Relapsing-Remitting Multiple SclerosisTOPNCT00493298

Tysabri Observational Program

An observational study of Relapsing-Remitting Multiple Sclerosis, run by Biogen at 419 sites in 18 countries.

Completed

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

Trial summary

The primary objective of this study is to assess the long-term safety and impact on disease activity and progression of Tysabri in participants with relapsing remitting multiple sclerosis (RRMS) in a clinical practice setting. Read more about this study

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Relapsing-Remitting Multiple Sclerosis
What is being tested?: Tysabri
How many people: 6,620 participants
Where: 419 sitesin 18 countries
Study dates: 29 Jun 2007to 1 Nov 2023
Phase: Observational
Are there results?: None posted in the registry

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 65 years
All sexes
No healthy volunteers
Adult, Older adult

Study population: Participants with RRMS who are therapy-naïve to Tysabri and who meet the criteria defined in the indication statement for prescription in the respective country.

Who may be able to join

Documented diagnosis of Relapsing Remitting Multiple Sclerosis
The decision to treat with Tysabri must precede enrollment
Patient must be a new Tysabri user, and must not have had more than 3 Tysabri infusions prior to enrollment
Must have had at least one relapse in the previous year, and must satisfy locally approved therapeutic indications for Tysabri

Who cannot join

History of Progressive Multifocal Leukoencephalopathy or other opportunistic infections, or an increased risk of opportunistic infections
History of positive anti-Tysabri antibodies
Concomitant Immunomodulatory or immunosuppressive therapy during therapy with Tysabri
Patient immunocompromised at the time of enrollment
Known active malignancy
Women must not be breast feeding or pregnant, or planning to become pregnant (must use birth control unless surgically sterile)
NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Trial locations and contacts

419 sites in 18 countries.

Country

City, postcode or hospital

419 sites in 18 countries

Germany131 sites

Research site
Abensberg, 93326
Research site
Andernach, 56626
Research Site
Arnsdorf, 01477
Research site
Asperg, 71679
Research site
Augsburg, 86156
Research site
Bad Hersfeld, 36088
Research site
Bad Honnef, 53604
Research Site
Bad Kissingen, 97688
Research site
Bad Mergentheim, 97980
Research site
Bad Reichenhall, 83435
Research site
Bamberg, 96049
Research site
Berlin, 10017
Research site
Berlin, 10437
Research site
Berlin, 10785
Research site
Berlin, 10969
Research site
Berlin, 12057
Research site
Berlin, 12099
Research site
Berlin, 12203
Research site
Berlin, 13347
Research site
Berlin, 13439
Research site
Berlin, 14163
Research site
Bielefeld, 33602
Research site
Bielefeld, 33647
Research site
Bochum, 44791
Research site
Bogen, 94327
Research site
Bonn, 53111
Research site
Bruchsal, 76646
Research site
Buchholz, 21244
Research site
Celle, 29223
Research site
Chemnitz, 09117
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Cologne, 50924
Research site
Cologne, 50996
Research site
Dillingen, 66763
Research site
Dresden, 01067
Research site
Duisburg, 47169
Research site
Düren, 52351
Research site
Düsseldorf, 40211
Research site
Düsseldorf, 40225
Research site
Eisenach, 99817
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Emden, 26721
Research site
Emmendingen, 79312
Research site
Erbach im Odenwald, 64711
Research site
Erlangen, 91054
Research site
Essen, 45122
Research site
Essen, 45138
Research site
Essen, 45257
Research site
Falkenstein, 61462
Research site
Frankfurt, 60325
Research site
Freiburg im Breisgau, 79106
Research site
Görlitz, 02828
Research site
Göttingen, 37073
Research site
Greifswald, 17489
Research site
Halle, 06120
Research site
Hamburg, 20249
Research site
Hamburg, 20354
Research site
Hamburg, 22179
Research site
Heidelberg, 69120
Research site
Herford, 32052
Research site
Itzehoe, 25524
Research site
Jena, 07740
Research site
Kaiserslautern, 67655
Research site
Kaltenkirchen, 24568
Research site
Kandel, 76870
Research site
Kassel, 34121
Research site
Kastellaun, 56288
Research site
Kirchberg, 08107
Research site
Kirchheim unter Teck, 73230
Research Site
Kreuzau, 52372
Research site
Ladenburg, 68526
Research site
Leipzig, 041579
Research site
Leipzig, 04275
Research site
Lengerich, 49525
Research site
Lüdenscheid, 58511
Research site
Lüdenscheid, 58515
Research site
Ludwigshafen, 67059
Research site
Lüneburg, 21335
Research site
Magdeburg, 39120
Research site
Mannheim, 68158
Research site
Mannheim, 68161
Research site
Marburg, 35043
Research site
München, 80331
Research site
München, 80333
Research site
München, 81479
Research site
München, 81675
Research site
München, 81825
Research site
Münster, 48149
Research site
Neuburg am Inn, 86633
Research site
Neukirchen-Vluyn, 47506
Research site
Neuruppin, 16816
Research site
Nuremberg, 90419
Research site
Nuremberg, 90451
Research site
Nuremberg, 90461
Research site
Oldenburg, 26121
Research site
Oldenburg, 26127
Research site
Olpe, 57462
Research site
Osnabrück, 49074
Research site
Osnabrück, 49076
Research site
Osnabrück, 49078
Research site
Paderborn, 33098
Research site
Potsdam, 14471
Research site
Regensburg, 93053
Research site
Remscheid, 42853
Research site
Rüdersdorf, 15562
Research Site
Rülzheim, 76761
Research site
Schlüchtern, 36381
Research site
Schorndorf, 73614
Research site
Schwaebisch, 74523
Research site
Siegen, 57076
Research site
Sinsheim, 74889
Research site
Stade, 21682
Research site
Stadtroda, 07646
Research site
Stuttgart, 70176
Research site
Stuttgart, 70182
Research site
Tegel, 13507
Research site
Teupitz, 15755
Research site
Trier, 54282
Research site
Troisdorf, 53844
Research site
Ulm, 89073
Research site
Ulm, 89077
Research site
Ulm, 89081
Research site
Unterhaching, 82008
Research site
Wasserburg, 83512
Research site
Weimar, 99425
Research site
Weinheim, 69469
Research site
Wermsdorf, 04779
Research site
Wernigerode, 38855
Research site
Wiesbaden, 65185
Research site
Wolfenbüttel, 38300
Research site
Wolfratshausen, 82515
Research site
Würzburg, 97080
Research site
Zwickau, 08058

