AzTrials
AzTrials

Secondary Progressive Multiple SclerosisPhase 3NCT01665144

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

A Phase 3 study testing BAF312 in people with Secondary Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 290 sites in 31 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

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). Read more about this study

Who is it for?
Ages 18 to 60 years
Conditions the study is for
Secondary Progressive Multiple Sclerosis
What is being tested?
BAF312
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
1,651 participants
Where
290 sitesin 31 countries
Study dates
20 Dec 2012to 31 Mar 2023
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • 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

Who cannot join

  • 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

Trial locations and contacts

290 sites in 31 countries.

290 sites in 31 countries

United States52 sites

  • Novartis Investigative Site

    Akron, Ohio, 44320

  • Novartis Investigative Site

    Albuquerque, New Mexico, 87131-0001

  • Novartis Investigative Site

    Ann Arbor, Michigan, 48109

  • Novartis Investigative Site

    Aurora, Colorado, 80045

  • Novartis Investigative Site

    Baltimore, Maryland, 21287

  • Novartis Investigative Site

    Basalt, Colorado, 81621

  • Novartis Investigative Site

    Berkeley, California, 94705

  • Novartis Investigative Site

    Boulder, Colorado, 80301

  • Novartis Investigative Site

    Burlington, Vermont, 05401

  • Novartis Investigative Site

    Charlotte, North Carolina, 28207

  • Novartis Investigative Site

    Chicago, Illinois, 60612

  • Novartis Investigative Site

    Colorado Springs, Colorado, 80907

  • Novartis Investigative Site

    Dallas, Texas, 75216

  • Novartis Investigative Site

    Dayton, Ohio, 45408

  • Novartis Investigative Site

    Delray Beach, Florida, 33445

  • Novartis Investigative Site

    Detroit, Michigan, 48201

  • Novartis Investigative Site

    Detroit, Michigan, 48202 2689

  • Novartis Investigative Site

    Englewood, Colorado, 80113

  • Novartis Investigative Site

    Evanston, Illinois, 60201

  • Novartis Investigative Site

    Fairfield, Connecticut, 06824

  • Novartis Investigative Site

    Flossmoor, Illinois, 60422

  • Novartis Investigative Site

    Freehold, New Jersey, 07728

  • Novartis Investigative Site

    Hollywood, Florida, 33024

  • Novartis Investigative Site

    Jacksonville, Florida, 32209

  • Novartis Investigative Site

    Las Vegas, Nevada, 89106

  • Novartis Investigative Site

    Lebanon, New Hampshire, 03756

  • Novartis Investigative Site

    Lenexa, Kansas, 66212

  • Novartis Investigative Site

    Los Angeles, California, 90033

  • Novartis Investigative Site

    Lubbock, Texas, 79410

  • Novartis Investigative Site

    Maitland, Florida, 32751

  • Novartis Investigative Site

    Milwaukee, Wisconsin, 53215

  • Novartis Investigative Site

    New York, New York, 10017

  • Novartis Investigative Site

    New York, New York, 10029

  • Novartis Investigative Site

    Oceanside, California, 92056

  • Novartis Investigative Site

    Ormond Beach, Florida, 32174

  • Novartis Investigative Site

    Patchogue, New York, 11772

  • Novartis Investigative Site

    Philadelphia, Pennsylvania, 19104

  • Novartis Investigative Site

    Phoenix, Arizona, 85032

  • Novartis Investigative Site

    Plymouth, Minnesota, 55446

  • Novartis Investigative Site

    Port Charlotte, Florida, 33952

  • Novartis Investigative Site

    Portland, Oregon, 97225

  • Novartis Investigative Site

    Providence, Rhode Island, 02905

  • Novartis Investigative Site

    Sacramento, California, 95817

  • Novartis Investigative Site

    San Antonio, Texas, 78258

