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| ID | Type | Description | Link |
|---|---|---|---|
| 2012-000540-10 | EudraCT Number |
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International clinical trial to compare ponesimod and teriflunomide in relapsing multiple sclerosis
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ponesimod | Experimental | Subjects to receive 20 mg ponesimod |
|
| Teriflunomide | Active Comparator | Subjects to receive 14 mg teriflunomide |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ponesimod | Drug | film-coated tablet with 20 mg ponesimod, administered orally once daily in the morning |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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) |
| Measure | Description | Time Frame |
|---|---|---|
| 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. |
Not provided
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.
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| Name | Affiliation | Role |
|---|---|---|
| Tatiana Scherz, MD, PhD | Actelion | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Investigator Site 8045 | Carlsbad | California | 92011 | United States | ||
| Investigator Site 8311 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38301149 | Derived | Jones RR, Turkoz I, Ait-Tihyaty M, DiBernardo A, Houtchens MK, Havrdova EK. Efficacy and Safety of Ponesimod Compared with Teriflunomide in Female Patients with Relapsing Multiple Sclerosis: Findings from the Pivotal OPTIMUM Study. J Womens Health (Larchmt). 2024 Apr;33(4):480-490. doi: 10.1089/jwh.2023.0037. Epub 2024 Feb 1. | |
| 37155132 |
| Label | URL |
|---|---|
| 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 | View source |
Not provided
As planned, Placebo was not a separate arm as this was included for double dummy design study part (up to Day 14).
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| ID | Title | Description |
|---|---|---|
| FG000 | Ponesimod 20 mg | Participants were up-titrated during Days 1 to 14 from 2 to 10 mg of ponesimod once daily (one ponesimod tablet and one matching placebo capsule per day). From Day 15 to Week 108 participants received ponesimod 20 mg once daily up to Week 108 |
| FG001 | Teriflunomide 14 mg |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Dec 5, 2018 | Apr 2, 2021 |
Not provided
Not provided
Not provided
Not provided
| teriflunomide | Drug | film-coated tablet with 14 mg teriflunomide, administered orally once daily in the morning |
|
| Baseline to Week 108 |
| 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 |
| 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 |
| 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 |
| Pomona |
| California |
| 91767 |
| United States |
| Investigator Site 8036 | Denver | Colorado | 80209 | United States |
| Investigator Site 8065 | Ormond Beach | Florida | 32174 | United States |
| Investigator Site 8018 | Tampa | Florida | 33612 | United States |
| Investigator Site 8013 | Indianapolis | Indiana | 46256 | United States |
| Investigator Site 8040 | Raleigh | North Carolina | 27607 | United States |
| Investigator Site 8006 | Columbus | Ohio | 43214 | United States |
| Investigator Site 8015 | Franklin | Tennessee | 37064 | United States |
| Investigator Site 8042 | Orem | Utah | 84058 | United States |
| Investigator Site 3605 | Grodno | 230017 | Belarus |
| Investigator Site 3603 | Minsk | 220026 | Belarus |
| Investigator Site 3602 | Minsk | 220114 | Belarus |
| Investigator Site 3606 | Vitebsk | 210023 | Belarus |
| Investigator Site 3604 | Vitebsk | 210037 | Belarus |
| Investigator Site 9104 | Sarajevo | 71000 | Bosnia and Herzegovina |
| Investigator Site 2709 | Plovdiv | 4002 | Bulgaria |
| Investigator Site 2711 | Sofia | 1113 | Bulgaria |
| Investigator Site 2702 | Sofia | 1309 | Bulgaria |
| Investigator Site 2707 | Sofia | 1407 | Bulgaria |
| Investigator Site 2701 | Sofia | 1431 | Bulgaria |
| Investigator Site 2708 | Sofia | 1431 | Bulgaria |
| Investigator Site 2703 | Sofia | 1606 | Bulgaria |
| Investigator Site 8102 | Edmonton | Alberta | T6G 1Z1 | Canada |
| Investigator Site 8120 | Victoria | British Columbia | V8R 1J8 | Canada |
| Investigator Site 8101 | Ottawa | Ontario | K1H 8L6 | Canada |
| Investigator Site 8113 | Greenfield Park | Quebec | J4V 2J2 | Canada |
| Investigator Site 2506 | Osijek | 31000 | Croatia |
| Investigator Site 2502 | Zagreb | 10000 | Croatia |
