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

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.

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).

Study Overview

• Status: Completed
• Conditions: Secondary Progressive Multiple Sclerosis
• Intervention / Treatment: Drug: BAF312; Drug: Placebo

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 1651
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina, C1424BYD
    • Novartis Investigative Site
  • Cordoba, Argentina, X5000FAL
    • Novartis Investigative Site
  • Buenos Aires
    • Caba, Buenos Aires, Argentina, C1428AQK
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, C1181ACH
      • Novartis Investigative Site
    • Caba, Buenos Aires, Argentina, 1425
      • Novartis Investigative Site
    • Capital Federal, Buenos Aires, Argentina, 1424
      • Novartis Investigative Site
• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Novartis Investigative Site
    • Kogarah, New South Wales, Australia, 2217
      • Novartis Investigative Site
    • Liverpool, New South Wales, Australia, 2170
      • Novartis Investigative Site
  • Victoria
    • Heidelberg, Victoria, Australia, 3084
      • Novartis Investigative Site
    • Parkville, Victoria, Australia, 3050
      • Novartis Investigative Site
• Austria
  • Klagenfurt, Austria, 9020
    • Novartis Investigative Site
  • Vienna, Austria, 1090
    • Novartis Investigative Site
  • Wien, Austria, 1010
    • Novartis Investigative Site
• Belgium
  • Brugge, Belgium, 8000
    • Novartis Investigative Site
  • Bruxelles, Belgium, 1070
    • Novartis Investigative Site
  • Fraiture En Condroz, Belgium, 4557
    • Novartis Investigative Site
  • Gent, Belgium, 9000
    • Novartis Investigative Site
  • Leuven, Belgium, 3000
    • Novartis Investigative Site
  • Pelt, Belgium, 3900
    • Novartis Investigative Site
  • Sijsele, Belgium, 8340
    • Novartis Investigative Site
  • Antwerpen
    • Edegem, Antwerpen, Belgium, 2650
      • Novartis Investigative Site
• Bulgaria
  • Sofia, Bulgaria, 1113
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1413
    • Novartis Investigative Site
  • Sofia, Bulgaria, 1431
    • Novartis Investigative Site
  • Varna, Bulgaria, 9010
    • Novartis Investigative Site
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Novartis Investigative Site
    • Edmonton, Alberta, Canada, T6G 2G3
      • Novartis Investigative Site
  • British Columbia
    • Burnaby, British Columbia, Canada, V5G 2X6
      • Novartis Investigative Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 4K4
      • Novartis Investigative Site
  • Ontario
    • Kingston, Ontario, Canada, K7L 2V7
      • Novartis Investigative Site
    • Ottawa, Ontario, Canada, K1H 8L6
      • Novartis Investigative Site
    • Toronto, Ontario, Canada, M4N 3M5
      • Novartis Investigative Site
  • Quebec
    • Greenfield Park, Quebec, Canada, J4V 2J2
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H2X 0A9
      • Novartis Investigative Site
    • Montreal, Quebec, Canada, H3A 2B4
      • Novartis Investigative Site
• China
  • Beijing, China, 100730
    • Novartis Investigative Site
  • Beijing, China, 100034
    • Novartis Investigative Site
  • Beijing, China, 100028
    • Novartis Investigative Site
  • Shanghai, China, 200040
    • Novartis Investigative Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • Novartis Investigative Site
  • Shanxi
    • Taiyuan, Shanxi, China, 030001
      • Novartis Investigative Site
    • XI An, Shanxi, China, 710038
      • Novartis Investigative Site
  • Sichuan
    • Chengdu, Sichuan, China, 610041
      • Novartis Investigative Site
• Czechia
  • JIhlava, Czechia, 586 01
    • Novartis Investigative Site
  • Prague 5, Czechia, 150 00
