An Efficacy Study of Teriflunomide in Patients With Relapsing Multiple Sclerosis

Multiple Sclerosis Clinical Trial

— TOWER  

Official title:

A Multi-center Double-blind Parallel-group Placebo-controlled Study of the Efficacy and Safety of Teriflunomide in Patients With Relapsing Multiple Sclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00751881
• Other study ID #: EFC10531
• Secondary ID: 2007-004452-36
• Status: Completed
• Phase: Phase 3
• First received: May 7, 2008
• Last updated: August 26, 2015
• Start date: August 2008
• Est. completion date: August 2015

Study information

• Verified date: August 2015
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The primary objective of the study is to assess the effect of two doses of Teriflunomide, in comparison to placebo, on the frequency of multiple sclerosis (MS) relapses in patients with relapsing MS.

Key secondary objective is to assess the effect of the two doses of teriflunomide, in comparison to placebo, on disability progression.

Other secondary objectives are:

• To assess the effect of the two doses of teriflunomide in comparison to placebo on:

• Fatigue;

• Health-related quality of life, a measure of the impact of the patient's health on his or her overall well being.

• To evaluate the safety and tolerability of teriflunomide.

Description:

The study consists in:

• A core treatment period: Teriflunomide 7 mg or Teriflunomide 14 mg or placebo is administered in double-blind fashion until a fixed common end date which is approximately 48 weeks after randomization of the last participant.

• An extension treatment period: the highest dose of teriflunomide is administered in open-label fashion to participants who successfully complete the core treatment period and wish to continue.

The overall treatment period is followed by a 4-week elimination follow-up period.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1169
• Est. completion date: August 2015
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Relapsing multiple sclerosis,

• Two relapses in prior 2 years or one relapse in prior year.

Exclusion Criteria:

• Clinically relevant cardiovascular, hepatic, neurological, endocrine or other major systemic disease,

• Significantly impaired bone marrow function or, significant anemia, leukopenia or thrombocytopenia,

• Pregnant or nursing woman,

• Alcohol or drug abuse,

• Prior or concomitant use of cladribine, mitoxantrone, or other immunosuppressant agents such as azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate,

• Human immunodeficiency virus (HIV) positive,

• Any known condition or circumstance that would prevent, in the investigator's opinion, compliance or completion of the study.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Placebo (for teriflunomide)
Film-coated tablet Oral administration
• Teriflunomide
Film-coated tablet Oral administration

