPMS with superimposed relapses).

Subjects must have active disease evidenced by one or more MS attacks with onset within the period of 12 to 1 months prior to randomization, or by two or more MS attacks with onset within the 24 to 1 months prior to randomization, or with one or more gadolinium-enhancing (Gd+) lesion(s) of the brain on an MRI performed within 6 months prior to randomization.

Enrolled subjects must be ambulatory (EDSS score of up to 5.5 inclusive) and may be treatment-naïve or previously treated with MS disease modifying therapy.

Exclusion Criteria:

Subjects with significant medical conditions or therapies for such conditions (e.g., cardiovascular, pulmonary, immunological, hepatic,ophthalmological conditions) or lactating or pregnant women are not eligible to enter the study.

Subjects with contraindications to MRI or with clinically relevant medical or surgical conditions that, in the opinion of the investigator, would put the subject at risk by participating in the study are not eligible to enter the study.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• ponesimod
film-coated tablet with 20 mg ponesimod, administered orally once daily in the morning
• teriflunomide
film-coated tablet with 14 mg teriflunomide, administered orally once daily in the morning

Locations

Country	Name	City	State
Belarus	Investigator Site 3605	Grodno
Belarus	Investigator Site 3602	Minsk
Belarus	Investigator Site 3603	Minsk
Belarus	Investigator Site 3604	Vitebsk
Belarus	Investigator Site 3606	Vitebsk
Bosnia and Herzegovina	Investigator Site 9104	Sarajevo
Bulgaria	Investigator Site 2709	Plovdiv
Bulgaria	Investigator Site 2701	Sofia
Bulgaria	Investigator Site 2702	Sofia
Bulgaria	Investigator Site 2703	Sofia
Bulgaria	Investigator Site 2707	Sofia
Bulgaria	Investigator Site 2708	Sofia
Bulgaria	Investigator Site 2711	Sofia
Canada	Investigator Site 8102	Edmonton	Alberta
Canada	Investigator Site 8113	Greenfield Park	Quebec
Canada	Investigator Site 8101	Ottawa	Ontario
Canada	Investigator Site 8120	Victoria	British Columbia
Croatia	Investigator Site 2506	Osijek
Croatia	Investigator Site 2502	Zagreb
Croatia	Investigator Site 2508	Zagreb
Croatia	Investigator Site 2509	Zagreb
Czechia	Investigator Site 3003	Brno
Czechia	Investigator Site 3009	Brno
Czechia	Investigator Site 3010	Hradec Králové
Czechia	Investigator Site 3006	Jihlava
Czechia	Investigator Site 3002	Ostrava-Poruba
Czechia	Investigator Site 3007	Pardubice
Czechia	Investigator Site 3001	Praha 2
Czechia	Investigator Site 3008	Praha 5
Czechia	Investigator Site 3004	Teplice
Finland	Investigator Site 2212	Tampere
Finland	Investigator Site 2202	Turku
France	Investigator Site 1713	Bordeaux Cedex
France	Investigator Site 1703	Clermont Ferrand Cedex 1
France	Investigator Site 1715	Nantes Cedex 1
France	Investigator Site 1706	Nice Cedex 1
France	Investigator Site 1705	Strasbourg Cedex
Georgia	Investigator Site 3902	Tbilisi
Georgia	Investigator Site 3903	Tbilisi
Georgia	Investigator Site 3904	Tbilisi
Georgia	Investigator Site 3905	Tbilisi
Georgia	Investigator Site 3906	Tbilisi
Germany	Investigator Site 1113	Dresden
Germany	Investigator Site 1107	Erfurt
Germany	Investigator Site 1109	Leipzig
Germany	Investigator Site 1104	Mainz
Germany	Investigator Site 1102	Ulm
Greece	Investigator Site 1301	Athens
Greece	Investigator Site 1303	Athens
Greece	Investigator Site 1307	Athens
Hungary	Investigator Site 2903	Budapest
Hungary	Investigator Site 2905	Budapest
Hungary	Investigator Site 2910	Esztergom
Hungary	Investigator Site 2902	Gyor
Hungary	Investigator Site 2909	Kistarcsa
Israel	Investigator Site 4005	Ashkelon
Israel	Investigator Site 4004	Haifa
Israel	Investigator Site 4006	Jerusalem
Israel	Investigator Site 4010	Zfat
Italy	Investigator Site 1403	Cefalu
Italy	Investigator Site 1409	Genova
Italy	Investigator Site 1413	L'Aquila
Italy	Investigator Site 1405	Roma
Latvia	Investigator Site 3401	Riga
Latvia	Investigator Site 3402	Riga
Latvia	Investigator Site 3403	Riga
Lithuania	Investigator Site 3502	Kaunas
Lithuania	Investigator Site 3503	Klaipeda
Lithuania	Investigator Site 3504	Siauliai
Mexico	Investigator Site 7410	Chihuahua
Mexico	Investigator Site 7409	Monterrey
