Exploring the Efficacy and Safety of Siponimod in Patients With Secondary Progressive Multiple Sclerosis (EXPAND)

Secondary Progressive Multiple Sclerosis Clinical Trial

Official title:

A Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Variable Treatment Duration Study Evaluating the Efficacy and Safety of Siponimod (BAF312) in Patients With Secondary Progressive Multiple Sclerosis Followed by Extended Treatment With Open-label BAF312.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01665144
• Other study ID #: CBAF312A2304
• Secondary ID: 2012-003056-36
• Status: Completed
• Phase: Phase 3
• Start date: December 20, 2012
• Est. completion date: March 31, 2023

Study information

• Verified date: May 2024
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Evaluate the safety and efficacy of Siponimod (BAF312) versus placebo in a variable treatment duration in patients with secondary progressive multiple sclerosis (Core Part) followed by extended treatment with open-label BAF312 to obtain data on long-term safety, tolerability and efficacy (Extension Part).

Description:

This study had two parts, a Core Part and an Extension Part. The Core Part of the study was a randomized, multicenter, double-blind, placebo-controlled parallel-group study in patients with secondary progressive multiple sclerosis (SPMS). Eligible patients were randomized (2:1) to receive either siponimod or placebo. The duration of the Core Part of the study was variable for each patient, given that this was an event-driven study and terminated when a pre-defined number of confirmed disability progression (CDP) events had occurred irrespective of duration of individual patient participation. Patients who had 6-month CDP during the Treatment Epoch of the Core Part were provided with options that included starting treatment with open label siponimod as rescue medication. Patients who were eligible to enter the Extension Part received open label siponimod.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1651
• Est. completion date: March 31, 2023
• Est. primary completion date: April 29, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Prior history of relapsing remitting MS
• SPMS defined as progressive increase of disability over at least 6 months
• EDSS score of 3.0 to 6.5
• No relapse of corticosteroid treatment within 3 months

Exclusion Criteria:

• Women of child bearing potential must use reliable forms of contraception.
• Diagnosis of Macular edema during screening period
• Any medically unstable condition determined by investigator.
• Unable to undergo MRI scans
• Hypersensitivity to any study drugs or drugs of similar class

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Chronic Progressive
• Neoplasm Metastasis
• Sclerosis
• Secondary Progressive Multiple Sclerosis

Intervention

Drug:
• BAF312
0.25, 0.5, 1, and 2 mg film-coated tablets
• Placebo
Film-coated tablets