| Investigator Site 2508 | Zagreb | 10000 | Croatia |
| Investigator Site 2509 | Zagreb | 10000 | Croatia |
| Investigator Site 3009 | Brno | 625 00 | Czechia |
| Investigator Site 3003 | Brno | 656 91 | Czechia |
| Investigator Site 3010 | Hradec Králové | 500 05 | Czechia |
| Investigator Site 3006 | Jihlava | 586 33 | Czechia |
| Investigator Site 3002 | Ostrava-Poruba | 708 52 | Czechia |
| Investigator Site 3007 | Pardubice | 532 03 | Czechia |
| Investigator Site 3001 | Prague | 128 08 | Czechia |
| Investigator Site 3008 | Prague | 150 06 | Czechia |
| Investigator Site 3004 | Teplice | 415 29 | Czechia |
| Investigator Site 2212 | Tampere | 33100 | Finland |
| Investigator Site 2202 | Turku | 20520 | Finland |
| Investigator Site 1713 | Bordeaux | 33076 | France |
| Investigator Site 1703 | Clermont-Ferrand | 63003 | France |
| Investigator Site 1715 | Nantes | 44093 | France |
| Investigator Site 1706 | Nice | 06002 | France |
| Investigator Site 1705 | Strasbourg | 67091 | France |
| Investigator Site 3905 | Tbilisi | 0112 | Georgia |
| Investigator Site 3904 | Tbilisi | 0160 | Georgia |
| Investigator Site 3903 | Tbilisi | 0179 | Georgia |
| Investigator Site 3906 | Tbilisi | 0179 | Georgia |
| Investigator Site 3902 | Tbilisi | 0194 | Georgia |
| Investigator Site 1113 | Dresden | 01307 | Germany |
| Investigator Site 1107 | Erfurt | 99089 | Germany |
| Investigator Site 1109 | Leipzig | 04107 | Germany |
| Investigator Site 1104 | Mainz | 55131 | Germany |
| Investigator Site 1102 | Ulm | 89081 | Germany |
| Investigator Site 1303 | Athens | 11521 | Greece |
| Investigator Site 1301 | Athens | 11525 | Greece |
| Investigator Site 1307 | Athens | 15125 | Greece |
| Investigator Site 2903 | Budapest | 1145 | Hungary |
| Investigator Site 2905 | Budapest | 1204 | Hungary |
| Investigator Site 2910 | Esztergom | 2500 | Hungary |
| Investigator Site 2902 | Győr | 9023 | Hungary |
| Investigator Site 2909 | Kistarcsa | 2143 | Hungary |
| Investigator Site 4005 | Ashkelon | 7830604 | Israel |
| Investigator Site 4004 | Haifa | 3109601 | Israel |
| Investigator Site 4006 | Jerusalem | 9112001 | Israel |
| Investigator Site 4010 | Zfat | 13100 | Israel |
| Investigator Site 1403 | Cefalù | 90015 | Italy |
| Investigator Site 1409 | Genova | 16132 | Italy |
| Investigator Site 1413 | L’Aquila | 67100 | Italy |
| Investigator Site 1405 | Roma | 00189 | Italy |
| Investigator Site 3401 | Riga | 1015 | Latvia |
| Investigator Site 3402 | Riga | LV-1002 | Latvia |
| Investigator Site 3403 | Riga | LV-1038 | Latvia |
| Investigator Site 3502 | Kaunas | 50161 | Lithuania |
| Investigator Site 3503 | KlaipÄ—da | 92288 | Lithuania |
| Investigator Site 3504 | Å iauliai | 76231 | Lithuania |
| Investigator Site 7410 | Chihuahua City | 31203 | Mexico |
| Investigator Site 7409 | Monterrey | 64710 | Mexico |
| Investigator Site 3219 | Bialystok | 15-270 | Poland |
| Investigator Site 3215 | Bydgoszcz | 85-795 | Poland |
| Investigator Site 3208 | Gdansk | 80-803 | Poland |
| Investigator Site 3217 | Katowice | 40-595 | Poland |
| Investigator Site 3203 | Katowice | 40-752 | Poland |
| Investigator Site 3205 | Konstancin-Jeziorna | 05-510 | Poland |
| Investigator Site 3216 | Ksawerów | 95-054 | Poland |
| Investigator Site 3220 | Lublin | 20-015 | Poland |
| Investigator Site 3202 | Poznan | 60-355 | Poland |
| Investigator Site 3214 | Poznan | 60-848 | Poland |
| Investigator Site 3207 | Poznan | 61-853 | Poland |
| Investigator Site 3213 | Wroclaw | 51-685 | Poland |
| Investigator Site 1602 | Amadora | 2720 276 | Portugal |
| Investigator Site 1605 | Braga | 4710-243 | Portugal |
| Investigator Site 1603 | Coimbra | 3000-075 | Portugal |
| Investigator Site 1604 | Porto | 4099-001 | Portugal |
| Investigator Site 2807 | Bucharest | 010825 | Romania |
| Investigator Site 2811 | Bucharest | 022903 | Romania |
| Investigator Site 2804 | Bucharest | 050098 | Romania |
| Investigator Site 2802 | Timișoara | 300723 | Romania |
| Investigator Site 3821 | Barnaul | Altayskiy Kray | 656024 | Russia |
| Investigator Site 3818 | Belgorod | 308007 | Russia |
| Investigator Site 3837 | Bryansk | 241033 | Russia |
| Investigator Site 3811 | Kazan' | 420029 | Russia |
| Investigator Site 3822 | Kemerovo | 650066 | Russia |
| Investigator Site 3814 | Krasnoyarsk | 660037 | Russia |
| Investigator Site 3823 | Kursk | 305007 | Russia |
| Investigator Site 3831 | Moscow | 119049 | Russia |
| Investigator Site 3803 | Moscow | 127015 | Russia |