    • Novartis Investigative Site
  • Praha, Czechia, 12808
    • Novartis Investigative Site
  • Czech Rep.
    • Brno, Czech Rep., Czechia, 625 00
      • Novartis Investigative Site
  • Czech Republic
    • Teplice, Czech Republic, Czechia, 415 01
      • Novartis Investigative Site
• Estonia
  • Tallinn, Estonia, 10617
    • Novartis Investigative Site
  • Tallinn, Estonia, 10138
    • Novartis Investigative Site
• France
  • Bordeaux Cedex, France, 33076
    • Novartis Investigative Site
  • Caen, France, 14033
    • Novartis Investigative Site
  • Lille, France, 59037
    • Novartis Investigative Site
  • Marseille Cedex 05, France, 13885
    • Novartis Investigative Site
  • Montpellier, France, 34295
    • Novartis Investigative Site
  • Nancy, France, 54035
    • Novartis Investigative Site
  • Nimes, France, 30029
    • Novartis Investigative Site
  • Paris 13, France, 75651
    • Novartis Investigative Site
  • Rennes, France, 35043
    • Novartis Investigative Site
  • St Herblain, France, 44800
    • Novartis Investigative Site
  • Strasbourg, France, 67091
    • Novartis Investigative Site
• Germany
  • Aschaffenburg, Germany, 63739
    • Novartis Investigative Site
  • Bad Mergentheim, Germany, 97980
    • Novartis Investigative Site
  • Bayreuth, Germany, 95445
    • Novartis Investigative Site
  • Berg, Germany, 82335
    • Novartis Investigative Site
  • Berlin, Germany, 10713
    • Novartis Investigative Site
  • Berlin, Germany, 13347
    • Novartis Investigative Site
  • Bielefeld, Germany, 33647
    • Novartis Investigative Site
  • Boblingen, Germany, 71032
    • Novartis Investigative Site
  • Bochum, Germany, 44791
    • Novartis Investigative Site
  • Bonn, Germany, 53111
    • Novartis Investigative Site
  • Dresden, Germany, 01307
    • Novartis Investigative Site
  • Erbach, Germany, 64711
    • Novartis Investigative Site
  • Erlangen, Germany, 91054
    • Novartis Investigative Site
  • Frankfurt, Germany, 60313
    • Novartis Investigative Site
  • Freiburg, Germany, 79106
    • Novartis Investigative Site
  • Hamburg, Germany, 22083
    • Novartis Investigative Site
  • Hamburg, Germany, 20249
    • Novartis Investigative Site
  • Hannover, Germany, 30625
    • Novartis Investigative Site
  • Hannover, Germany, 30171
    • Novartis Investigative Site
  • Heidelberg, Germany, 69120
    • Novartis Investigative Site
  • Homburg, Germany, 66421
    • Novartis Investigative Site
  • Itzehoe, Germany, 25524
    • Novartis Investigative Site
  • Jena, Germany, 07740
    • Novartis Investigative Site
  • Kassel, Germany, 34121
    • Novartis Investigative Site
  • Leipzig, Germany, 04103
    • Novartis Investigative Site
  • Leipzig, Germany, 04107
    • Novartis Investigative Site
  • Muenchen, Germany, 80377
    • Novartis Investigative Site
  • Muenster, Germany, 48149
    • Novartis Investigative Site
  • Neuburg an der Donau, Germany, 86633
    • Novartis Investigative Site
  • Oldenburg, Germany, 26122
    • Novartis Investigative Site
  • Potsdam, Germany, 14471
    • Novartis Investigative Site
  • Prien, Germany, 83209
    • Novartis Investigative Site
  • Rostock, Germany, 18057
    • Novartis Investigative Site
  • Schwendi, Germany, 88477
    • Novartis Investigative Site
  • Siegen, Germany, 57076
    • Novartis Investigative Site
  • Stade, Germany, 21682
    • Novartis Investigative Site
  • Stadtroda, Germany, 07646
    • Novartis Investigative Site
  • Teupitz, Germany, 15755
    • Novartis Investigative Site
  • Tuebingen, Germany, 72076
    • Novartis Investigative Site
  • Ulm, Germany, 89081
    • Novartis Investigative Site
  • Ulm, Germany, 89073
    • Novartis Investigative Site
  • Unterhaching, Germany, 82008