  • Novartis Investigative Site

    Seattle, Washington, 98101

  • Novartis Investigative Site

    Seattle, Washington, 98122

  • Novartis Investigative Site

    Springfield, Oregon, 97477

  • Novartis Investigative Site

    St Louis, Missouri, 63131

  • Novartis Investigative Site

    Stony Brook, New York, 11794

  • Novartis Investigative Site

    Tampa, Florida, 33609

  • Novartis Investigative Site

    Tampa, Florida, 33612

  • Novartis Investigative Site

    Vero Beach, Florida, 32960

Other trials in United States

Germany45 sites

  • Novartis Investigative Site

    Aschaffenburg, 63739

  • Novartis Investigative Site

    Bad Mergentheim, 97980

  • Novartis Investigative Site

    Bayreuth, 95445

  • Novartis Investigative Site

    Berg, 82335

  • Novartis Investigative Site

    Berlin, 10713

  • Novartis Investigative Site

    Berlin, 13347

  • Novartis Investigative Site

    Bielefeld, 33647

  • Novartis Investigative Site

    Böblingen, 71032

  • Novartis Investigative Site

    Bochum, 44791

  • Novartis Investigative Site

    Bonn, 53111

  • Novartis Investigative Site

    Dresden, 01307

  • Novartis Investigative Site

    Erbach im Odenwald, 64711

  • Novartis Investigative Site

    Erlangen, 91054

  • Novartis Investigative Site

    Frankfurt, 60313

  • Novartis Investigative Site

    Freiburg im Breisgau, 79106

  • Novartis Investigative Site

    Hamburg, 20249

  • Novartis Investigative Site

    Hamburg, 22083

  • Novartis Investigative Site

    Hanover, 30171

  • Novartis Investigative Site

    Hanover, 30625

  • Novartis Investigative Site

    Heidelberg, 69120

  • Novartis Investigative Site

    Homburg, 66421

  • Novartis Investigative Site

    Itzehoe, 25524

  • Novartis Investigative Site

    Jena, 07740

  • Novartis Investigative Site

    Kassel, 34121

  • Novartis Investigative Site

    Leipzig, 04103

  • Novartis Investigative Site

    Leipzig, 04107

  • Novartis Investigative Site

    München, 80377

  • Novartis Investigative Site

    Münster, 48149

  • Novartis Investigative Site

    Neuburg an der Donau, 86633

  • Novartis Investigative Site

    Oldenburg, 26122

  • Novartis Investigative Site

    Potsdam, 14471

  • Novartis Investigative Site

    Prien am Chiemsee, 83209

  • Novartis Investigative Site

    Regensburg, Bavaria, 93053

  • Novartis Investigative Site

    Rostock, 18057

  • Novartis Investigative Site

    Schwendi, 88477

  • Novartis Investigative Site

    Siegen, 57076

  • Novartis Investigative Site

    Stade, 21682

  • Novartis Investigative Site

    Stadtroda, 07646

  • Novartis Investigative Site

    Teupitz, 15755

  • Novartis Investigative Site

    Tübingen, 72076

  • Novartis Investigative Site

    Ulm, 89073

  • Novartis Investigative Site

    Ulm, 89081

  • Novartis Investigative Site

    Unterhaching, 82008

  • Novartis Investigative Site

    Wiesbaden, 65191

  • Novartis Investigative Site

    Würzburg, 97080

Other trials in Germany

Japan14 sites

  • Novartis Investigative Site

    Aomori, 030 8553

  • Novartis Investigative Site

    Asahikawa, Hokkaido, 070-8644

  • Novartis Investigative Site

    Chiba, 2608677

  • Novartis Investigative Site

    Kawagoe, Saitama, 350 8550

  • Novartis Investigative Site

    Kodaira, Tokyo, 187-8551

  • Novartis Investigative Site

    Kyoto, Kyoto, 616-8147

  • Novartis Investigative Site

    Morioka, Iwate, 020-8505

  • Novartis Investigative Site

    Osaka, 556-0016

  • Novartis Investigative Site

    Ōta-ku, Tokyo, 145-0065

  • Novartis Investigative Site

    Shinjuku Ku, Tokyo, 162 8666

  • Novartis Investigative Site

    Shinjuku-ku, Tokyo, 160 8582

  • Novartis Investigative Site

    Suita, Osaka, 565 0871

  • Novartis Investigative Site