Locations

Country	Name	City	State
Argentina	Novartis Investigative Site	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Caba	Buenos Aires
Argentina	Novartis Investigative Site	Capital Federal	Buenos Aires
Argentina	Novartis Investigative Site	Cordoba
Australia	Novartis Investigative Site	Camperdown	New South Wales
Australia	Novartis Investigative Site	Heidelberg	Victoria
Australia	Novartis Investigative Site	Kogarah	New South Wales
Australia	Novartis Investigative Site	Liverpool	New South Wales
Australia	Novartis Investigative Site	Parkville	Victoria
Austria	Novartis Investigative Site	Klagenfurt
Austria	Novartis Investigative Site	Vienna
Austria	Novartis Investigative Site	Wien
Belgium	Novartis Investigative Site	Brugge
Belgium	Novartis Investigative Site	Bruxelles
Belgium	Novartis Investigative Site	Edegem	Antwerpen
Belgium	Novartis Investigative Site	Fraiture En Condroz
Belgium	Novartis Investigative Site	Gent
Belgium	Novartis Investigative Site	Leuven
Belgium	Novartis Investigative Site	Pelt
Belgium	Novartis Investigative Site	Sijsele
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Sofia
Bulgaria	Novartis Investigative Site	Varna
Canada	Novartis Investigative Site	Burnaby	British Columbia
Canada	Novartis Investigative Site	Calgary	Alberta
Canada	Novartis Investigative Site	Edmonton	Alberta
Canada	Novartis Investigative Site	Greenfield Park	Quebec
Canada	Novartis Investigative Site	Halifax	Nova Scotia
Canada	Novartis Investigative Site	Kingston	Ontario
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Montreal	Quebec
Canada	Novartis Investigative Site	Ottawa	Ontario
Canada	Novartis Investigative Site	Toronto	Ontario
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Beijing
China	Novartis Investigative Site	Changchun	Jilin
China	Novartis Investigative Site	Chengdu	Sichuan
China	Novartis Investigative Site	Shanghai
China	Novartis Investigative Site	Taiyuan	Shanxi
China	Novartis Investigative Site	XI An	Shanxi
Czechia	Novartis Investigative Site	Brno	Czech Rep.
Czechia	Novartis Investigative Site	JIhlava
Czechia	Novartis Investigative Site	Prague 5
Czechia	Novartis Investigative Site	Praha
Czechia	Novartis Investigative Site	Teplice	Czech Republic
Estonia	Novartis Investigative Site	Tallinn
Estonia	Novartis Investigative Site	Tallinn
France	Novartis Investigative Site	Bordeaux Cedex
France	Novartis Investigative Site	Caen
France	Novartis Investigative Site	Lille
France	Novartis Investigative Site	Marseille Cedex 05
France	Novartis Investigative Site	Montpellier
France	Novartis Investigative Site	Nancy
France	Novartis Investigative Site	Nimes
France	Novartis Investigative Site	Paris 13
France	Novartis Investigative Site	Rennes
France	Novartis Investigative Site	St Herblain
France	Novartis Investigative Site	Strasbourg
Germany	Novartis Investigative Site	Aschaffenburg
Germany	Novartis Investigative Site	Bad Mergentheim
Germany	Novartis Investigative Site	Bayreuth
Germany	Novartis Investigative Site	Berg
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Berlin
Germany	Novartis Investigative Site	Bielefeld
Germany	Novartis Investigative Site	Boblingen
Germany	Novartis Investigative Site	Bochum
Germany	Novartis Investigative Site	Bonn
Germany	Novartis Investigative Site	Dresden
Germany	Novartis Investigative Site	Erbach
Germany	Novartis Investigative Site	Erlangen
Germany	Novartis Investigative Site	Frankfurt
Germany	Novartis Investigative Site	Freiburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hamburg
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Hannover
Germany	Novartis Investigative Site	Heidelberg
Germany	Novartis Investigative Site	Homburg
Germany	Novartis Investigative Site	Itzehoe
Germany	Novartis Investigative Site	Jena
Germany	Novartis Investigative Site	Kassel
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Leipzig
Germany	Novartis Investigative Site	Muenchen
Germany	Novartis Investigative Site	Muenster
Germany	Novartis Investigative Site	Neuburg an der Donau
Germany	Novartis Investigative Site	Oldenburg
Germany	Novartis Investigative Site	Potsdam
Germany	Novartis Investigative Site	Prien
Germany	Novartis Investigative Site	Regensburg	Bavaria
Germany	Novartis Investigative Site	Rostock
Germany	Novartis Investigative Site	Schwendi
Germany	Novartis Investigative Site	Siegen
Germany	Novartis Investigative Site	Stade
Germany	Novartis Investigative Site	Stadtroda
Germany	Novartis Investigative Site	Teupitz
Germany	Novartis Investigative Site	Tuebingen