    • Novartis Investigative Site
  • Wiesbaden, Germany, 65191
    • Novartis Investigative Site
  • Wuerzburg, Germany, 97080
    • Novartis Investigative Site
  • Bavaria
    • Regensburg, Bavaria, Germany, 93053
      • Novartis Investigative Site
• Greece
  • Athens, Greece, 106 76
    • Novartis Investigative Site
  • Heraklion Crete, Greece, 711 10
    • Novartis Investigative Site
  • Thessaloniki, Greece, GR 54636
    • Novartis Investigative Site
• Hungary
  • Balassagyarmat, Hungary, 2660
    • Novartis Investigative Site
  • Budapest, Hungary, 1145
    • Novartis Investigative Site
  • Budapest, Hungary, 1085
    • Novartis Investigative Site
  • Budapest, Hungary, 1106
    • Novartis Investigative Site
  • Budapest, Hungary, 1204
    • Novartis Investigative Site
  • Eger, Hungary, H-3300
    • Novartis Investigative Site
  • Miskolc, Hungary, 3526
    • Novartis Investigative Site
  • Nyiregyhaza, Hungary, 4400
    • Novartis Investigative Site
  • Veszprem, Hungary, H 8200
    • Novartis Investigative Site
  • HUN
    • Budapest, HUN, Hungary, 1135
      • Novartis Investigative Site
    • Esztergom, HUN, Hungary, 2500
      • Novartis Investigative Site
• Ireland
  • Dublin 4, Ireland, D04 T6F
    • Novartis Investigative Site
  • Dublin 9, Ireland, D09
    • Novartis Investigative Site
• Israel
  • Jerusalem, Israel, 9112001
    • Novartis Investigative Site
  • Ramat Gan, Israel, 52621
    • Novartis Investigative Site
• Italy
  • Napoli, Italy, 80131
    • Novartis Investigative Site
  • GE
    • Genova, GE, Italy, 16132
      • Novartis Investigative Site
  • MI
    • Milano, MI, Italy, 20132
      • Novartis Investigative Site
    • Milano, MI, Italy, 20122
      • Novartis Investigative Site
  • PA
    • Cefalu, PA, Italy, 90015
      • Novartis Investigative Site
  • RM
    • Roma, RM, Italy, 00168
      • Novartis Investigative Site
    • Roma, RM, Italy, 00152
      • Novartis Investigative Site
    • Roma, RM, Italy, 00161
      • Novartis Investigative Site
    • Roma, RM, Italy, 00133
      • Novartis Investigative Site
    • Roma, RM, Italy, 00179
      • Novartis Investigative Site
• Japan
  • Aomori, Japan, 030 8553
    • Novartis Investigative Site
  • Chiba, Japan, 2608677
    • Novartis Investigative Site
  • Osaka, Japan, 556-0016
    • Novartis Investigative Site
  • Ehime
    • Toon city, Ehime, Japan, 791-0295
      • Novartis Investigative Site
  • Hokkaido
    • Asahikawa-city, Hokkaido, Japan, 070-8644
      • Novartis Investigative Site
  • Iwate
    • Morioka, Iwate, Japan, 020-8505
      • Novartis Investigative Site
  • Kyoto
    • Kyoto-city, Kyoto, Japan, 616-8147
      • Novartis Investigative Site
  • Osaka
    • Suita, Osaka, Japan, 565 0871
      • Novartis Investigative Site
  • Saitama
    • Kawagoe, Saitama, Japan, 350 8550
      • Novartis Investigative Site
    • Tokorozawa city, Saitama, Japan, 359 8513
      • Novartis Investigative Site
  • Tokyo
    • Kodaira, Tokyo, Japan, 187-8551
      • Novartis Investigative Site
    • Ota-ku, Tokyo, Japan, 145-0065
      • Novartis Investigative Site
    • Shinjuku ku, Tokyo, Japan, 162 8666
      • Novartis Investigative Site
    • Shinjuku-ku, Tokyo, Japan, 160 8582
      • Novartis Investigative Site
• Latvia
  • Riga, Latvia, LV 1002
    • Novartis Investigative Site
  • Riga, Latvia, LV-1038
    • Novartis Investigative Site
  • LV
    • Riga, LV, Latvia, LV-1005
      • Novartis Investigative Site
• Lithuania
  • Klaipeda, Lithuania, LT-92288
    • Novartis Investigative Site
  • Vilnius, Lithuania, LT-08661
    • Novartis Investigative Site
  • LTU
    • Kaunas, LTU, Lithuania, LT 50161
      • Novartis Investigative Site
• Netherlands
  • Amsterdam, Netherlands, 1105 AZ
    • Novartis Investigative Site
