The Efficacy, Safety, and Tolerability of Laquinimod in Participants With Relapsing Remitting Multiple Sclerosis (RRMS)

Multiple Sclerosis Clinical Trial

— CONCERTO  

Official title:

A Multinational, Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Controlled Study Followed by an Active Treatment Period, to Evaluate the Efficacy, Safety and Tolerability of Two Doses of Oral Administration of Laquinimod (0.6 mg/Day or 1.2 mg/Day) in Patients With Relapsing Remitting Multiple Sclerosis (RRMS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01707992
• Other study ID #: LAQ-MS-305
• Secondary ID: 2012-003647-30
• Status: Completed
• Phase: Phase 3
• Start date: February 20, 2013
• Est. completion date: July 4, 2017

Study information

• Verified date: November 2021
• Source: Teva Branded Pharmaceutical Products R&D, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study followed by active treatment, to evaluate the efficacy, safety and tolerability of two doses of oral administration of laquinimod in participants with RRMS. The study has 2 periods: Period 1, the double-blind, placebo-controlled period (up to 24 months) and Period 2, the active treatment period (24 months).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2199
• Est. completion date: July 4, 2017
• Est. primary completion date: April 13, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Participants must have a confirmed and documented multiple sclerosis (MS) diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.
• Participants must be ambulatory with Kurtzke's expanded disability status scale (EDSS) score of 0 to 5.5 in both screening and randomization visits.
• Participants must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)/oral] or adrenocorticotrophic hormone, 60 days prior to randomization.
• Participants must have experienced at least one documented relapse in the 12 months prior to randomization.
• Participants must have disease duration of not more than 15 years.
• Women of child-bearing potential (for example, women who are not postmenopausal or surgically sterilized) must practice an acceptable method of birth control for 30 days before taking the study drug and two acceptable methods of birth control during the duration of the study and until 30 days after the last dose of study medication.
• Additional criteria apply, please contact the investigator for more information.

Exclusion Criteria:

• Participants with progressive forms of MS.
• Participants with neuromyelitis optica.
• Use of experimental or investigational drugs and/or participation in drug clinical studies within the 6 months prior to randomization.
• Use of immunosuppressive agents or cytotoxic agents, including cyclophosphamide, within 6 months prior to randomization.
• Use of either of the following within 2 years prior to randomization visit:

natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.

• Use of teriflunomide (Aubagio®) within 2 years prior to randomization, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to randomization.
• Previous treatment with glatiramer acetate (Copaxone®) Interferon ß (either 1a or 1b), fingolimod (Gilenya®), dimethyl fumarate (Tecfidera®) or intravenous immunoglobulins within 2 months prior to randomization.
• Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.
• Previous use of mitoxantrone (Novantrone®), cladribine, or alemtuzumab (Lemtrada®).
• Previous use of laquinimod.
• Previous total body irradiation or total lymphoid irradiation.
• Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
• Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to randomization.
• Use of inducers of CYP3A4 within 2 weeks prior to randomization visit.
• Pregnancy or breastfeeding.
• A known history of sensitivity to gadolinium (Gd).
• Inability to successfully undergo magnetic resonance imaging (MRI) scanning.
• Participants who underwent endovascular treatment for chronic cerebrospinal venous insufficiency within 3 months prior to randomization.
• Additional criteria apply, please contact the investigator for more information.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Sclerosis

Intervention

Drug:
• Laquinimod
Laquinimod will be administered as per the dose and schedule specified in the respective arms.
• Placebo
Placebo matching to laquinimod will be administered as per the schedule specified in the respective arms.