| Investigator Site 3840 | Moscow | 127015 | Russia |
| Investigator Site 3810 | Moscow | 129128 | Russia |
| Investigator Site 3834 | Nizhny Novgorod | 603076 | Russia |
| Investigator Site 3802 | Nizhny Novgorod | 603155 | Russia |
| Investigator Site 3829 | Novosibirsk | 630007 | Russia |
| Investigator Site 3839 | Perm | 614990 | Russia |
| Investigator Site 3812 | Pyatigorsk | 357538 | Russia |
| Investigator Site 3808 | Saint Petersburg | 194354 | Russia |
| Investigator Site 3833 | Saint Petersburg | 197022 | Russia |
| Investigator Site 3813 | Saint Petersburg | 197110 | Russia |
| Investigator Site 3807 | Saint Petersburg | 197376 | Russia |
| Investigator Site 3815 | Saint Petersburg | 197706 | Russia |
| Investigator Site 3805 | Samara | 443095 | Russia |
| Investigator Site 3825 | Smolensk | 214019 | Russia |
| Investigator Site 3801 | Tomsk | 634050 | Russia |
| Investigator Site 3819 | Tver' | 170026 | Russia |
| Investigator Site 3835 | Veliky Novgorod | 173008 | Russia |
| Investigator Site 3842 | Yaroslavl | 150030 | Russia |
| Investigator Site 3836 | Yekaterinburg | 620102 | Russia |
| Investigator Site 2601 | Belgrade | 11000 | Serbia |
| Investigator Site 2606 | Belgrade | 11000 | Serbia |
| Investigator Site 2607 | Belgrade | 11080 | Serbia |
| Investigator Site 2603 | Kragujevac | 34000 | Serbia |
| Investigator Site 2602 | Niš | 18000 | Serbia |
| Investigator Site 1509 | Barcelona | 08003 | Spain |
| Investigator Site 1505 | Barcelona | 08035 | Spain |
| Investigator Site 1504 | Barcelona | 08036 | Spain |
| Investigator Site 1502 | Madrid | 28006 | Spain |
| Investigator Site 1501 | Málaga | 29010 | Spain |
| Investigator Site 1506 | Seville | 41009 | Spain |
| Investigator Site 2103 | Gothenburg | 413 45 | Sweden |
| Investigator Site 2110 | Stockholm | 141 86 | Sweden |
| Investigator Site 2101 | Stockholm | 171 76 | Sweden |
| Investigator Site 9004 | Trabzon | 61080 | Turkey (Türkiye) |
| Investigator Site 3714 | Chernihiv | 14001 | Ukraine |
| Investigator Site 3701 | Chernihiv | 14029 | Ukraine |
| Investigator Site 3713 | Ivano-Frankivsk | 76008 | Ukraine |
| Investigator Site 3711 | Ivano-Frankivsk | 76018 | Ukraine |
| Investigator Site 3723 | Kharkiv | 61103 | Ukraine |
| Investigator Site 3724 | Kharkiv | 61176 | Ukraine |
| Investigator Site 3716 | Kyiv | 03115 | Ukraine |
| Investigator Site 3715 | Lviv | 79000 | Ukraine |
| Investigator Site 3721 | Lviv | 79010 | Ukraine |
| Investigator Site 3703 | Odesa | 65009 | Ukraine |
| Investigator Site 3717 | Poltava | 36011 | Ukraine |
| Investigator Site 3730 | Ternopil | 46027 | Ukraine |
| Investigator Site 3718 | Vinnytsia | 21005 | Ukraine |
| Investigator Site 3722 | Zaporizhia | 69000 | Ukraine |
| Investigator Site 3725 | Zhytomyr | 10008 | Ukraine |
| Investigator Site 2015 | Glasgow | G51 4TF | United Kingdom |
| Investigator Site 2021 | Lancashire | PR2 9HT | United Kingdom |
| Investigator Site 2003 | Salford | M6 8HD | United Kingdom |
| Jiang T, Ziemssen T, Wray S, Shen C, Soderbarg K, Lewin JB, Bozin I, Freedman MS. Matching-Adjusted Indirect Comparisons of Diroximel Fumarate, Ponesimod, and Teriflunomide for Relapsing Multiple Sclerosis. CNS Drugs. 2023 May;37(5):441-452. doi: 10.1007/s40263-023-01002-x. Epub 2023 May 8. |
| 36550636 | Derived | Fox RJ, Tervonen T, Phillips-Beyer A, Sidorenko T, Boyanova N, Brooks A, Hennessy B, Jamieson C, Levitan B. The relevance of fatigue to relapse rate in multiple sclerosis: Applying patient preference data to the OPTIMUM trial. Mult Scler. 2023 Mar;29(3):427-435. doi: 10.1177/13524585221140270. Epub 2022 Dec 22. |
| 36047474 | Derived | Valenzuela B, Olsson Gisleskog P, Poggesi I, Sidorenko T, Burcklen M, Kracker H, Perez-Ruixo JJ. An exposure-response analysis of ponesimod clinical efficacy in a randomized phase III study in patients with relapsing multiple sclerosis. CPT Pharmacometrics Syst Pharmacol. 2022 Oct;11(10):1294-1304. doi: 10.1002/psp4.12778. Epub 2022 Sep 1. |
| 33779698 | Derived | Kappos L, Fox RJ, Burcklen M, Freedman MS, Havrdova EK, Hennessy B, Hohlfeld R, Lublin F, Montalban X, Pozzilli C, Scherz T, D'Ambrosio D, Linscheid P, Vaclavkova A, Pirozek-Lawniczek M, Kracker H, Sprenger T. Ponesimod Compared With Teriflunomide in Patients With Relapsing Multiple Sclerosis in the Active-Comparator Phase 3 OPTIMUM Study: A Randomized Clinical Trial. JAMA Neurol. 2021 May 1;78(5):558-567. doi: 10.1001/jamaneurol.2021.0405. |