    Tokorozawa, Saitama, 359 8513

  • Novartis Investigative Site

    Tōon, Ehime, 791-0295

Other trials in Japan

Spain14 sites

  • Novartis Investigative Site

    Badalona, Catalonia, 08916

  • Novartis Investigative Site

    Barcelona, Catalonia, 08003

  • Novartis Investigative Site

    Barcelona, Catalonia, 08035

  • Novartis Investigative Site

    Barcelona, 08041

  • Novartis Investigative Site

    Bilbao, Basque Country, 48013

  • Novartis Investigative Site

    Donostia / San Sebastian, Basque Country, 20080

  • Novartis Investigative Site

    El Palmar, Murcia, 30120

  • Novartis Investigative Site

    L'Hospitalet de Llobregat, Barcelona, 08907

  • Novartis Investigative Site

    Madrid, 28040

  • Novartis Investigative Site

    Madrid, 28222

  • Novartis Investigative Site

    Málaga, Andalusia, 29010

  • Novartis Investigative Site

    Seville, Andalusia, 41009

  • Novartis Investigative Site

    Valencia, Valencia, 46010

  • Novartis Investigative Site

    Valencia, 46026

Other trials in Spain

France11 sites

  • Novartis Investigative Site

    Bordeaux, 33076

  • Novartis Investigative Site

    Caen, 14033

  • Novartis Investigative Site

    Lille, 59037

  • Novartis Investigative Site

    Marseille, 13885

  • Novartis Investigative Site

    Montpellier, 34295

  • Novartis Investigative Site

    Nancy, 54035

  • Novartis Investigative Site

    Nîmes, 30029

  • Novartis Investigative Site

    Paris, 75651

  • Novartis Investigative Site

    Rennes, 35043

  • Novartis Investigative Site

    Saint-Herblain, 44800

  • Novartis Investigative Site

    Strasbourg, 67091

Other trials in France

Hungary11 sites

  • Novartis Investigative Site

    Balassagyarmat, 2660

  • Novartis Investigative Site

    Budapest, HUN, 1135

  • Novartis Investigative Site

    Budapest, 1085

  • Novartis Investigative Site

    Budapest, 1106

  • Novartis Investigative Site

    Budapest, 1145

  • Novartis Investigative Site

    Budapest, 1204

  • Novartis Investigative Site

    Eger, H-3300

  • Novartis Investigative Site

    Esztergom, HUN, 2500

  • Novartis Investigative Site

    Miskolc, 3526

  • Novartis Investigative Site

    Nyíregyháza, 4400

  • Novartis Investigative Site

    Veszprém, H 8200

Other trials in Hungary

Canada10 sites

  • Novartis Investigative Site

    Burnaby, British Columbia, V5G 2X6

  • Novartis Investigative Site

    Calgary, Alberta, T2N 2T9

  • Novartis Investigative Site

    Edmonton, Alberta, T6G 2G3

  • Novartis Investigative Site

    Greenfield Park, Quebec, J4V 2J2

  • Novartis Investigative Site

    Halifax, Nova Scotia, B3H 4K4

  • Novartis Investigative Site

    Kingston, Ontario, K7L 2V7

  • Novartis Investigative Site

    Montreal, Quebec, H2X 0A9

  • Novartis Investigative Site

    Montreal, Quebec, H3A 2B4

  • Novartis Investigative Site

    Ottawa, Ontario, K1H 8L6

  • Novartis Investigative Site

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Italy10 sites

  • Novartis Investigative Site

    Cefalù, PA, 90015

  • Novartis Investigative Site

    Genova, GE, 16132

  • Novartis Investigative Site

    Milan, MI, 20122

  • Novartis Investigative Site

    Milan, MI, 20132

  • Novartis Investigative Site

    Naples, 80131

  • Novartis Investigative Site

    Roma, RM, 00133

  • Novartis Investigative Site

    Roma, RM, 00152

  • Novartis Investigative Site

    Roma, RM, 00161

  • Novartis Investigative Site

    Roma, RM, 00168

  • Novartis Investigative Site

    Roma, RM, 00179

Other trials in Italy

United Kingdom10 sites

  • Novartis Investigative Site

    Bristol, BS10 5NB

  • Novartis Investigative Site

    Glasgow, G51 4TF

  • Novartis Investigative Site

    Headington, Oxfordshire, OX3 9DU