Locations

Country	Name	City	State
Austria	Teva Investigational Site 33013	Innsbruck
Austria	Teva Investigational Site 33014	Linz
Austria	Teva Investigational Site 33015	Wien
Austria	Teva Investigational Site 33016	Wien
Belarus	Teva Investigational Site 68010	Gomel
Belarus	Teva Investigational Site 68013	Grodno
Belarus	Teva Investigational Site 68008	Minsk
Belarus	Teva Investigational Site 68009	Minsk
Belarus	Teva Investigational Site 68012	Minsk
Belarus	Teva Investigational Site 68011	Vitebsk
Belgium	Teva Investigational Site 37023	Charleroi
Belgium	Teva Investigational Site 37024	Sijsele
Bosnia and Herzegovina	Teva Investigational Site 69008	Mostar
Bosnia and Herzegovina	Teva Investigational Site 69006	Sarajevo
Bosnia and Herzegovina	Teva Investigational Site 69009	Tuzla
Bulgaria	Teva Investigational Site 59039	Pleven
Bulgaria	Teva Investigational Site 59040	Pleven
Bulgaria	Teva Investigational Site 59060	Pleven
Bulgaria	Teva Investigational Site 59062	Plovdiv
Bulgaria	Teva Investigational Site 59061	Ruse
Bulgaria	Teva Investigational Site 59055	Shumen
Bulgaria	Teva Investigational Site 59038	Sofia
Bulgaria	Teva Investigational Site 59041	Sofia
Bulgaria	Teva Investigational Site 59042	Sofia
Bulgaria	Teva Investigational Site 59043	Sofia
Bulgaria	Teva Investigational Site 59044	Sofia
Bulgaria	Teva Investigational Site 59045	Sofia
Bulgaria	Teva Investigational Site 59048	Sofia
Bulgaria	Teva Investigational Site 59050	Sofia
Bulgaria	Teva Investigational Site 59052	Sofia
Bulgaria	Teva Investigational Site 59054	Sofia
Bulgaria	Teva Investigational Site 59057	Sofia
Bulgaria	Teva Investigational Site 59058	Sofia
Bulgaria	Teva Investigational Site 59059	Sofia
Bulgaria	Teva Investigational Site 59063	Sofia
Bulgaria	Teva Investigational Site 59049	Stara Zagora
Bulgaria	Teva Investigational Site 59046	Varna
Bulgaria	Teva Investigational Site 59051	Veliko Tarnovo
Bulgaria	Teva Investigational Site 59053	Veliko Tarnovo
Canada	Teva Investigational Site 11014	Burnaby	British Columbia
Canada	Teva Investigational Site 11013	Edmonton	Alberta
Canada	Teva Investigational Site 11015	Ottawa
Canada	Teva Investigational Site 11016	Saskatoon
Croatia	Teva Investigational Site 60010	Osijek
Croatia	Teva Investigational Site 60011	Varazdin
Croatia	Teva Investigational Site 60009	Zagreb
Czechia	Teva Investigational Site 54042	Brno
Czechia	Teva Investigational Site 54043	Havirov
Czechia	Teva Investigational Site 54047	Hradec Kralove 3
Czechia	Teva Investigational Site 54046	Jihlava
Czechia	Teva Investigational Site 54044	Olomouc
Czechia	Teva Investigational Site 54045	Ostrava
Czechia	Teva Investigational Site 54041	Praha
Czechia	Teva Investigational Site 54049	Praha 10
Czechia	Teva Investigational Site 54048	Teplice
Estonia	Teva Investigational Site 55005	Parnu
Estonia	Teva Investigational Site 55006	Tallinn
Estonia	Teva Investigational Site 55008	Tallinn
Estonia	Teva Investigational Site 55007	Tartu
France	Teva Investigational Site 35075	Clermont-Ferrand Cedex 1
France	Teva Investigational Site 35077	Dijon
France	Teva Investigational Site 35073	Lille
France	Teva Investigational Site 35076	Lyon cedex 04
France	Teva Investigational Site 35079	Nimes
Georgia	Teva Investigational Site 81014	Tbilisi
Georgia	Teva Investigational Site 81015	Tbilisi
Georgia	Teva Investigational Site 81016	Tbilisi
Georgia	Teva Investigational Site 81017	Tbilisi
Georgia	Teva Investigational Site 81018	Tbilisi
Georgia	Teva Investigational Site 81019	Tbilisi
Germany	Teva Investigational Site 32199	Bad Mergentheim
Germany	Teva Investigational Site 32195	Berg
Germany	Teva Investigational Site 32174	Berlin
Germany	Teva Investigational Site 32176	Berlin
Germany	Teva Investigational Site 32186	Berlin