Other trials in Germany

France63 sites

Research site
Agen, 47923
Research site
Aix-en-Provence, 13100
Research site
Alençon, 61014
Research site
Angoulême, 16000
Research site ,1 Allée du Château- Dr Wagner
Ars-Laquenexy, 57245
Research site
Auxerre, 89011
Research site
Avranches, 50300
Research site
Bayonne, 64100
Research site
Beauvais, 60000
Research site
Belfort, 90000
Research site
Béthune, 62408
Research site
Beuvry, 62660
Research site
Boulogne-sur-Mer, 62321
Research site
Calais, 62107
Research site
Castelnau-le-Lez, 34171
Research site
Castres, 81108
Research site
Chambéry, 73000
Research site
Chambéry, 73011
Research site
Colmar, 68024
Research site
Compiègne, 60321
Research site
Dieppe, 76200
Research site
Dreux, 28107
Research site
Dunkirk, 59385
Research site
Épinal, 88021
Research site
Évreux, 27015
Research site
Haguenau, 67501
Research site
La Rochelle, 17000
Research site 177, rue de Versailles- Dr Servan
Le Chesnay, 78157
Research site
Le Chesnay, 78157
Research site
Le Coudray, 28630
Research site
Le Havre, 76600
Research site
Le Mans, 72037
Research site
Lille, 59000
Research site
Lisieux, 14100
Research site
Lomme, 59462
Research site
Mantes-la-Jolie, 78201
Research site
Maubeuge, 59600
Research site
Metz, 57038
Research site
Metz-Tessy, 74370
Research site
Mont-de-Marsan, 40024
Research site
Montauban, 82000
Research site
Montluçon, 03100
Research site
Montpellier, 34080
Research site
Montpellier, 34264
Research site
Mulhouse, 68100
Research site
Nice, 06105
Research site
Paris, 75020
Research site
Paris, 75674
Research site
Pau, 64000
Research site
Quimper, 29000
Research site
Reims, 51100
Research site
Saint-Aubin-sur-Scie, 76550
Research site
Sarreguemines, 57200
Research site
Saumur, 49400
Research site
St-Malo, 35400
Research site
Talant, 21240
Research site
Tarbes, 65013
Research site
Tourcoing, 59200
Research site
Trappes, 78190
Research site
Trélazé, 49800
Research site
Valenciennes, 59322
Research site
Vesoul, 70014
Research site
Vichy, 3201