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Ulm
Germany	Novartis Investigative Site	Unterhaching
Germany	Novartis Investigative Site	Wiesbaden
Germany	Novartis Investigative Site	Wuerzburg
Greece	Novartis Investigative Site	Athens
Greece	Novartis Investigative Site	Heraklion Crete
Greece	Novartis Investigative Site	Thessaloniki
Hungary	Novartis Investigative Site	Balassagyarmat
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest
Hungary	Novartis Investigative Site	Budapest	HUN
Hungary	Novartis Investigative Site	Eger
Hungary	Novartis Investigative Site	Esztergom	HUN
Hungary	Novartis Investigative Site	Miskolc
Hungary	Novartis Investigative Site	Nyiregyhaza
Hungary	Novartis Investigative Site	Veszprem
Ireland	Novartis Investigative Site	Dublin 4
Ireland	Novartis Investigative Site	Dublin 9
Israel	Novartis Investigative Site	Jerusalem
Israel	Novartis Investigative Site	Ramat Gan
Italy	Novartis Investigative Site	Cefalu	PA
Italy	Novartis Investigative Site	Genova	GE
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Milano	MI
Italy	Novartis Investigative Site	Napoli
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Italy	Novartis Investigative Site	Roma	RM
Japan	Novartis Investigative Site	Aomori
Japan	Novartis Investigative Site	Asahikawa-city	Hokkaido
Japan	Novartis Investigative Site	Chiba
Japan	Novartis Investigative Site	Kawagoe	Saitama
Japan	Novartis Investigative Site	Kodaira	Tokyo
Japan	Novartis Investigative Site	Kyoto-city	Kyoto
Japan	Novartis Investigative Site	Morioka	Iwate
Japan	Novartis Investigative Site	Osaka
Japan	Novartis Investigative Site	Ota-ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku ku	Tokyo
Japan	Novartis Investigative Site	Shinjuku-ku	Tokyo
Japan	Novartis Investigative Site	Suita	Osaka
Japan	Novartis Investigative Site	Tokorozawa city	Saitama
Japan	Novartis Investigative Site	Toon city	Ehime
Latvia	Novartis Investigative Site	Riga	LV
Latvia	Novartis Investigative Site	Riga
Latvia	Novartis Investigative Site	Riga
Lithuania	Novartis Investigative Site	Kaunas	LTU
Lithuania	Novartis Investigative Site	Klaipeda
Lithuania	Novartis Investigative Site	Vilnius
Netherlands	Novartis Investigative Site	Amsterdam
Netherlands	Novartis Investigative Site	Breda
Netherlands	Novartis Investigative Site	Eindhoven
Netherlands	Novartis Investigative Site	Hoorn
Netherlands	Novartis Investigative Site	Sittard-Geleen
Netherlands	Novartis Investigative Site	Tilburg
Poland	Novartis Investigative Site	Grudziadz
Poland	Novartis Investigative Site	Katowice
Poland	Novartis Investigative Site	Kielce
Poland	Novartis Investigative Site	Konskie
Poland	Novartis Investigative Site	Krakow
Poland	Novartis Investigative Site	Lodz
Poland	Novartis Investigative Site	Poznan
Poland	Novartis Investigative Site	Warszawa
Portugal	Novartis Investigative Site	Amadora
Portugal	Novartis Investigative Site	Braga
Portugal	Novartis Investigative Site	Coimbra
Portugal	Novartis Investigative Site	Lisboa
Portugal	Novartis Investigative Site	Porto
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Bucharest
Romania	Novartis Investigative Site	Constanta
Romania	Novartis Investigative Site	Suceava
Romania	Novartis Investigative Site	Targu Mures
Romania	Novartis Investigative Site	Timisoara
Russian Federation	Novartis Investigative Site	Barnaul
Russian Federation	Novartis Investigative Site	Kazan
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Moscow
Russian Federation	Novartis Investigative Site	Novosibirsk
Russian Federation	Novartis Investigative Site	Saint Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	St. Petersburg
Russian Federation	Novartis Investigative Site	Ufa
Slovakia	Novartis Investigative Site	Banska Bystrica
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Bratislava
Slovakia	Novartis Investigative Site	Martin
Slovakia	Novartis Investigative Site	Nitra
Slovakia	Novartis Investigative Site	Presov
Slovakia	Novartis Investigative Site	Trencin
Slovakia	Novartis Investigative Site	Trnava
Spain	Novartis Investigative Site	Badalona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona	Catalunya
Spain	Novartis Investigative Site	Barcelona
Spain	Novartis Investigative Site	Bilbao	Pais Vasco
Spain	Novartis Investigative Site	El Palmar	Murcia
Spain	Novartis Investigative Site	Hospitalet de Llobregat	Barcelona
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Madrid
Spain	Novartis Investigative Site	Malaga	Andalucia
Spain	Novartis Investigative Site	San Sebastian	Pais Vasco