Germany	Teva Investigational Site 32198	Berlin
Germany	Teva Investigational Site 32200	Berlin
Germany	Teva Investigational Site 32177	Bochum
Germany	Teva Investigational Site 32193	Dresden
Germany	Teva Investigational Site 32184	Erbach
Germany	Teva Investigational Site 32189	Erfurt
Germany	Teva Investigational Site 32203	Giessen
Germany	Teva Investigational Site 32202	Goettigen
Germany	Teva Investigational Site 32196	Halle (Saale)
Germany	Teva Investigational Site 32179	Hamburg
Germany	Teva Investigational Site 32181	Hamburg
Germany	Teva Investigational Site 32182	Hannover
Germany	Teva Investigational Site 32175	Ibbenburen
Germany	Teva Investigational Site 32201	Jena
Germany	Teva Investigational Site 32183	Koln
Germany	Teva Investigational Site 32190	Leipzig
Germany	Teva Investigational Site 32185	Magdeburg
Germany	Teva Investigational Site 32191	Rostock
Germany	Teva Investigational Site 32194	Teupitz
Germany	Teva Investigational Site 32173	Ulm
Germany	Teva Investigational Site 32197	Wermsdorf
Germany	Teva Investigational Site 32188	Westerstede
Greece	Teva Investigational Site 63024	Athens
Greece	Teva Investigational Site 63027	Athens
Greece	Teva Investigational Site 63029	Chaidari
Greece	Teva Investigational Site 63026	Heraklion
Greece	Teva Investigational Site 63030	Larisa
Greece	Teva Investigational Site 63025	Thessaloniki
Greece	Teva Investigational Site 63028	Thessaloniki
Hungary	Teva Investigational Site 51046	Budapest
Hungary	Teva Investigational Site 51043	Debrecen
Hungary	Teva Investigational Site 51045	Eger
Hungary	Teva Investigational Site 51044	Kaposvar
Israel	Teva Investigational Site 80023	Haifa
Israel	Teva Investigational Site 80024	Haifa
Israel	Teva Investigational Site 80020	Ramat Gan
Israel	Teva Investigational Site 80021	Tel Aviv
Italy	Teva Investigational Site 30037	Bologna
Italy	Teva Investigational Site 30031	Castelfiorentino
Italy	Teva Investigational Site 30030	Cefalu
Italy	Teva Investigational Site 30032	Chieti
Italy	Teva Investigational Site 30024	Firenze
Italy	Teva Investigational Site 30029	Gallarate
Italy	Teva Investigational Site 30023	Milano
Italy	Teva Investigational Site 30039	Milano
Italy	Teva Investigational Site 30034	Napoli
Italy	Teva Investigational Site 30027	Palermo
Italy	Teva Investigational Site 30025	Rome
Italy	Teva Investigational Site 30026	Rome
Italy	Teva Investigational Site 30028	Rome
Italy	Teva Investigational Site 30035	Rome
Italy	Teva Investigational Site 30040	Verona
Korea, Republic of	Teva Investigational Site 87001	Goyang-si
Korea, Republic of	Teva Investigational Site 87002	Seoul
Korea, Republic of	Teva Investigational Site 87003	Seoul
Latvia	Teva Investigational Site 56005	Riga
Latvia	Teva Investigational Site 56006	Riga
Moldova, Republic of	Teva Investigational Site 70005	Chisinau
Moldova, Republic of	Teva Investigational Site 70006	Chisinau
Moldova, Republic of	Teva Investigational Site 70008	Chisinau
Montenegro	Teva Investigational Site 66002	Podgorica
North Macedonia	Teva Investigational Site 65010	Skopje
North Macedonia	Teva Investigational Site 65011	Skopje
North Macedonia	Teva Investigational Site 65012	Skopje
Poland	Teva Investigational Site 53066	Bialystok
Poland	Teva Investigational Site 53071	Bialystok
Poland	Teva Investigational Site 53085	Bydgoszcz
Poland	Teva Investigational Site 53084	Czestochowa
Poland	Teva Investigational Site 53067	Gdansk
Poland	Teva Investigational Site 53069	Gdansk
Poland	Teva Investigational Site 53083	Gdansk
Poland	Teva Investigational Site 53078	Grodzisk Mazowiecki
Poland	Teva Investigational Site 53070	Katowice
Poland	Teva Investigational Site 53073	Katowice
Poland	Teva Investigational Site 53074	Katowice
Poland	Teva Investigational Site 53080	Katowice