Poland	Investigator Site 3219	Bialystok
Poland	Investigator Site 3215	Bydgoszcz
Poland	Investigator Site 3208	Gdansk
Poland	Investigator Site 3203	Katowice
Poland	Investigator Site 3217	Katowice
Poland	Investigator Site 3205	Konstancin-Jeziorna
Poland	Investigator Site 3216	Ksawerow
Poland	Investigator Site 3220	Lublin
Poland	Investigator Site 3202	Poznan
Poland	Investigator Site 3207	Poznan
Poland	Investigator Site 3214	Poznan
Poland	Investigator Site 3213	Wroclaw
Portugal	Investigator Site 1602	Amadora
Portugal	Investigator Site 1605	Braga
Portugal	Investigator Site 1603	Coimbra
Portugal	Investigator Site 1604	Porto
Romania	Investigator Site 2804	Bucuresti
Romania	Investigator Site 2807	Bucuresti
Romania	Investigator Site 2811	Bucuresti
Romania	Investigator Site 2802	Timisoara
Russian Federation	Investigator Site 3821	Barnaul	Altai Krai
Russian Federation	Investigator Site 3818	Belgorod
Russian Federation	Investigator Site 3837	Bryansk
Russian Federation	Investigator Site 3836	Ekaterinburg
Russian Federation	Investigator Site 3811	Kazan
Russian Federation	Investigator Site 3822	Kemerovo
Russian Federation	Investigator Site 3814	Krasnoyarsk
Russian Federation	Investigator Site 3823	Kursk
Russian Federation	Investigator Site 3803	Moscow
Russian Federation	Investigator Site 3810	Moscow
Russian Federation	Investigator Site 3831	Moscow
Russian Federation	Investigator Site 3840	Moscow
Russian Federation	Investigator Site 3802	Nizhniy Novgorod
Russian Federation	Investigator Site 3834	Nizhny Novgorod
Russian Federation	Investigator Site 3835	Novgorod
Russian Federation	Investigator Site 3829	Novosibirsk
Russian Federation	Investigator Site 3839	Perm
Russian Federation	Investigator Site 3812	Pyatigorsk
Russian Federation	Investigator Site 3813	Saint Petersburg
Russian Federation	Investigator Site 3805	Samara
Russian Federation	Investigator Site 3825	Smolensk
Russian Federation	Investigator Site 3807	St. Petersburg
Russian Federation	Investigator Site 3808	St. Petersburg
Russian Federation	Investigator Site 3815	St. Petersburg
Russian Federation	Investigator Site 3833	St. Petersburg
Russian Federation	Investigator Site 3801	Tomsk
Russian Federation	Investigator Site 3819	Tver
Russian Federation	Investigator Site 3842	Yaroslavl
Serbia	Investigator Site 2601	Belgrade
Serbia	Investigator Site 2606	Belgrade
Serbia	Investigator Site 2607	Belgrade
Serbia	Investigator Site 2603	Kragujevac
Serbia	Investigator Site 2602	Nis
Spain	Investigator Site 1504	Barcelona
Spain	Investigator Site 1505	Barcelona
Spain	Investigator Site 1509	Barcelona
Spain	Investigator Site 1502	Madrid
Spain	Investigator Site 1501	Malaga
Spain	Investigator Site 1506	Sevilla
Sweden	Investigator Site 2103	Goteborg
Sweden	Investigator Site 2101	Stockholm
Sweden	Investigator Site 2110	Stockholm
Turkey	Investigator Site 9004	Trabzon
Ukraine	Investigator Site 3701	Chernihiv
Ukraine	Investigator Site 3714	Chernihiv
Ukraine	Investigator Site 3711	Ivano-Frankivsk
Ukraine	Investigator Site 3713	Ivano-Frankivsk
Ukraine	Investigator Site 3723	Kharkiv
Ukraine	Investigator Site 3724	Kharkiv
Ukraine	Investigator Site 3716	Kyiv
Ukraine	Investigator Site 3715	Lviv
Ukraine	Investigator Site 3721	Lviv
Ukraine	Investigator Site 3703	Odessa
Ukraine	Investigator Site 3717	Poltava
Ukraine	Investigator Site 3730	Ternopil
Ukraine	Investigator Site 3718	Vinnytsia
Ukraine	Investigator Site 3722	Zaporizhia
Ukraine	Investigator Site 3725	Zhytomyr
United Kingdom	Investigator Site 2015	Glasgow
United Kingdom	Investigator Site 2021	Lancashire
United Kingdom	Investigator Site 2003	Salford
United States	Investigator Site 8045	Carlsbad	California
United States	Investigator Site 8006	Columbus	Ohio
United States	Investigator Site 8036	Denver	Colorado
United States	Investigator Site 8015	Franklin	Tennessee
United States	Investigator Site 8013	Indianapolis	Indiana
United States	Investigator Site 8042	Orem	Utah
United States	Investigator Site 8065	Ormond Beach	Florida
United States	Investigator Site 8311	Pomona	California
United States	Investigator Site 8040	Raleigh	North Carolina
United States	Investigator Site 8018	Tampa	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Actelion