  • Novartis Investigative Site

    Leeds, LS1 3EX

  • Novartis Investigative Site

    Leicester, LE5 4PW

  • Novartis Investigative Site

    London, EC1A 7BE

  • Novartis Investigative Site

    London, W8 6RF

  • Novartis Investigative Site

    Newcastle upon Tyne, NE1 4LP

  • Novartis Investigative Site

    Salford, Manchester, M6 8HD

  • Novartis Investigative Site

    Sheffield, South Yorkshire, S10 2JF

Other trials in United Kingdom

Russia9 sites

  • Novartis Investigative Site

    Barnaul, 656024

  • Novartis Investigative Site

    Kazan', 420043

  • Novartis Investigative Site

    Moscow, 119049

  • Novartis Investigative Site

    Moscow, 127018

  • Novartis Investigative Site

    Novosibirsk, 630007

  • Novartis Investigative Site

    Saint Petersburg, 194044

  • Novartis Investigative Site

    Saint Petersburg, 197110

  • Novartis Investigative Site

    Saint Petersburg, 197376

  • Novartis Investigative Site

    Ufa, 450000

Other trials in Russia

Belgium8 sites

  • Novartis Investigative Site

    Bruges, 8000

  • Novartis Investigative Site

    Brussels, 1070

  • Novartis Investigative Site

    Edegem, Antwerpen, 2650

  • Novartis Investigative Site

    Fraiture En Condroz, Belgium, 4557

  • Novartis Investigative Site

    Ghent, 9000

  • Novartis Investigative Site

    Leuven, 3000

  • Novartis Investigative Site

    Overpelt, 3900

  • Novartis Investigative Site

    Sijsele, 8340

Other trials in Belgium

China8 sites

  • Novartis Investigative Site

    Beijing, 100028

  • Novartis Investigative Site

    Beijing, 100034

  • Novartis Investigative Site

    Beijing, 100730

  • Novartis Investigative Site

    Changchun, Jilin, 130021

  • Novartis Investigative Site

    Chengdu, Sichuan, 610041

  • Novartis Investigative Site

    Shanghai, 200040

  • Novartis Investigative Site

    Taiyuan, Shanxi, 030001

  • Novartis Investigative Site

    Xi’an, Shanxi, 710038

Other trials in China

Poland8 sites

  • Novartis Investigative Site

    Gmina Końskie, 26 200

  • Novartis Investigative Site

    Grudziądz, 86 300

  • Novartis Investigative Site

    Katowice, 40 571

  • Novartis Investigative Site

    Kielce, 25 726

  • Novartis Investigative Site

    Krakow, 31-637

  • Novartis Investigative Site

    Lodz, 90 324

  • Novartis Investigative Site

    Poznan, 60-355

  • Novartis Investigative Site

    Warsaw, 02-957

Other trials in Poland

Slovakia8 sites

  • Novartis Investigative Site

    Banská Bystrica, 97517

  • Novartis Investigative Site

    Bratislava, 813 69

  • Novartis Investigative Site

    Bratislava, 826 06

  • Novartis Investigative Site

    Martin, 036 59

  • Novartis Investigative Site

    Nitra, 94911

  • Novartis Investigative Site

    Prešov, 081 81

  • Novartis Investigative Site

    Trenčín, 91171

  • Novartis Investigative Site

    Trnava, 917 75

Other trials in Slovakia

Switzerland7 sites

  • Novartis Investigative Site

    Aarau, CH, 5001

  • Novartis Investigative Site

    Basel, 4031

  • Novartis Investigative Site

    Lausanne, 1011

  • Novartis Investigative Site

    Lucerne, 6000

  • Novartis Investigative Site

    Lugano, 6900

  • Novartis Investigative Site

    Sankt Gallen, 9007

  • Novartis Investigative Site

    Zurich, 8091

Other trials in Switzerland

Turkey (Türkiye)7 sites

  • Novartis Investigative Site

    Altunizade, 34662

  • Novartis Investigative Site

    Haseki Istanbul, 34096

  • Novartis Investigative Site

    Istanbul, TUR, 34098

  • Novartis Investigative Site

    Kocaeli, 41380

  • Novartis Investigative Site

    Mecidiyekoy Istanbul, 34394

  • Novartis Investigative Site

    Samsun, 55139

  • Novartis Investigative Site

    Trabzon, 61080

Other trials in Turkey (Türkiye)