Poland	Teva Investigational Site 53081	Katowice
Poland	Teva Investigational Site 53064	Konskie
Poland	Teva Investigational Site 53065	Konstancin-Jeziorna
Poland	Teva Investigational Site 53072	Koscierzyna
Poland	Teva Investigational Site 53063	Lodz
Poland	Teva Investigational Site 53079	Olsztyn
Poland	Teva Investigational Site 53068	Plewiska
Poland	Teva Investigational Site 53076	Szczecin
Romania	Teva Investigational Site 52045	Balotesti
Romania	Teva Investigational Site 52041	Bucharest
Romania	Teva Investigational Site 52034	Bucuresti
Romania	Teva Investigational Site 52037	Bucuresti
Romania	Teva Investigational Site 52050	Bucuresti
Romania	Teva Investigational Site 52036	Cluj-Napoca
Romania	Teva Investigational Site 52040	Cluj-Napoca
Romania	Teva Investigational Site 52038	Constanta
Romania	Teva Investigational Site 52044	Constanta
Romania	Teva Investigational Site 52048	Craiova
Romania	Teva Investigational Site 52049	Hunedoara
Romania	Teva Investigational Site 52042	Iasi
Romania	Teva Investigational Site 52039	Oradea
Romania	Teva Investigational Site 52047	Piatra-Neamt
Romania	Teva Investigational Site 52046	Sibiu
Romania	Teva Investigational Site 52035	Targu Mures
Romania	Teva Investigational Site 52043	Timisoara
Russian Federation	Teva Investigational Site 50130	Barnaul
Russian Federation	Teva Investigational Site 50129	Chelyabinsk
Russian Federation	Teva Investigational Site 50208	Kazan
Russian Federation	Teva Investigational Site 50148	Kemerovo
Russian Federation	Teva Investigational Site 50144	Krasnodar
Russian Federation	Teva Investigational Site 50124	Moscow
Russian Federation	Teva Investigational Site 50133	Moscow
Russian Federation	Teva Investigational Site 50146	Moscow
Russian Federation	Teva Investigational Site 50147	Moscow
Russian Federation	Teva Investigational Site 50128	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50131	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50141	Nizhny Novgorod
Russian Federation	Teva Investigational Site 50127	Perm
Russian Federation	Teva Investigational Site 50143	Rostov-on-Don
Russian Federation	Teva Investigational Site 50149	Rostov-on-Don
Russian Federation	Teva Investigational Site 50126	Saint Petersburg
Russian Federation	Teva Investigational Site 50140	Saint Petersburg
Russian Federation	Teva Investigational Site 50138	Samara
Russian Federation	Teva Investigational Site 50135	Saratov
Russian Federation	Teva Investigational Site 50136	Smolensk
Russian Federation	Teva Investigational Site 50137	St. Petersburg
Russian Federation	Teva Investigational Site 50125	Tomsk
Russian Federation	Teva Investigational Site 50139	Tyumen
Russian Federation	Teva Investigational Site 50134	Ufa
Russian Federation	Teva Investigational Site 50132	Volgograd
Russian Federation	Teva Investigational Site 50142	Yaroslavl
Serbia	Teva Investigational Site 61024	Belgrade
Serbia	Teva Investigational Site 61025	Belgrade
Serbia	Teva Investigational Site 61027	Belgrade
Serbia	Teva Investigational Site 61018	Cacak
Serbia	Teva Investigational Site 61015	Kragujevac
Serbia	Teva Investigational Site 61014	Nis
Serbia	Teva Investigational Site 61019	Sombor
Serbia	Teva Investigational Site 61016	Subotica
Serbia	Teva Investigational Site 61017	Uzice
Serbia	Teva Investigational Site 61022	Valjevo
Serbia	Teva Investigational Site 61026	Vrbas
Serbia	Teva Investigational Site 61021	Zrenjanin
Slovakia	Teva Investigational Site 62012	Hlohovec
Slovakia	Teva Investigational Site 62013	Trnava
Spain	Teva Investigational Site 31030	Barcelona
Spain	Teva Investigational Site 31035	Barcelona
Spain	Teva Investigational Site 31031	Getafe
Spain	Teva Investigational Site 31036	L'Hospitalet de Llobregat
Spain	Teva Investigational Site 31032	Madrid