Participants received teriflunomide 14 mg capsule once daily from Day 1 up to Week 108. During Days 1 to 14 (mock uptitration period), participants received in addition one tablet of matching placebo. |
| Treated |
|
| COMPLETED |
|
| NOT COMPLETED |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Ponesimod 20 mg | Participants were up-titrated during Days 1 to 14 from 2 to 10 mg of ponesimod once daily (one ponesimod tablet and one matching placebo capsule per day). From Day 15 to Week 108 participants received ponesimod 20 mg once daily up to Week 108 |
| BG001 | Teriflunomide 14 mg | Participants received teriflunomide 14 mg capsule once daily from Day 1 up to Week 108. During Days 1 to 14 (mock uptitration period), participants received in addition one tablet of matching placebo. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||
| Region of Enrollment | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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). | Full analysis set (FAS) included all participants randomized in the study. | Posted | Mean | 99% Confidence Interval | relapses per year | 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. | FAS included all participants randomized in the study. Here 'N' (number of participants analyzed) included all participants who were evaluable for this outcome measure with available baseline and at least one post-baseline assessment. | Posted | Least Squares Mean | 95% Confidence Interval | score on scale | 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. | FAS included all participants randomized in the study. Here 'N' (number of participants analyzed) signifies number of participants evaluable for this outcome measure. | Posted | Mean | 95% Confidence Interval | lesions per year | 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). | FAS included all participants randomized in this study. | Posted | Number | 95% Confidence Interval | Percentage of Participants | 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). | FAS included all participants randomized in this study. | Posted | Number | 95% Confidence Interval | Percentage of Participants | Baseline to 60 Weeks and 108 Weeks |
|
Up to 111 Weeks (From treatment start [Day 1] to end of treatment [Week 108] plus 15 days)
Safety analysis set included all participants who received at least one dose of study treatment.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Ponesimod 20 mg | Participants were up-titrated during Days 1 to 14 from 2 to 10 mg of ponesimod once daily (one ponesimod tablet and one matching placebo capsule per day). From Day 15 to Week 108 participants received ponesimod 20 mg once daily up to Week 108 | 0 | 565 | 49 | 565 | 434 | 565 |
| EG001 | Teriflunomide 14 mg | Participants received teriflunomide 14 mg capsule once daily from Day 1 up to Week 108. During Days 1 to 14 (mock uptitration period), participants received in addition one tablet of matching placebo. | 2 | 566 | 46 | 566 | 422 | 566 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Lymphadenitis | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Atrial Fibrillation | Cardiac disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Coronary Artery Insufficiency | Cardiac disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Bowel Movement Irregularity | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Duodenal Ulcer Haemorrhage | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Duodenitis | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Gastritis | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Haemorrhoidal Haemorrhage | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Intestinal Haemorrhage | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pancreatitis Acute | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Biliary Colic | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Cholecystitis Acute | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Cholecystitis Chronic | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Cholelithiasis | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Drug-Induced Liver Injury | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hepatitis | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hepatitis Toxic | Hepatobiliary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Abdominal Infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Herpes Zoster | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Lymph