Spain	Novartis Investigative Site	Sevilla	Andalucia
Spain	Novartis Investigative Site	Valencia	Comunidad Valenciana
Spain	Novartis Investigative Site	Valencia
Sweden	Novartis Investigative Site	Goeteborg
Sweden	Novartis Investigative Site	Stockholm
Sweden	Novartis Investigative Site	Stockholm
Switzerland	Novartis Investigative Site	Aarau	CH
Switzerland	Novartis Investigative Site	Basel
Switzerland	Novartis Investigative Site	Lausanne
Switzerland	Novartis Investigative Site	Lugano
Switzerland	Novartis Investigative Site	Luzern
Switzerland	Novartis Investigative Site	St Gallen
Switzerland	Novartis Investigative Site	Zuerich
Turkey	Novartis Investigative Site	Altunizade
Turkey	Novartis Investigative Site	Haseki Istanbul
Turkey	Novartis Investigative Site	Istanbul	TUR
Turkey	Novartis Investigative Site	Kocaeli
Turkey	Novartis Investigative Site	Mecidiyekoy Istanbul
Turkey	Novartis Investigative Site	Samsun
Turkey	Novartis Investigative Site	Trabzon
United Kingdom	Novartis Investigative Site	Bristol
United Kingdom	Novartis Investigative Site	Glasgow
United Kingdom	Novartis Investigative Site	Headington	Oxfordshire
United Kingdom	Novartis Investigative Site	Leeds
United Kingdom	Novartis Investigative Site	Leicester
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	London
United Kingdom	Novartis Investigative Site	Newcastle Upon Tyne
United Kingdom	Novartis Investigative Site	Salford	Manchester
United Kingdom	Novartis Investigative Site	Sheffield	South Yorkshire
United States	Novartis Investigative Site	Akron	Ohio
United States	Novartis Investigative Site	Albuquerque	New Mexico
United States	Novartis Investigative Site	Ann Arbor	Michigan
United States	Novartis Investigative Site	Aurora	Colorado
United States	Novartis Investigative Site	Baltimore	Maryland
United States	Novartis Investigative Site	Basalt	Colorado
United States	Novartis Investigative Site	Berkeley	California
United States	Novartis Investigative Site	Boulder	Colorado
United States	Novartis Investigative Site	Burlington	Vermont
United States	Novartis Investigative Site	Charlotte	North Carolina
United States	Novartis Investigative Site	Chicago	Illinois
United States	Novartis Investigative Site	Colorado Springs	Colorado
United States	Novartis Investigative Site	Dallas	Texas
United States	Novartis Investigative Site	Dayton	Ohio
United States	Novartis Investigative Site	Delray Beach	Florida
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Detroit	Michigan
United States	Novartis Investigative Site	Englewood	Colorado
United States	Novartis Investigative Site	Evanston	Illinois
United States	Novartis Investigative Site	Fairfield	Connecticut
United States	Novartis Investigative Site	Flossmoor	Illinois
United States	Novartis Investigative Site	Freehold	New Jersey
United States	Novartis Investigative Site	Hollywood	Florida
United States	Novartis Investigative Site	Jacksonville	Florida
United States	Novartis Investigative Site	Las Vegas	Nevada
United States	Novartis Investigative Site	Lebanon	New Hampshire
United States	Novartis Investigative Site	Lenexa	Kansas
United States	Novartis Investigative Site	Los Angeles	California
United States	Novartis Investigative Site	Lubbock	Texas
United States	Novartis Investigative Site	Maitland	Florida
United States	Novartis Investigative Site	Milwaukee	Wisconsin
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	New York	New York
United States	Novartis Investigative Site	Oceanside	California
United States	Novartis Investigative Site	Ormond Beach	Florida
United States	Novartis Investigative Site	Patchogue	New York
United States	Novartis Investigative Site	Philadelphia	Pennsylvania
United States	Novartis Investigative Site	Phoenix	Arizona
United States	Novartis Investigative Site	Plymouth	Minnesota
United States	Novartis Investigative Site	Port Charlotte	Florida
United States	Novartis Investigative Site	Portland	Oregon
United States	Novartis Investigative Site	Providence	Rhode Island
United States	Novartis Investigative Site	Sacramento	California
United States	Novartis Investigative Site	Saint Louis	Missouri
United States	Novartis Investigative Site	San Antonio	Texas
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Seattle	Washington
United States	Novartis Investigative Site	Springfield	Oregon
United States	Novartis Investigative Site	Stony Brook	New York
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Tampa	Florida
United States	Novartis Investigative Site	Vero Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Pharmaceuticals