Spain	Teva Investigational Site 31034	Madrid
Spain	Teva Investigational Site 31033	Navarro
Spain	Teva Investigational Site 31039	Oviedo
Spain	Teva Investigational Site 31037	Salt
Ukraine	Teva Investigational Site 58087	Chernihiv
Ukraine	Teva Investigational Site 58083	Chernivtsi
Ukraine	Teva Investigational Site 58077	Dnipropetrovsk
Ukraine	Teva Investigational Site 58076	Ivano-Frankivsk
Ukraine	Teva Investigational Site 58088	Ivano-Frankivsk
Ukraine	Teva Investigational Site 58084	Kharkiv
Ukraine	Teva Investigational Site 58116	Kharkiv
Ukraine	Teva Investigational Site 58089	Kiev
Ukraine	Teva Investigational Site 58073	Kyiv
Ukraine	Teva Investigational Site 58078	Kyiv
Ukraine	Teva Investigational Site 58081	Kyiv
Ukraine	Teva Investigational Site 58086	Lviv
Ukraine	Teva Investigational Site 58115	Lviv
Ukraine	Teva Investigational Site 58074	Odesa
Ukraine	Teva Investigational Site 58085	Odessa
Ukraine	Teva Investigational Site 58082	Poltava
Ukraine	Teva Investigational Site 58080	Simferopol
Ukraine	Teva Investigational Site 58072	Vinnytsya
Ukraine	Teva Investigational Site 58075	Zaporizhzhya
Ukraine	Teva Investigational Site 58079	Zaporizhzhya
United Kingdom	Teva Investigational Site 34015	Glasgow
United Kingdom	Teva Investigational Site 34010	Liverpool
United Kingdom	Teva Investigational Site 34011	Liverpool
United Kingdom	Teva Investigational Site 34019	London
United Kingdom	Teva Investigational Site 34016	Salford
United Kingdom	Teva Investigational Site 34017	Sheffield
United Kingdom	Teva Investigational Site 34013	Stoke-on-Trent
United States	Teva Investigational Site 10346	Advance	North Carolina
United States	Teva Investigational Site 10307	Aurora	Colorado
United States	Teva Investigational Site 10309	Bellevue	Ohio
United States	Teva Investigational Site 10338	Boston	Massachusetts
United States	Teva Investigational Site 10334	Centennial	Colorado
United States	Teva Investigational Site 10350	Chicago	Illinois
United States	Teva Investigational Site 10317	Columbus	Ohio
United States	Teva Investigational Site 10316	Coral Gables	Florida
United States	Teva Investigational Site 10313	Cordova	Tennessee
United States	Teva Investigational Site 10329	Cullman	Alabama
United States	Teva Investigational Site 10325	Dayton	Ohio
United States	Teva Investigational Site 10345	Evanston	Illinois
United States	Teva Investigational Site 10332	Fort Collins	Colorado
United States	Teva Investigational Site 10339	Fort Wayne	Indiana
United States	Teva Investigational Site 10324	Franklin	Tennessee
United States	Teva Investigational Site 10310	Fresno	California
United States	Teva Investigational Site 10340	Hershey	Pennsylvania
United States	Teva Investigational Site 10348	Lenexa	Kansas
United States	Teva Investigational Site 10318	Nashville	Tennessee
United States	Teva Investigational Site 10330	Newport News	Virginia
United States	Teva Investigational Site 10343	Northbrook	Illinois
United States	Teva Investigational Site 10331	Philadelphia	Pennsylvania
United States	Teva Investigational Site 10311	Roanoke	Virginia
United States	Teva Investigational Site 10341	Saint Petersburg	Florida
United States	Teva Investigational Site 10319	Salt Lake City	Utah
United States	Teva Investigational Site 10308	Sarasota	Florida
United States	Teva Investigational Site 10335	Seattle	Washington
United States	Teva Investigational Site 10349	Sun City	Arizona
United States	Teva Investigational Site 10315	Sunrise	Florida
United States	Teva Investigational Site 10323	Tampa	Florida
United States	Teva Investigational Site 10342	Tucson	Arizona
United States	Teva Investigational Site 10347	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Teva Branded Pharmaceutical Products R&D, Inc.