  • Breda, Netherlands, 4818 CK
    • Novartis Investigative Site
  • Eindhoven, Netherlands, 5623 EJ
    • Novartis Investigative Site
  • Hoorn, Netherlands, 1624 NP
    • Novartis Investigative Site
  • Sittard-Geleen, Netherlands, 6162 BG
    • Novartis Investigative Site
  • Tilburg, Netherlands, 5022 GC
    • Novartis Investigative Site
• Poland
  • Grudziadz, Poland, 86 300
    • Novartis Investigative Site
  • Katowice, Poland, 40 571
    • Novartis Investigative Site
  • Kielce, Poland, 25 726
    • Novartis Investigative Site
  • Konskie, Poland, 26 200
    • Novartis Investigative Site
  • Krakow, Poland, 31-637
    • Novartis Investigative Site
  • Lodz, Poland, 90 324
    • Novartis Investigative Site
  • Poznan, Poland, 60-355
    • Novartis Investigative Site
  • Warszawa, Poland, 02-957
    • Novartis Investigative Site
• Portugal
  • Amadora, Portugal, 2720-276
    • Novartis Investigative Site
  • Braga, Portugal, 4710243
    • Novartis Investigative Site
  • Coimbra, Portugal, 3000 075
    • Novartis Investigative Site
  • Lisboa, Portugal, 1649 035
    • Novartis Investigative Site
  • Porto, Portugal, 4099-001
    • Novartis Investigative Site
• Romania
  • Bucharest, Romania, 050098
    • Novartis Investigative Site
  • Bucharest, Romania, 020125
    • Novartis Investigative Site
  • Constanta, Romania, 900591
    • Novartis Investigative Site
  • Suceava, Romania, 727525
    • Novartis Investigative Site
  • Targu Mures, Romania, 540136
    • Novartis Investigative Site
  • Timisoara, Romania, 300736
    • Novartis Investigative Site
• Russian Federation
  • Barnaul, Russian Federation, 656024
    • Novartis Investigative Site
  • Kazan, Russian Federation, 420043
    • Novartis Investigative Site
  • Moscow, Russian Federation, 127018
    • Novartis Investigative Site
  • Moscow, Russian Federation, 119049
    • Novartis Investigative Site
  • Novosibirsk, Russian Federation, 630007
    • Novartis Investigative Site
  • Saint Petersburg, Russian Federation, 194044
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197376
    • Novartis Investigative Site
  • St. Petersburg, Russian Federation, 197110
    • Novartis Investigative Site
  • Ufa, Russian Federation, 450000
    • Novartis Investigative Site
• Slovakia
  • Banska Bystrica, Slovakia, 97517
    • Novartis Investigative Site
  • Bratislava, Slovakia, 826 06
    • Novartis Investigative Site
  • Bratislava, Slovakia, 813 69
    • Novartis Investigative Site
  • Martin, Slovakia, 036 59
    • Novartis Investigative Site
  • Nitra, Slovakia, 94911
    • Novartis Investigative Site
  • Presov, Slovakia, 081 81
    • Novartis Investigative Site
  • Trencin, Slovakia, 91171
    • Novartis Investigative Site
  • Trnava, Slovakia, 917 75
    • Novartis Investigative Site
• Spain
  • Barcelona, Spain, 08041
    • Novartis Investigative Site
  • Madrid, Spain, 28040
    • Novartis Investigative Site
  • Madrid, Spain, 28222
    • Novartis Investigative Site
  • Valencia, Spain, 46026
    • Novartis Investigative Site
  • Andalucia
    • Malaga, Andalucia, Spain, 29010
      • Novartis Investigative Site
    • Sevilla, Andalucia, Spain, 41009
      • Novartis Investigative Site
  • Barcelona
    • Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Novartis Investigative Site
  • Catalunya
    • Badalona, Catalunya, Spain, 08916
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08035
      • Novartis Investigative Site
    • Barcelona, Catalunya, Spain, 08003
      • Novartis Investigative Site
  • Comunidad Valenciana
    • Valencia, Comunidad Valenciana, Spain, 46010
      • Novartis Investigative Site
  • Murcia
    • El Palmar, Murcia, Spain, 30120
      • Novartis Investigative Site