Argentina6 sites

  • Novartis Investigative Site

    Buenos Aires, C1424BYD

  • Novartis Investigative Site

    CABA, Buenos Aires, 1425

  • Novartis Investigative Site

    CABA, Buenos Aires, C1181ACH

  • Novartis Investigative Site

    CABA, Buenos Aires, C1428AQK

  • Novartis Investigative Site

    Capital Federal, Buenos Aires, 1424

  • Novartis Investigative Site

    Córdoba, X5000FAL

Other trials in Argentina

Netherlands6 sites

  • Novartis Investigative Site

    Amsterdam, 1105 AZ

  • Novartis Investigative Site

    Breda, 4818 CK

  • Novartis Investigative Site

    Eindhoven, 5623 EJ

  • Novartis Investigative Site

    Hoorn, 1624 NP

  • Novartis Investigative Site

    Sittard-Geleen, 6162 BG

  • Novartis Investigative Site

    Tilburg, 5022 GC

Other trials in Netherlands

Romania6 sites

  • Novartis Investigative Site

    Bucharest, 020125

  • Novartis Investigative Site

    Bucharest, 050098

  • Novartis Investigative Site

    Constanța, 900591

  • Novartis Investigative Site

    Suceava, 727525

  • Novartis Investigative Site

    Târgu Mureş, 540136

  • Novartis Investigative Site

    Timișoara, 300736

Other trials in Romania

Australia5 sites

  • Novartis Investigative Site

    Camperdown, New South Wales, 2050

  • Novartis Investigative Site

    Heidelberg, Victoria, 3084

  • Novartis Investigative Site

    Kogarah, New South Wales, 2217

  • Novartis Investigative Site

    Liverpool, New South Wales, 2170

  • Novartis Investigative Site

    Parkville, Victoria, 3050

Other trials in Australia

Czechia5 sites

  • Novartis Investigative Site

    Brno, Czech Rep., 625 00

  • Novartis Investigative Site

    Jihlava, 586 01

  • Novartis Investigative Site

    Prague, 12808

  • Novartis Investigative Site

    Prague, 150 00

  • Novartis Investigative Site

    Teplice, Czech Republic, 415 01

Other trials in Czechia

Portugal5 sites

  • Novartis Investigative Site

    Amadora, 2720-276

  • Novartis Investigative Site

    Braga, 4710243

  • Novartis Investigative Site

    Coimbra, 3000 075

  • Novartis Investigative Site

    Lisbon, 1649 035

  • Novartis Investigative Site

    Porto, 4099-001

Other trials in Portugal

Bulgaria4 sites

  • Novartis Investigative Site

    Sofia, 1113

  • Novartis Investigative Site

    Sofia, 1413

  • Novartis Investigative Site

    Sofia, 1431

  • Novartis Investigative Site

    Varna, 9010

Other trials in Bulgaria

Austria3 sites

  • Novartis Investigative Site

    Klagenfurt, 9020

  • Novartis Investigative Site

    Vienna, 1010

  • Novartis Investigative Site

    Vienna, 1090

Other trials in Austria

Greece3 sites

  • Novartis Investigative Site

    Athens, 106 76

  • Novartis Investigative Site

    Heraklion Crete, 711 10

  • Novartis Investigative Site

    Thessaloniki, GR 54636

Other trials in Greece

Latvia3 sites

  • Novartis Investigative Site

    Riga, LV, LV-1005

  • Novartis Investigative Site

    Riga, LV 1002

  • Novartis Investigative Site

    Riga, LV-1038

Other trials in Latvia

Lithuania3 sites

  • Novartis Investigative Site

    Kaunas, LTU, LT 50161

  • Novartis Investigative Site

    Klaipėda, LT-92288

  • Novartis Investigative Site

    Vilnius, LT-08661

Other trials in Lithuania

Sweden3 sites

  • Novartis Investigative Site

    Gothenburg, 413 45

  • Novartis Investigative Site

    Stockholm, 102 35

  • Novartis Investigative Site

    Stockholm, 10235

Other trials in Sweden

Estonia2 sites

  • Novartis Investigative Site

    Tallinn, 10138

  • Novartis Investigative Site

    Tallinn, 10617

Other trials in Estonia

Ireland2 sites

  • Novartis Investigative Site

    Dublin, D04 T6F

  • Novartis Investigative Site

    Dublin, D09

Other trials in Ireland

Israel2 sites

  • Novartis Investigative Site

    Jerusalem, 9112001

  • Novartis Investigative Site

    Ramat Gan, 52621

Other trials in Israel

About this study

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.

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).

Read the 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.