Node Abscess | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Meningitis Enteroviral | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pilonidal Cyst | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Salpingitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Vestibular Neuronitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Concussion | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Fall | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Femur Fracture | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Fibula Fracture | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Jaw Fracture | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Ligament Injury | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Meniscus Injury | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Multiple Injuries | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Post Procedural Haematoma | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Soft Tissue Injury | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Toxicity to Various Agents | Injury, poisoning and procedural complications | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hepatic Enzyme Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Transaminases Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Intervertebral Disc Protrusion | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Myofascial Pain Syndrome | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Rheumatoid Arthritis | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Spinal Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Synovitis | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Basal Cell Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Eyelid Haemangioma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Invasive Ductal Breast Carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Malignant Melanoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pituitary Tumour Benign | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Squamous Cell Carcinoma of the Cervix | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Uterine Leiomyoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Clonic Convulsion | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Epilepsy | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Ischaemic Stroke | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Loss of Consciousness | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Lumbar Radiculopathy | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Multiple Sclerosis | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Multiple Sclerosis Relapse | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Partial Seizures with Secondary Generalisation | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Restless Legs Syndrome | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Trigeminal Neuralgia | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Conversion Disorder | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Panic Attack | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Nephrolithiasis | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Renal Colic | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Tubulointerstitial Nephritis | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Ureterolithiasis | Renal and urinary disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Breast Cyst | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Endometrial Hyperplasia | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Endometriosis | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Menorrhagia | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Metrorrhagia | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Ovarian Cyst | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pelvic Adhesions | Reproductive system and breast disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Bronchospasm | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hyperventilation | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Abortion Induced | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Haemorrhoid Operation | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hysterectomy | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Ligament Operation | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Uterine Dilation and Curettage | Surgical and medical procedures | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Deep