Locations

Country	Name	City	State
Australia	Sanofi-Aventis Investigational Site Number 036005	Bedford Park
Australia	Sanofi-Aventis Investigational Site Number 036006	Chatswood
Australia	Sanofi-Aventis Investigational Site Number 036003	Fitzroy
Australia	Sanofi-Aventis Investigational Site Number 036004	Geelong
Australia	Sanofi-Aventis Investigational Site Number 036008	Heidelberg
Australia	Sanofi-Aventis Investigational Site Number 036002	New Lambton
Australia	Sanofi-Aventis Investigational Site Number 036001	Sydney
Austria	Sanofi-Aventis Investigational Site Number 040001	Wien
Belarus	Sanofi-Aventis Investigational Site Number 112105	Grodno
Belarus	Sanofi-Aventis Investigational Site Number 112101	Minsk
Belarus	Sanofi-Aventis Investigational Site Number 112102	Minsk
Belarus	Sanofi-Aventis Investigational Site Number 112104	Minsk
Belarus	Sanofi-Aventis Investigational Site Number 112103	Vitebsk
Belgium	Sanofi-Aventis Investigational Site Number 056004	Brugge
Belgium	Sanofi-Aventis Investigational Site Number 056002	Leuven
Belgium	Sanofi-Aventis Investigational Site Number 056001	Melsbroek
Belgium	Sanofi-Aventis Investigational Site Number 056003	Sijsele-Damme
Canada	Sanofi-Aventis Investigational Site Number 124004	Gatineau
Canada	Sanofi-Aventis Investigational Site Number 124002	Kingston
Canada	Sanofi-Aventis Investigational Site Number 124007	Montreal
Canada	Sanofi-Aventis Investigational Site Number 124008	Ottawa
Canada	Sanofi-Aventis Investigational Site Number 124001	Quebec
Canada	Sanofi-Aventis Investigational Site Number 124003	Regina
Canada	Sanofi-Aventis Investigational Site Number 124006	Saint John
Chile	Sanofi-Aventis Investigational Site Number 152006	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152007	Santiago
Chile	Sanofi-Aventis Investigational Site Number 152002	Viña Del Mar
China	Sanofi-Aventis Investigational Site Number 156023	Baotou
China	Sanofi-Aventis Investigational Site Number 156001	Beijing
China	Sanofi-Aventis Investigational Site Number 156005	Beijing
China	Sanofi-Aventis Investigational Site Number 156006	Beijing
China	Sanofi-Aventis Investigational Site Number 156008	Beijing
China	Sanofi-Aventis Investigational Site Number 156010	Beijing
China	Sanofi-Aventis Investigational Site Number 156024	Beijing
China	Sanofi-Aventis Investigational Site Number 156030	Beijing
China	Sanofi-Aventis Investigational Site Number 156031	Beijing
China	Sanofi-Aventis Investigational Site Number 156032	Beijing
China	Sanofi-Aventis Investigational Site Number 156007	Changchun
China	Sanofi-Aventis Investigational Site Number 156002	Chengdu
China	Sanofi-Aventis Investigational Site Number 156012	Guangzhou
China	Sanofi-Aventis Investigational Site Number 156025	Guangzhou
China	Sanofi-Aventis Investigational Site Number 156027	Haikou
China	Sanofi-Aventis Investigational Site Number 156021	Hangzhou
China	Sanofi-Aventis Investigational Site Number 156033	Jinan
China	Sanofi-Aventis Investigational Site Number 156011	Nanjing
China	Sanofi-Aventis Investigational Site Number 156034	Nanjing
China	Sanofi-Aventis Investigational Site Number 156019	Qingdao
China	Sanofi-Aventis Investigational Site Number 156016	Shanghai
China	Sanofi-Aventis Investigational Site Number 156029	Shanghai
China	Sanofi-Aventis Investigational Site Number 156009	Shenyang
China	Sanofi-Aventis Investigational Site Number 156022	Shijiazhuang