Being tested
BAF312, Placebo
Keywords
Secondary Progressive Multiple Sclerosis
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BAF312Drug

    0.25, 0.5, 1, and 2 mg film-coated tablets

  • PlaceboDrug

    Film-coated tablets

Study groups in NCT01665144
Study groupRoleWhat they receive
Siponimod (BAF312)ExperimentalParticipants 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.
Receives: Drug: BAF312
PlaceboPlacebo comparatorMatching 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.
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, every 3 month up to the maximum of approximately 3 years

Secondary outcomes (13)

  1. 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.

    Measured: Baseline, every 3 months up to the maximum of approximately 3 years

  2. 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.

    Measured: Baseline, Month 12 and Month 24

  3. 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.

    Measured: Baseline, every 3 months up to the maximum of approximately 3 years

  4. 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.

    Measured: Up to maximum approximately 3 years

  5. 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.

    Measured: Up to maximum approximately 3 years

  6. 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.

    Measured: Up to maximum approximately 3 years

  7. 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.

    Measured: Baseline, Month 12 and Month 24

  8. 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.

    Measured: Baseline, Month 12 and Month 24

  9. 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.

    Measured: Baseline, Month 12 and Month 24

  10. 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.

    Measured: Baseline, Month 12 and Month 24

  11. 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

    Measured: Baseline, every 3 months up to the maximum of approximately 3 years

  12. 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.

    Measured: Baseline, every 3 months up to the maximum of approximately 3 years

  13. 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.

    Measured: Baseline, every 3 months up to the maximum of approximately 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 Aug 2012 (estimated)
  2. Study start20 Dec 2012
  3. Primary completion29 Apr 2016
  4. Study completion31 Mar 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
1,651 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01665144
Sponsor's protocol ID
CBAF312A2304
Other IDs
2012-003056-36
Status last verified
May 2024
First submitted
3 Aug 2012
Last updated
5 Jun 2024
Individual data sharing
Yes: 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

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.

    PubMed 35639197

  • 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.

    PubMed 35380078

  • 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.

    PubMed 35379762

  • 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.

    PubMed 35261318

  • 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.

    PubMed 33791945

  • 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.

    PubMed 33328324

  • 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.

    PubMed 29576505

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing BAF312 in people with Secondary Progressive Multiple Sclerosis, run by Novartis Pharmaceuticals at 290 sites in 31 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 290 sites in United States, Germany, Japan, Spain, France and 26 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 31 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Participants With 3-month Confirmed Disability Progression (CDP) Events as Measured by the Expanded Disability Status Scale (EDSS) (time frame: Baseline, every 3 month up to the maximum of approximately 3 years). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01665144, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jun 2024.

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