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belgium,  Bulgaria,  Canada,  China,  Czechia,  Estonia,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Japan,  Latvia,  Lithuania,  Netherlands,  Poland,  Portugal,  Romania,  Russian Federation,  Slovakia,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)	The EDSS uses an ordinal scale to assess neurologic impairment in MS based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS). 3-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 3 months.	Baseline, every 3 month up to the maximum of approximately 3 years
Secondary	Percentage of Participants With 3-month Confirmed Worsening in T25W of at Least 20% From Baseline	The Timed 25-Foot Walk Test (T25W) measured the time, in seconds, to walk 25 feet (7.62 meters).; A 3-month confirmed worsening of at least 20% from baseline in the T25W was defined as an increase from baseline sustained for at least 3 months.; This outcome measure was analyzed using a Cox proportional hazards model.	Baseline, every 3 months up to the maximum of approximately 3 years
Secondary	Change From Baseline in T2 Lesion Volume	Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the total volume of T2 lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center.; The change from baseline in T2 lesion volume was analyzed using a mixed model for repeated measures (MMRM) with visit as a categorical factor and an unstructured covariance matrix and with adjustment for baseline covariates.	Baseline, Month 12 and Month 24
Secondary	Percentage of Participants With 6-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS)	The EDSS uses an ordinal scale to assess neurologic impairment in multiple sclerosis (MS) based on a neurological examination. Scores in each of 7 functional systems (Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel & Bladder, and Cerebral) and an ambulation score were combined to determine the EDSS steps, ranging from 0 (normal) to 10 (death due to MS).; 6-month confirmed disability progression is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5 sustained for at least 6 months.; This outcome measure was analyzed using a Cox proportional hazards model.	Baseline, every 3 months up to the maximum of approximately 3 years
Secondary	Annualized Relapse Rate (ARR) for Confirmed Relapses	Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (<37.5°C) or known infection.; A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater.; ARR was defined as the average number of confirmed relapses per year. ARR was analyzed using a negative binomial regression model.	Up to maximum approximately 3 years
Secondary	Percentage of Participants With First Relapse Events as Measured by Time to First Confirmed Relapse	Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (<37.5°C) or known infection.; A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater.; Time to first relapse was defined as the time from Day 1 until the start of relapse symptoms. Patients without relapse were censored at the latest known date to be at risk.; This outcome measure was analyzed using a Cox proportional hazards model.	Up to maximum approximately 3 years
Secondary	Percentage of Patients With Relapse (Confirmed Relapse and Any Relapse)	Multiple sclerosis (MS) relapse was defined as appearance of a new neurological abnormality or worsening of previously stable or improving pre-existing neurological abnormality, separated by at least 30 days from onset of a preceding clinical demyelinating event. Additionally, the abnormality had to be present for at least 24 hours and occur in the absence of fever (<37.5°C) or known infection.; A confirmed MS relapse was defined as accompanied by a clinically-relevant change in the EDSS, as defined in the study protocol, performed by the Independent EDSS Rater.	Up to maximum approximately 3 years
Secondary	Change From Baseline in MSWS-12 Converted Score	The Multiple Sclerosis Walking Scale (MSWS-12) version 2 is a patient-rated measure of walking consisting of 12 items. Walking limitations were reported by the patients using categories, generating a total transformed score ranging from 0-100. Higher scores reflected greater impairment.; The change from baseline in MSWS-12 converted score was analyzed using a repeated measures model.	Baseline, Month 12 and Month 24