China	Sanofi-Aventis Investigational Site Number 156018	Suzhou
China	Sanofi-Aventis Investigational Site Number 156028	Taiyuan
China	Sanofi-Aventis Investigational Site Number 156003	Tianjin
China	Sanofi-Aventis Investigational Site Number 156035	Tianjin
China	Sanofi-Aventis Investigational Site Number 156017	Wenzhou
China	Sanofi-Aventis Investigational Site Number 156004	Wuhan
China	Sanofi-Aventis Investigational Site Number 156014	Xi'An
China	Sanofi-Aventis Investigational Site Number 156015	Xi'An
Czech Republic	Sanofi-Aventis Investigational Site Number 203001	Brno
Czech Republic	Sanofi-Aventis Investigational Site Number 203002	Ostrava - Poruba
Czech Republic	Sanofi-Aventis Investigational Site Number 203004	Teplice
Estonia	Sanofi-Aventis Investigational Site Number 233002	Tallinn
Estonia	Sanofi-Aventis Investigational Site Number 233001	Tartu
France	Sanofi-Aventis Investigational Site Number 250005	Besancon
France	Sanofi-Aventis Investigational Site Number 250008	Dijon Cedex
France	Sanofi-Aventis Investigational Site Number 250001	Lyon Cedex 03
France	Sanofi-Aventis Investigational Site Number 250007	Nantes Cedex 01
France	Sanofi-Aventis Investigational Site Number 250006	Nice Cedex
France	Sanofi-Aventis Investigational Site Number 250002	Nimes
France	Sanofi-Aventis Investigational Site Number 250003	Poissy
Germany	Sanofi-Aventis Investigational Site Number 276010	Bamberg
Germany	Sanofi-Aventis Investigational Site Number 276003	Bayreuth
Germany	Sanofi-Aventis Investigational Site Number 276005	Berlin
Germany	Sanofi-Aventis Investigational Site Number 276001	Erlangen
Germany	Sanofi-Aventis Investigational Site Number 276006	Gießen
Germany	Sanofi-Aventis Investigational Site Number 276004	Hannover
Germany	Sanofi-Aventis Investigational Site Number 276007	Leipzig
Germany	Sanofi-Aventis Investigational Site Number 276009	Magdeburg
Germany	Sanofi-Aventis Investigational Site Number 276002	Wiesbaden
Greece	Sanofi-Aventis Investigational Site Number 300001	Athens
Greece	Sanofi-Aventis Investigational Site Number 300006	Thessaloniki
Mexico	Sanofi-Aventis Investigational Site Number 484003	México
Mexico	Sanofi-Aventis Investigational Site Number 484005	Monterrey
Netherlands	Sanofi-Aventis Investigational Site Number 528003	'S Hertogenbosch
Netherlands	Sanofi-Aventis Investigational Site Number 528001	Breda
Netherlands	Sanofi-Aventis Investigational Site Number 528002	Groesbeek
Netherlands	Sanofi-Aventis Investigational Site Number 528004	Nieuwegein
Netherlands	Sanofi-Aventis Investigational Site Number 528006	Sittard-Geleen
Philippines	Sanofi-Aventis Investigational Site Number 608004	Cebu City
Philippines	Sanofi-Aventis Investigational Site Number 608002	Makati City
Philippines	Sanofi-Aventis Investigational Site Number 608001	Manila
Philippines	Sanofi-Aventis Investigational Site Number 608003	Quezon City
Poland	Sanofi-Aventis Investigational Site Number 616002	Gdansk
Poland	Sanofi-Aventis Investigational Site Number 616005	Lodz
Poland	Sanofi-Aventis Investigational Site Number 616001	Lublin
Poland	Sanofi-Aventis Investigational Site Number 616004	Szczecin
Poland	Sanofi-Aventis Investigational Site Number 616003	Warszawa 44
Romania	Sanofi-Aventis Investigational Site Number 642006	Bacau
Romania	Sanofi-Aventis Investigational Site Number 642005	Brasov
Romania	Sanofi-Aventis Investigational Site Number 642001	Bucuresti