Other trials in France

Belgium30 sites

Research site
Aalst, 9300
Research site
Anderlecht, 1070
Research site
Antwerp, 2020
Research site
Bocholt, 3950
Research site
Brasschaat, 2930
Research site
Bruges, 8000
Research site
Brussels, 1000
Research site
Brussels, 1180
Research site
Charleroi, 6000
Research Site
Charleroi, B-6042
Research site
Edegem, 2650
Research site
Fraiture, 4557
Research site
Genk, 3600
Research site
Ghent, 9000
Research site
Hasselt, 3500
Research site
Jette, 1090
Research site
Kortrijk, 8500
Research site
La Louvière, 7100
Research site
Leuven, 3000
Research site
Libramont, 6800
Research site
Liège, 4000
Research site
Malmedy, 4960
Research site
Melsbroek, 1820
Research site
Ostend, 8400
Research site
Ottignies, 1340
Research Site
Overpelt, 3900
Research site
Sijsele, 8340
Research site
Tournai, 7500
Research site
Wilrijk, 2610
Research site
Woluwe-Saint-Lambert, 1200

Other trials in Belgium

Netherlands24 sites

Research site
's-Hertogenbosch, 5223 GZ
Research Site
Almelo, 7600 SZ
Research site
Blaricum, 1261 AN
Research site
Breda, 4818 CK
Research site
Eindhoven, 5602 ZA
Research site
Geldrop, 5664 EH
Research site
Gouda, 2803 HH
Research site
Heerenveen, 8441 PW
Research site
Heerlen, 6419 PC
Research site
Helmond, 5700 AB
Research site
Hengelo, 7550 AM
Research site
Hoorn, 1624 NP
Research site
Leeuwarden, 8934 AD
Research Site
Meppel, 7943 SM
Research site
Nieuwegein, 3430 EM
Research site
Nijmegen, 6500 GS
Research site
Roermond, 6043 CV
Research site
Rotterdam, 3079 DZ
Research site
Sittard-Geleen, 6162 BG
Research site
The Hague, 2566 MJ
Research site
Tilburg, 5022 GC
Research site
Venray, 5801 CE
Research site
Woerden, 3447 GN
Research Site
Zwolle, 8011 JW

Other trials in Netherlands

Canada19 sites

Research site
Bracebridge, Ontario, P1L 1R1
Research site
Burnaby, British Columbia, V5G2X6
Research site
Edmonton, Alberta, T5H 4B9
Research site
Gatineau, Quebec, J8Y 1W2
Research site
Greenfield Park, Quebec, J4V 2J2
Research site
Guelph, Ontario, N1H4J4
Research site
Halifax, Nova Scotia, B3HIV7
Research site
Hamilton, Ontario, L8L5G4
Research site
Hamilton, Ontario, L8N 1T8
Research site
London, Ontario, N6A5A5
Research site
Milton, Ontario, L9T 7H3
Research site
Montreal, Quebec, H2X OA9
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Montreal, Quebec, H3A 2B4
Research site
Regina, Saskatchewan, S4S3K8
Research site
Saint John, New Brunswick, E2L 4L2
Research site
Thunder Bay, Ontario, P7B7C7
Research site
Toronto, Ontario, M5B 1W8
Research Site
Vancouver, British Columbia, V6T 2B5
Research site
Winnipeg, Manitoba, R3E0T5

Other trials in Canada

Italy17 sites

Research site
Bari, 70121
Research site
Bergamo, 24126
Research site
Cagliari, 09100
Research site
Cefalù, 90015
Research site
Chieti, 66013
Research site
Cuneo, 11100
Research site
Fidenza, 43036
Research site
Florence, 50134
Research site
Foggia, 71100
Research site
Gallarate, 21013
Research site
Milan, 20122
Research site
Milan, 20133
Research site
Naples, 80131
Research site
Orbassano, 10043
Research site
Roma, 00144
Research site
Roma, 00152
Research site
Roma, 00185

Other trials in Italy

Norway17 sites

Research site
Bergen, 5021
Research site
Bodø, 8092
Research site
Drammen, 3004
Research site
Førde, 6812
Research Site
Fredrikstad, 1603
Research site
Haugesund, 5504
Research site
Lillehammer, 2629
Research site
Lørenskog, 1478
Research site
Molde, 6407
Research site
Namsos, 7800
Research site
Oslo, 0027
Research Site
Oslo, 0407
Research Site
Skien, 3710
Research site
Stavanger, 4095
Research site
Tønsberg, 3103
Research Site
Tromsø, 9038
Research site
Trondheim, 7006