Countries where clinical trial is conducted

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Annualized Confirmed Relapse Rate	Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual,Brain Stem,Pyramidal,Cerebellar,Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS).	From randomization to end of study (Week 108)
Secondary	Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108	The FSIQ-RMS is a 20-item Patient Reported Outcomes (PRO) measure to evaluate fatigue-related symptoms and the impacts of those symptoms on the lives of people. The FSIQ-RMS symptom domain (FSIQ-RMS-S) consists of seven items assessing fatigue-related symptoms daily with a recall period of 24 hours measured on an 11-point numeric rating scale; the (normalized) symptom domain score ranges from 0 to 100 with a higher score indicating greater fatigue. This domain was completed on 7 consecutive days. A negative change from baseline indicates an improvement in fatigue symptoms.	Baseline to Week 108
Secondary	Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108	CUALs was calculated as sum of new Gadolinium-enhanced (Gd+) T1 lesions plus new or enlarging T2 lesions (without double-counting of lesions) from baseline based on the Magnetic resonance imaging (MRI) scans up to Week 108. Average number of lesions per year were reported.	Baseline to Week 108
Secondary	12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS	A 12-week CDA was defined as an increase of at least 1.5 in Expanded Disability Status Scale (EDSS) for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score greater than or equal to (>=) 5.5, which was confirmed after 12 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS).	Baseline to Week 60 and 108 Weeks
Secondary	24-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS	A 24-week CDA was defined as an increase of at least 1.5 in EDSS for participants with a baseline EDSS score of 0.0 or an increase of at least 1.0 in EDSS for participants with a baseline EDSS score of 1.0 to 5.0, or an increase of at least 0.5 in EDSS for participants with a baseline EDSS score >= 5.5, which was confirmed after 24 weeks. Baseline EDSS was defined as the last EDSS score recorded prior to randomization. The EDSS is an ordinal scale ranging from 0 (normal neurological exam) to 10 (death to MS).	Baseline to 60 Weeks and 108 Weeks

External Links

•   Multicenter, randomized, double-blind, parallel-group, active-controlled, superiority study to compare the efficacy and safety of ponesimod to teriflunomide in subjects with relapsing multiple sclerosis