Vein Thrombosis | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hypertensive Crisis | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Raynaud's Phenomenon | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Thrombophlebitis Superficial | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Neutropenia | Blood and lymphatic system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Abdominal Pain | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Abdominal Pain Upper | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Constipation | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Dyspepsia | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Asthenia | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Fatigue | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Bronchitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Gastroenteritis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Nasopharyngitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Oral Herpes | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pharyngitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Respiratory Tract Infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Respiratory Tract Infection Viral | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Rhinitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Tonsillitis | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Upper Respiratory Tract Infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Urinary Tract Infection | Infections and infestations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Alanine Aminotransferase Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Aspartate Aminotransferase Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| C-Reactive Protein Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hepatic Enzyme Increased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Weight Decreased | Investigations | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Back Pain | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Pain in Extremity | Musculoskeletal and connective tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Dizziness | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hypoaesthesia | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Paraesthesia | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Somnolence | Nervous system disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Anxiety | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Rash | Skin and subcutaneous tissue disorders | MedDRA Version 19.1 | Non-systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA Version 19.1 | Non-systematic Assessment |
|
Low probability of this study to provide robust evaluation of ponesimod effect on disability accumulation compared to active comparator; study was not powered for this secondary endpoint. Impact of accelerated elimination procedure during safety follow-up: Accelerated elimination procedure for teriflunomide with cholestyramine/activated charcoal was frequently associated with benign, transient elevation in liver enzymes. Confounding effect of this procedure on assessing liver test was included.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Senior Director Clinical Leader | Actelion Pharmaceuticals Ltd (a Janssen Pharmaceutical Company of Johnson & Johnson) | 844-434-4210 | ClinicalTrialDisclosure@its.jnj.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jun 20, 2019 | Apr 2, 2021 | SAP_001.pdf |
| ID | Term |
|---|---|
| D009103 | Multiple Sclerosis |
| ID | Term |
|---|---|
| D020278 | Demyelinating Autoimmune Diseases, CNS |
| D020274 | Autoimmune Diseases of the Nervous System |
| D009422 | Nervous System Diseases |
| D003711 | Demyelinating Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C550169 | ponesimod |
| C527525 | teriflunomide |
Not provided
Not provided
Not provided
| Male |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
| BULGARIA |
|
| CANADA |
|
| CROATIA |
|
| CZECH REPUBLIC |
|
| FINLAND |
|
| FRANCE |
|
| GEORGIA |
|
| GERMANY |
|
| GREECE |
|
| HUNGARY |
|
| ISRAEL |
|
| ITALY |
|
| LATVIA |
|
| LITHUANIA |
|
| MEXICO |
|
| POLAND |
|
| PORTUGAL |
|
| ROMANIA |
|
| RUSSIAN FEDERATION |
|
| SPAIN |
|
| SWEDEN |
|
| TURKEY |
|
| UKRAINE |
|
| UNITED KINGDOM |
|
| UNITED STATES |
|
| Serbia |
|
| Bosnia |
|
|
|
|
| Participants |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
| Units | Counts |
|---|
| Participants |
|
|
|