Romania	Sanofi-Aventis Investigational Site Number 642007	Oradea
Slovakia	Sanofi-Aventis Investigational Site Number 703003	Bratislava 2
Slovakia	Sanofi-Aventis Investigational Site Number 703005	Bratislava 2
Slovakia	Sanofi-Aventis Investigational Site Number 703001	Martin
Slovakia	Sanofi-Aventis Investigational Site Number 703006	Presov
Spain	Sanofi-Aventis Investigational Site Number 724001	Barcelona
Spain	Sanofi-Aventis Investigational Site Number 724007	Getafe
Spain	Sanofi-Aventis Investigational Site Number 724002	Girona
Spain	Sanofi-Aventis Investigational Site Number 724004	Madrid
Spain	Sanofi-Aventis Investigational Site Number 724003	Sevilla
Sweden	Sanofi-Aventis Investigational Site Number 752001	Stockholm
Sweden	Sanofi-Aventis Investigational Site Number 752002	Stockholm
Sweden	Sanofi-Aventis Investigational Site Number 752003	Stockholm
Thailand	Sanofi-Aventis Investigational Site Number 764001	Bangkok
Thailand	Sanofi-Aventis Investigational Site Number 764002	Bangkok-Noi
Tunisia	Sanofi-Aventis Investigational Site Number 788003	Manouba
Tunisia	Sanofi-Aventis Investigational Site Number 788004	Sfax
Tunisia	Sanofi-Aventis Investigational Site Number 788001	Tunis
Tunisia	Sanofi-Aventis Investigational Site Number 788002	Tunis
Turkey	Sanofi-Aventis Investigational Site Number 792011	Edirne
Turkey	Sanofi-Aventis Investigational Site Number 792001	Istanbul
Turkey	Sanofi-Aventis Investigational Site Number 792007	Istanbul
Turkey	Sanofi-Aventis Investigational Site Number 792009	Istanbul
Turkey	Sanofi-Aventis Investigational Site Number 792010	Istanbul
Turkey	Sanofi-Aventis Investigational Site Number 792012	Izmir
Turkey	Sanofi-Aventis Investigational Site Number 792002	Kocaeli
Turkey	Sanofi-Aventis Investigational Site Number 792003	Manisa
Turkey	Sanofi-Aventis Investigational Site Number 792005	Samsun
Turkey	Sanofi-Aventis Investigational Site Number 792004	Trabzon
Ukraine	Sanofi-Aventis Investigational Site Number 804101	Chernihiv
Ukraine	Sanofi-Aventis Investigational Site Number 804103	Dnipropetrovsk
Ukraine	Sanofi-Aventis Investigational Site Number 804107	Donetsk
Ukraine	Sanofi-Aventis Investigational Site Number 804117	Donetsk
Ukraine	Sanofi-Aventis Investigational Site Number 804119	Ivano-Frankovsk
Ukraine	Sanofi-Aventis Investigational Site Number 804102	Kharkiv
Ukraine	Sanofi-Aventis Investigational Site Number 804109	Kharkov
Ukraine	Sanofi-Aventis Investigational Site Number 804108	Kiev
Ukraine	Sanofi-Aventis Investigational Site Number 804115	Kiev
Ukraine	Sanofi-Aventis Investigational Site Number 804116	Kiev
Ukraine	Sanofi-Aventis Investigational Site Number 804111	Lutsk
Ukraine	Sanofi-Aventis Investigational Site Number 804124	Lutsk
Ukraine	Sanofi-Aventis Investigational Site Number 804114	Lviv
Ukraine	Sanofi-Aventis Investigational Site Number 804121	Lviv
Ukraine	Sanofi-Aventis Investigational Site Number 804120	Poltava
Ukraine	Sanofi-Aventis Investigational Site Number 804105	Vinnytsya
Ukraine	Sanofi-Aventis Investigational Site Number 804118	Zaporizhya
Ukraine	Sanofi-Aventis Investigational Site Number 804104	Zaporizhzhia
Ukraine	Sanofi-Aventis Investigational Site Number 804122	Zaporozhye
United Kingdom	Sanofi-Aventis Investigational Site Number 826002	Edinburgh
United Kingdom	Sanofi-Aventis Investigational Site Number 826004	Haywards Heath
United Kingdom	Sanofi-Aventis Investigational Site Number 826001	Irvine