  • Pais Vasco
    • Bilbao, Pais Vasco, Spain, 48013
      • Novartis Investigative Site
    • San Sebastian, Pais Vasco, Spain, 20080
      • Novartis Investigative Site
• Sweden
  • Goeteborg, Sweden, 413 45
    • Novartis Investigative Site
  • Stockholm, Sweden, 102 35
    • Novartis Investigative Site
  • Stockholm, Sweden, 10235
    • Novartis Investigative Site
• Switzerland
  • Basel, Switzerland, 4031
    • Novartis Investigative Site
  • Lausanne, Switzerland, 1011
    • Novartis Investigative Site
  • Lugano, Switzerland, 6900
    • Novartis Investigative Site
  • Luzern, Switzerland, 6000
    • Novartis Investigative Site
  • St Gallen, Switzerland, 9007
    • Novartis Investigative Site
  • Zuerich, Switzerland, 8091
    • Novartis Investigative Site
  • CH
    • Aarau, CH, Switzerland, 5001
      • Novartis Investigative Site
• Turkey
  • Altunizade, Turkey, 34662
    • Novartis Investigative Site
  • Haseki Istanbul, Turkey, 34096
    • Novartis Investigative Site
  • Kocaeli, Turkey, 41380
    • Novartis Investigative Site
  • Mecidiyekoy Istanbul, Turkey, 34394
    • Novartis Investigative Site
  • Samsun, Turkey, 55139
    • Novartis Investigative Site
  • Trabzon, Turkey, 61080
    • Novartis Investigative Site
  • TUR
    • Istanbul, TUR, Turkey, 34098
      • Novartis Investigative Site
• United Kingdom
  • Bristol, United Kingdom, BS10 5NB
    • Novartis Investigative Site
  • Glasgow, United Kingdom, G51 4TF
    • Novartis Investigative Site
  • Leeds, United Kingdom, LS1 3EX
    • Novartis Investigative Site
  • Leicester, United Kingdom, LE5 4PW
    • Novartis Investigative Site
  • London, United Kingdom, EC1A 7BE
    • Novartis Investigative Site
  • London, United Kingdom, W8 6RF
    • Novartis Investigative Site
  • Newcastle Upon Tyne, United Kingdom, NE1 4LP
    • Novartis Investigative Site
  • Manchester
    • Salford, Manchester, United Kingdom, M6 8HD
      • Novartis Investigative Site
  • Oxfordshire
    • Headington, Oxfordshire, United Kingdom, OX3 9DU
      • Novartis Investigative Site
  • South Yorkshire
    • Sheffield, South Yorkshire, United Kingdom, S10 2JF
      • Novartis Investigative Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85032
      • Novartis Investigative Site
  • California
    • Berkeley, California, United States, 94705
      • Novartis Investigative Site
    • Los Angeles, California, United States, 90033
      • Novartis Investigative Site
    • Oceanside, California, United States, 92056
      • Novartis Investigative Site
    • Sacramento, California, United States, 95817
      • Novartis Investigative Site
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Novartis Investigative Site
    • Basalt, Colorado, United States, 81621
      • Novartis Investigative Site
    • Boulder, Colorado, United States, 80301
      • Novartis Investigative Site
    • Colorado Springs, Colorado, United States, 80907
      • Novartis Investigative Site
    • Englewood, Colorado, United States, 80113
      • Novartis Investigative Site
  • Connecticut
    • Fairfield, Connecticut, United States, 06824
      • Novartis Investigative Site
  • Florida
    • Delray Beach, Florida, United States, 33445
      • Novartis Investigative Site
    • Hollywood, Florida, United States, 33024
      • Novartis Investigative Site
    • Jacksonville, Florida, United States, 32209
      • Novartis Investigative Site
    • Maitland, Florida, United States, 32751
      • Novartis Investigative Site
    • Ormond Beach, Florida, United States, 32174
      • Novartis Investigative Site
    • Port Charlotte, Florida, United States, 33952
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33612
      • Novartis Investigative Site
    • Tampa, Florida, United States, 33609