Secondary	Number of T1 Gd-enhancing Lesions Per Patient Per Scan	Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the number of T1 gadolinium (Gd)-enhancing lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center.; The number of T1 Gd-enhancing lesions per patient per scan was analyzed using a negative binomial regression model.	Baseline, Month 12 and Month 24
Secondary	Number of New or Enlarging T2 Lesions Per Patient Per Year	Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the number of new or enlarging T2 lesions. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center.; The number of new or enlarging T2 lesions compared to previous scan was analyzed using a repeated measures negative binomial regression model.	Baseline, Month 12 and Month 24
Secondary	Percent Brain Volume Change (PBVC) Relative to Baseline	Magnetic resonance imaging (MRI) scans of the brain were performed every 12 months. MRI evaluation during the Core Part included the percentage change in brain volume. Each MRI scan was reviewed by a local neurologist and by a central blinded MRI reading center.; PBVC relative to baseline was analyzed using a repeated measures model (for normally distributed data) with visit as a categorical factor.	Baseline, Month 12 and Month 24
Secondary	Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of SPMS Patients With/Without Superimposed Relapses	The Expanded Disability Status Scale (EDSS) assesses neurologic impairment in multiple sclerosis (MS). EDSS scale ranges from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.; The definition of 3-month confirmed disability progression (CDP) was an increase from baseline in EDSS as defined before sustained for at least 3 months.; The following secondary progressive multiple sclerosis (SPMS) groups were defined for the analysis of this endpoint: Without superimposed relapses in the 2 years prior to study start (baseline definition); With superimposed relapses in the 2 years prior to study start (baseline definition); Without superimposed relapses during the Core Part of study (post-treatment); With superimposed relapses during the Core Part of study (post-treatment) Data was analyzed using a Cox proportional hazard model	Baseline, every 3 months up to the maximum of approximately 3 years
Secondary	Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of Rapidly and Not Rapidly Evolving Patients	The Expanded Disability Status Scale (EDSS) assesses neurologic impairment in multiple sclerosis (MS). EDSS scale ranges from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.; The definition of 3-month confirmed disability progression (CDP) was an increase from baseline in EDSS as defined before sustained for at least 3 months.; Rapidly evolving patients are defined as subjects with 1.5 or greater EDSS change in the 2 years prior to or at study start and disability progression in the 2 years prior to study start was not adjudicated.; Data was analyzed using a Cox proportional hazard model.	Baseline, every 3 months up to the maximum of approximately 3 years
Secondary	Number of Participants With 3-month CDP Events as Measured by EDSS in the Subgroup of Patients With and Without Moderate/Severe Disease Course	The Expanded Disability Status Scale (EDSS) assesses neurologic impairment in multiple sclerosis (MS). EDSS scale ranges from 0 (normal) to 10 (death due to MS). Confirmed disability is defined as an increase of score of 1 point in patients with baseline score of 3.0 to 5.0 and 0.5 point increase with baseline score of 5.5 to 6.5.; The definition of 3-month confirmed disability progression (CDP) was an increase from baseline in EDSS as defined before sustained for at least 3 months.; Moderate or severe course of disease is defined as global Multiple Sclerosis Severity Score (MSSS) of 4 or more at baseline.; Data was analyzed using a Cox proportional hazard model.	Baseline, every 3 months up to the maximum of approximately 3 years