Countries where clinical trial is conducted

United States,  Austria,  Belarus,  Belgium,  Bosnia and Herzegovina,  Bulgaria,  Canada,  Croatia,  Czechia,  Estonia,  France,  Georgia,  Germany,  Greece,  Hungary,  Israel,  Italy,  Korea, Republic of,  Latvia,  Moldova, Republic of,  Montenegro,  North Macedonia,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Spain,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Placebo-Controlled Phase: Number of Participants With Adverse Events (AEs)	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.	Baseline up to Month 24
Other	Active-Treatment Phase: Number of Participants With AEs	An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. SAE was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs included both SAEs and non-serious AEs.	Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Other	Placebo-Controlled Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities	Clinically significant vital signs abnormalities included: Pulse rate: greater than or equal to (>=) 120 beats per minute (bpm) and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 millimeters of mercury (mmHg) and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.	Baseline up to Week 24
Other	Active-Treatment Phase: Number of Participants With Clinically Significant Vital Signs Abnormalities	Clinically significant vital signs abnormalities included: Pulse rate: >=120 bpm and increase from baseline of >=30 bpm, <=45 bpm and decrease from baseline of >=30 bpm; Systolic blood pressure: >=180 mmHg and increase from baseline of >=30 mmHg, <=90 and decrease from baseline of >=30 mmHg; Diastolic blood pressure: >=100 mmHg and increase from baseline of >=20 mmHg, <=50 mmHg and decrease from baseline of >=20 mmHg.	Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Other	Placebo-Controlled Phase: Number of Participants With Shift From Baseline to Endpoint in Electrocardiogram (ECG) Parameters	ECG parameters included: PR interval, QRS interval, QT interval corrected using the Fridericia formula (QTcF) and QT interval corrected using the Bazett's formula (QTcB). Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.	Baseline, Endpoint (Month 24)
Other	Active Treatment Phase: Number of Participants With Shift From Baseline to Endpoint in ECG Parameters	ECG parameters included: PR interval, QRS interval, QTcF and QTcB. Shifts represented as Baseline - endpoint value (last observed post-baseline value). Abnormal NCS indicated an abnormal but not clinically significant finding. Abnormal CS indicated an abnormal and clinically significant finding.	Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase), endpoint (Month 24 of active-treatment phase)
Other	Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry	Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 millimoles per liter (mmol/L); Alanine aminotransferase (ALT) (in units per liter [U/L]), aspartate aminotransferase (AST) (in U/L), alkaline phosphatase (in U/L), gamma-glutamyltransferase (GGT) (in U/L), creatine phosphokinase (CPK) (in U/L), C-reactive protein (CRP) (in milligrams per liter [mg/L]), pancreatic amylase (in U/L)>=3 * upper limit of normal (ULN); Fibrinogen >=6 grams per liter (gm/L); Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L.	Baseline up to Month 24
Other	Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Serum Chemistry	Potentially clinically significant serum chemistry abnormalities included: Glucose <=3 and >=13.88 mmol/L; ALT (in U/L), AST (in U/L), alkaline phosphatase (in U/L), GGT (in U/L), CPK (in U/L), CRP (in mg/L), pancreatic amylase (in U/L)>=3 * ULN; Fibrinogen >=6 gm/L; Sodium <=130 and >=150 mmol/L; Potassium <=3.2 and >=5.5 mmol/L; Calcium <=1.87 and >=2.75 mmol/L; Phosphate <=0.65 and >=1.61 mmol/L; Blood urea nitrogen (in mmol/L); Total bilirubin >=28 micromols per liter (micromols/L); Creatinine >=117 micromols/L; Albumin <=25 gm/L.	Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Other	Placebo-Controlled Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values	Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5 grams per deciliter (gm/dL) in males and <=10 gm/dL in females; White blood cells (WBCs) count <=2.5 and >=21*10^9 per liter (L); Absolute neutrophil count (ANC) <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.	Baseline up to Month 24