United Kingdom	Sanofi-Aventis Investigational Site Number 826003	Leeds
United Kingdom	Sanofi-Aventis Investigational Site Number 826005	Salford
United States	Sanofi-Aventis Investigational Site Number 840006	Bennington	Vermont
United States	Sanofi-Aventis Investigational Site Number 840074	Bismarck	North Dakota
United States	Sanofi-Aventis Investigational Site Number 840020	Charleston	West Virginia
United States	Sanofi-Aventis Investigational Site Number 840029	Charlotte	North Carolina
United States	Sanofi-Aventis Investigational Site Number 840026	Cincinnati	Ohio
United States	Sanofi-Aventis Investigational Site Number 840069	Clinton Township	Michigan
United States	Sanofi-Aventis Investigational Site Number 840071	Cordova	Tennessee
United States	Sanofi-Aventis Investigational Site Number 840078	Dayton	Ohio
United States	Sanofi-Aventis Investigational Site Number 840016	Des Moines	Iowa
United States	Sanofi-Aventis Investigational Site Number 840063	Elk Grove Village	Illinois
United States	Sanofi-Aventis Investigational Site Number 840011	Fairfield	Connecticut
United States	Sanofi-Aventis Investigational Site Number 840064	Flossmoor	Illinois
United States	Sanofi-Aventis Investigational Site Number 840090	Fort Collins	Colorado
United States	Sanofi-Aventis Investigational Site Number 840039	Ft Wayne	Indiana
United States	Sanofi-Aventis Investigational Site Number 840075	Grand Rapids	Michigan
United States	Sanofi-Aventis Investigational Site Number 840068	Greenville	South Carolina
United States	Sanofi-Aventis Investigational Site Number 840012	Indianapolis	Indiana
United States	Sanofi-Aventis Investigational Site Number 840008	Loma Linda	California
United States	Sanofi-Aventis Investigational Site Number 840013	Maitland	Florida
United States	Sanofi-Aventis Investigational Site Number 840076	Minneapolis	Minnesota
United States	Sanofi-Aventis Investigational Site Number 840034	Modesto	California
United States	Sanofi-Aventis Investigational Site Number 840036	Nashville	Tennessee
United States	Sanofi-Aventis Investigational Site Number 840083	Ocala	Florida
United States	Sanofi-Aventis Investigational Site Number 840086	Ormond Beach	Florida
United States	Sanofi-Aventis Investigational Site Number 840022	Philadelphia	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840073	Philadelphia	Pennsylvania
United States	Sanofi-Aventis Investigational Site Number 840041	Phoenix	Arizona
United States	Sanofi-Aventis Investigational Site Number 840024	Portland	Oregon
United States	Sanofi-Aventis Investigational Site Number 840007	San Antonio	Texas
United States	Sanofi-Aventis Investigational Site Number 840025	Sarasota	Florida
United States	Sanofi-Aventis Investigational Site Number 840089	Seattle	Washington
United States	Sanofi-Aventis Investigational Site Number 840088	St. Louis	Missouri
United States	Sanofi-Aventis Investigational Site Number 840015	St. Petersburg	Florida
United States	Sanofi-Aventis Investigational Site Number 840033	Sunrise	Florida
United States	Sanofi-Aventis Investigational Site Number 840060	Syracuse	New York
United States	Sanofi-Aventis Investigational Site Number 840061	Traverse City	Michigan
United States	Sanofi-Aventis Investigational Site Number 840084	Tucson	Arizona
United States	Sanofi-Aventis Investigational Site Number 840066	Tulsa	Oklahoma
United States	Sanofi-Aventis Investigational Site Number 840079	Tupelo	Mississippi