      • Novartis Investigative Site
    • Vero Beach, Florida, United States, 32960
      • Novartis Investigative Site
  • Illinois
    • Chicago, Illinois, United States, 60612
      • Novartis Investigative Site
    • Evanston, Illinois, United States, 60201
      • Novartis Investigative Site
    • Flossmoor, Illinois, United States, 60422
      • Novartis Investigative Site
  • Kansas
    • Lenexa, Kansas, United States, 66212
      • Novartis Investigative Site
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Novartis Investigative Site
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Novartis Investigative Site
    • Detroit, Michigan, United States, 48201
      • Novartis Investigative Site
    • Detroit, Michigan, United States, 48202 2689
      • Novartis Investigative Site
  • Minnesota
    • Plymouth, Minnesota, United States, 55446
      • Novartis Investigative Site
  • Missouri
    • Saint Louis, Missouri, United States, 63131
      • Novartis Investigative Site
  • Nevada
    • Las Vegas, Nevada, United States, 89106
      • Novartis Investigative Site
  • New Hampshire
    • Lebanon, New Hampshire, United States, 03756
      • Novartis Investigative Site
  • New Jersey
    • Freehold, New Jersey, United States, 07728
      • Novartis Investigative Site
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131-0001
      • Novartis Investigative Site
  • New York
    • New York, New York, United States, 10029
      • Novartis Investigative Site
    • New York, New York, United States, 10017
      • Novartis Investigative Site
    • Patchogue, New York, United States, 11772
      • Novartis Investigative Site
    • Stony Brook, New York, United States, 11794
      • Novartis Investigative Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28207
      • Novartis Investigative Site
  • Ohio
    • Akron, Ohio, United States, 44320
      • Novartis Investigative Site
    • Dayton, Ohio, United States, 45408
      • Novartis Investigative Site
  • Oregon
    • Portland, Oregon, United States, 97225
      • Novartis Investigative Site
    • Springfield, Oregon, United States, 97477
      • Novartis Investigative Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Novartis Investigative Site
  • Rhode Island
    • Providence, Rhode Island, United States, 02905
      • Novartis Investigative Site
  • Texas
    • Dallas, Texas, United States, 75216
      • Novartis Investigative Site
    • Lubbock, Texas, United States, 79410
      • Novartis Investigative Site
    • San Antonio, Texas, United States, 78258
      • Novartis Investigative Site
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Novartis Investigative Site
  • Washington
    • Seattle, Washington, United States, 98122
      • Novartis Investigative Site
    • Seattle, Washington, United States, 98101
      • Novartis Investigative Site
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53215
      • Novartis Investigative Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Siponimod (BAF312); Participants started on Day 1 and were uptitrated from 0.25 mg to 2 mg of BAF312 orally over a period of 6 days. After Day 7, participants continued on the treatment epoch for 3 months. During the Core Part of the study, participants participated in a maximum of 3 epochs. Following the Core Part, eligible patients enter the Extension Part during which all receive open-label BAF312.	Drug: BAF312; 0.25, 0.5, 1, and 2 mg film-coated tablets
Placebo Comparator: Placebo; Matching placebo to BAF312 was administered orally during the Core Part of the trial. Following the Core Part, eligible participants enter the Extension Part during which all receive open-label BAF312.	Drug: Placebo; Film-coated tablets