Other	Active Treatment Phase: Number of Participants With Potentially Clinically Significant Abnormal Hematology Values	Potentially clinically significant hematological abnormalities included: Hemoglobin <=11.5, >=20 gm/dL in males, and <=10, >=18.5 gm/dL in females; WBCs count <=2.5 and >=21*10^9 per L; ANC <=1.49*10^9 per L; Platelet count <=100 and >=600*10^9 per L.	Baseline (Month 0 of active-treatment phase/Month 24 of placebo-controlled phase) up to Month 24 of active-treatment phase
Primary	Placebo-Controlled Phase: Time to Confirmed Disease Progression (CDP) Confirmed After At Least 3 Months (Number of Participants With CDP After At Least 3 Months)	Time to CDP was defined as the time to a sustained increase in Kurtzke's Expanded Disability Status Scale (EDSS) score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least three months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to multiple sclerosis [MS]). Data is presented as distribution of CDP (number of participants with CDP) sustained for 3 months.	Baseline to Month 24
Secondary	Placebo-Controlled Phase: Percent Change From Baseline in Brain Volume at Month 15	Brain atrophy was defined by the percent change in brain volume from baseline to Month 15. For participants who prematurely discontinued treatment or completed the placebo-controlled phase before Month 15, the last available measurement was used, provided it was performed at least 9 months following the initiation of study drug.	Baseline, Month 15
Secondary	Placebo-Controlled Phase: Time to First Confirmed Relapse (Number of Participants With Confirmed Relapse)	Relapse was defined as appearance of one or more new neurological abnormalities or reappearance or worsening of one or more previously observed neurological abnormalities, lasting for at least 48 hours (in absence of fever or any infection) and immediately preceded by an improving neurological state of at least 30 days from onset of previous relapse. An event was counted as a relapse only when the participant's symptoms were accompanied by observed objective neurological changes, consistent with an increase of at least 0.5 in EDSS; or one grade in score of 2 or more of 7 Functional Systems (FS) (excluding changes in bowel or bladder function or cognition); or 2 grades in score of one of the FS as compared to previous evaluation. EDSS assesses disability in 8 FS with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of relapsing participants (number of participants with confirmed relapse).	Baseline to Month 24
Secondary	Placebo-Controlled Phase: Time to CDP Confirmed After At Least 6 Months (Number of Participants With CDP After At Least 6 Months)	Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 6 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 6 months.	Baseline to Month 24
Secondary	Placebo-Controlled Phase: Time to CDP Confirmed After At Least 9 Months (Number of Participants With Confirmed Relapse After At Least 9 Months)	Time to CDP was defined as the time to a sustained increase in Kurtzke's EDSS score of at least 1 point if baseline EDSS score was less than or equal to 5.0, or at least 0.5 point if the baseline EDSS score was 5.5, over a period of at least 9 months. EDSS assesses disability in 8 functional systems with an overall score ranging from 0 (normal) to 10 (death due to MS). Data is presented as distribution of CDP (number of participants with CDP) sustained for 9 months.	Baseline to Month 24