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Austria,  Belarus,  Belgium,  Canada,  Chile,  China,  Czech Republic,  Estonia,  France,  Germany,  Greece,  Mexico,  Netherlands,  Philippines,  Poland,  Romania,  Slovakia,  Spain,  Sweden,  Thailand,  Tunisia,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities (PCSA)	PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.; Hepatic parameters thresholds were defined as follows: Alanine Aminotransferase (ALT) >3, 5, 10 or 20 upper limit of normal(ULN); Aspartate aminotransferase (AST) >3, 5, 10 or 20 ULN; Alkaline Phosphatase >1.5 ULN; Total Bilirubin (TB) >1.5 or 2 ULN; ALT >3 ULN and TB >2 ULN.	From first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first	Yes
Primary	Annualized Relapse Rate (ARR): Poisson Regression Estimate	ARR is obtained from the total number of confirmed relapses that occurred during the treatment period divided by the sum of treatment durations.; Each episode of relapse - appearance, or worsening of a clinical symptom that was stable for at least 30 days, that persisted for a minimum of 24 hours in the absence of fever - was to be confirmed by an increase in Expanded Disability Status Scale (EDSS) score or Functional System scores.; To account for the different treatment durations among participants, a Poisson regression model with robust error variance was used (total number of confirmed relapses as response variable; log-transformed treatment duration as "offset" variable; treatment group, region of enrollment and baseline EDSS stratum as covariates).	Core treatment period between 48 - 152 weeks depending on time of enrollment	No
Secondary	Time to Disability Progression	Probability of disability progression at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to disability progression defined as the time from randomization to first 12-week sustained disability progression [i.e. increase from baseline of at least 1 point in EDSS score (at least 0.5 point for participants with baseline EDSS score >5.5) that persisted for at least 12 weeks].; Participants free of disability progression (no disability progression observed on treatment) were censored at the date of the last on-treatment EDSS evaluation.; Kaplan-Meier method consists in computing probabilities of non occurrence of event at any observed time of event and multiplying successive probabilities for time =t by any earlier computed probabilities to estimate the probability of being event-free for the amount of time t. Probability of event at time t is 1 minus the probability of being event-free for the amount of time t.	Core treatment period between 48 - 152 weeks depending on time of enrollment	No
Secondary	Time Without Relapse	Probability of no relapse at 24, 48, 108 and 132 weeks was estimated using Kaplan-Meier method on the time to relapse defined as the time from randomization to first EDSS confirmed relapse.; Participants free of confirmed relapse (no EDSS confirmed relapse observed on treatment) were censored at the date of the last study drug intake.	Core treatment period between 48 - 152 weeks depending on time of enrollment	No
Secondary	Change From Baseline to Week 48 in EDSS Total Score	EDSS is an ordinal scale in half-point increments that qualifies disability in patients with MS. It consists of 8 ordinal rating scales assessing 7 functional systems (visual, brainstem, pyramidal, cerebellar, sensory, bowel/bladder and cerebral) as well as ambulation.; EDSS total score ranges from 0 (normal neurological examination) to 10 (death due to MS).; Baseline adjusted least-squares means at Week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on EDSS score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.	Baseline (before randomization), Week 12, Week 24, Week 36 and Week 48	No
Secondary	Change From Baseline to Week 48 in Fatigue Impact Scale (FIS) Total Score	FIS is a subject-reported scale that qualifies the impact of fatigue on daily life in patients with MS. It consists of 40 statements that measure fatigue in 3 areas; physical, cognitive, and social.; FIS total score ranges from 0 (no problem) to 160 (extreme problem).; Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures (MMRM) on FIS total score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.	Baseline (before randomization), Week 12, Week 24 and Week 48	No
Secondary	Change From Baseline to Last Visit in Fatigue Impact Scale (FIS) Total Score	Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for FIS total score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).	Baseline (before randomization) and up to Week 152	No
Secondary	Change From Baseline to Week 48 in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores	SF-36 scale is a generic, self-administered, health-related quality-of-life (QOL) instrument. It is constructed such that the 36 questions represent 8 of the most important health concepts: physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health.; Two summary scores are obtained: the physical health component summary score,; the mental health component summary score.; Both scores range from 0 to 100 and a high score indicates a more favorable health state.; Baseline adjusted least-squares means at week 48 were estimated using a Mixed-effect model with repeated measures [MMRM] on each summary score data (treatment group, region of enrollment, baseline EDSS stratum, visit, treatment-by-visit interaction, baseline value, and baseline-by-visit interaction as factors). All the timepoints from randomization up to Week 48 were included in the model.	Baseline (before randomization), Week 12, Week 24 and Week 48	No
Secondary	Change From Baseline to Last Visit in Short Form Generic Health Survey - 36 Items (SF-36) Summary Scores	Baseline adjusted least-squares means at last visit were estimated using an analysis of covariance (ANCOVA) model on collected data for each summary score (treatment group, region of enrollment, baseline EDSS stratum, visit number for the last visit and baseline value as factors).	Baseline (before randomization) and up to Week 152	No
Secondary	Overview of Adverse Events	Adverse Events (AE) are any unfavorable and unintended sign, symptom, syndrome, or illness observed by the investigator or reported by the participant during the study.	From first study drug intake up to 112 days after last intake in the core treatment period or up to first intake in the extension treatment period, whichever occurred first	Yes