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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
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
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
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
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
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
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
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

Collaborators and Investigators

• Sponsor: Novartis Pharmaceuticals
• Investigators: Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals

Publications and helpful links

General Publications

• Gold R, Piani-Meier D, Kappos L, Bar-Or A, Vermersch P, Giovannoni G, Fox RJ, Arnold DL, Benedict RHB, Penner IK, Rouyrre N, Kilaru A, Karlsson G, Ritter S, Dahlke F, Hach T, Cree BAC. Siponimod vs placebo in active secondary progressive multiple sclerosis: a post hoc analysis from the phase 3 EXPAND study. J Neurol. 2022 Sep;269(9):5093-5104. doi: 10.1007/s00415-022-11166-z. Epub 2022 May 31.
• Cree BA, Arnold DL, Fox RJ, Gold R, Vermersch P, Benedict RH, Bar-Or A, Piani-Meier D, Rouyrre N, Ritter S, Kilaru A, Karlsson G, Giovannoni G, Kappos L. Long-term efficacy and safety of siponimod in patients with secondary progressive multiple sclerosis: Analysis of EXPAND core and extension data up to >5 years. Mult Scler. 2022 Sep;28(10):1591-1605. doi: 10.1177/13524585221083194. Epub 2022 Apr 5.
• Leppert D, Kropshofer H, Haring DA, Dahlke F, Patil A, Meinert R, Tomic D, Kappos L, Kuhle J. Blood Neurofilament Light in Progressive Multiple Sclerosis: Post Hoc Analysis of 2 Randomized Controlled Trials. Neurology. 2022 May 24;98(21):e2120-e2131. doi: 10.1212/WNL.0000000000200258. Epub 2022 Apr 4.
• Arnold DL, Piani-Meier D, Bar-Or A, Benedict RH, Cree BA, Giovannoni G, Gold R, Vermersch P, Arnould S, Dahlke F, Hach T, Ritter S, Karlsson G, Kappos L, Fox RJ; EXPAND Clinical Investigators. Effect of siponimod on magnetic resonance imaging measures of neurodegeneration and myelination in secondary progressive multiple sclerosis: Gray matter atrophy and magnetization transfer ratio analyses from the EXPAND phase 3 trial. Mult Scler. 2022 Sep;28(10):1526-1540. doi: 10.1177/13524585221076717. Epub 2022 Mar 9.
• Schur N, Gudala K, Vudumula U, Vadapalle S, Bhadhuri A, Casanova A, Adlard N, Schwenkglenks M. Cost Effectiveness and Budget Impact of Siponimod Compared to Interferon Beta-1a in the Treatment of Adult Patients with Secondary Progressive Multiple Sclerosis with Active Disease in Switzerland. Pharmacoeconomics. 2021 May;39(5):563-577. doi: 10.1007/s40273-021-01023-8. Epub 2021 Apr 1.
• Benedict RHB, Tomic D, Cree BA, Fox R, Giovannoni G, Bar-Or A, Gold R, Vermersch P, Pohlmann H, Wright I, Karlsson G, Dahlke F, Wolf C, Kappos L. Siponimod and Cognition in Secondary Progressive Multiple Sclerosis: EXPAND Secondary Analyses. Neurology. 2021 Jan 19;96(3):e376-e386. doi: 10.1212/WNL.0000000000011275. Epub 2020 Dec 16.
• Kappos L, Bar-Or A, Cree BAC, Fox RJ, Giovannoni G, Gold R, Vermersch P, Arnold DL, Arnould S, Scherz T, Wolf C, Wallstrom E, Dahlke F; EXPAND Clinical Investigators. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study. Lancet. 2018 Mar 31;391(10127):1263-1273. doi: 10.1016/S0140-6736(18)30475-6. Epub 2018 Mar 23. Erratum In: Lancet. 2018 Nov 17;392(10160):2170.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2012
• Primary Completion (Actual): April 29, 2016
• Study Completion (Actual): March 31, 2023

Study Registration Dates

• First Submitted: August 3, 2012
• First Submitted That Met QC Criteria: August 14, 2012
• First Posted (Estimated): August 15, 2012

Study Record Updates

• Last Update Posted (Actual): June 5, 2024
• Last Update Submitted That Met QC Criteria: May 7, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Secondary Progressive Multiple Sclerosis
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Neoplastic Processes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Neoplasm Metastasis; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Immunosuppressive Agents; Immunologic Factors; Sphingosine 1 Phosphate Receptor Modulators; Siponimod
• Other Study ID Numbers: CBAF312A2304; 2012-003056-36 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

IPD Plan Description

Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

Locations: central Contact Info Novartis.email@novartis.com