Other trials in Norway

Czechia16 sites

Research site
Brno, 62500
Research site
Brno, 65691
Research site
České Budějovice, 37087
Research site
Hradec Kralové, 50005
Research site
Jihlava, 58633
Research site
Olomouc, 77520
Research site
Ostrava, 70852
Research site
Pardubice, 53203
Research site
Pilsen, 30460
Research site
Prague, 10034
Research site
Prague, 12808
Research site
Prague, 14200
Research site
Prague, 15006
Research site
Teplice, 41528
Research Site
Teplice, 41529
Research site
Zlín, 76275

Other trials in Czechia

Mexico15 sites

Research site
Aguascalientes, 20230
Research site
Estado de México, 52763
Research Site
León, 37150
Research site
Mexico City, 01030
Research site
Mexico City, 05300
Research site
Mexico City, 06700
Research site
Mexico City, 06760
Research site
Mexico City, 09220
Research Site
Mexico City, 14260
Research site
Monterrey, Nuevo León, 64060
Research site
Monterrey, Nuevo León, 64380
Research site
Puebla City, 72540
Research Site
Puebla City, 91919
Research Site
San Luis Potosí City, 78399
Research site
Zapopan, Jalisco, 45150

Other trials in Mexico

Australia14 sites

Research site
Adelaide, South Australia, 5042
Research Site
Auchenflower, Queensland, 4066
Research site
Box Hill, Victoria, 3128
Research site
Camperdown, New South Wales, 2050
Research site
Fitzroy, Victoria, 3065
Research site
Gold Coast, Queensland, 9726
Research site
Heidelberg, Victoria, 3084
Research site
Liverpool, New South Wales, 2170
Research Site
Melbourne, Victoria, 3004
Research site
Nedlands, Western Australia, 6009
Research site
New Lambton Heights, New South Wales, 2305
Research Site
North Adelaide, South Australia, 5006
Research site
Parkville, Victoria, 3050
Research Site
St Leonards, New South Wales, 2065

Other trials in Australia

United Kingdom14 sites

Research site
Belfast, BT16 1RH
Research site
Brighton, BN2 5BE
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Bristol, BS16 1LE
Research site
Canterbury, Kent, CT1 3NG
Research site
Coventry, CV2 2DX
Research site
Edgbaston, Birmingham, B15 2TH
Research site
Exeter, EX25DW
Research site
Hammersmith, London, W6 8RF
Research site
Liverpool, L9 7LJ
Research site
Middlesbrough, TS4 3BW
Research site
Newcastle upon Tyne, NE1 4LP
Research site
Nottingham, NG7 2UH
Research site
Salford, Manchester, M6 8HD
Research site
Stoke-on-Trent, ST4 6QG

Other trials in United Kingdom

Greece13 sites

Research Site
Alexandroupoli, 68100
Research site
Athens, 10676
Research site
Athens, 11521
Research site
Athens, 11524
Research site
Athens, 11525
Research site
Athens, 11526
Research site
Heraklion, Crete, 71201
Research site
Ioannina, 45500
Research site
Pátrai, 26504
Research site
Pátrai, 26535
Research site
Thessaloniki, 54636
Research site
Thessaloniki, 56429
Research site
Thessaloniki, 57010

Other trials in Greece

Spain13 sites

Research site
Ávila, 05071
Research site
Badalona, 08916
Research site
Barcelona, 08003
Research site
Barcelona, 08907
Research site
Donostia / San Sebastian, 20014
Research site
Girona, 17007
Research site
Langreo, 33920
Research site
Logroño, 26006
Research site
Palma de Mallorca, 07014
Research site
Ponferrada, 24411
Research site
Tarragona, 43003
Research site
Tarragona, 43500
Research site
Vitoria-Gasteiz, 01009

Other trials in Spain

Portugal8 sites

Research site
Aveiro, 3810-095
Research site
Beja, 7801-849
Research site
Evora, 7000-811
Research site
Funchal, 9000
Research site
Lisbon, 1349-019
Research site
Lisbon, 1649-035
Research site
Porto, 4200 - 319
Research site
Setúbal, 2910-446

Other trials in Portugal

Argentina7 sites

Research Site
Buenos Aires, 8000
Research Site
Buenos Aires, C1061ABD
Research Site
Buenos Aires, C1118AAT
Research Site
Buenos Aires, C1428AQK
Research Site
CABA, C1015ABR
Research Site
Córdoba, X5014HYR
Research site
Santa Fe, S2000BZL

Other trials in Argentina

Finland7 sites

Research site
Helsinki, 00029
Research site
Jyväskylä, 40620
Research site
Kuopio, 70211
Research site
Pori, 28500
Research site
Seinäjoki, 60220
Research site
Tampere, 33521
Research site
Turku, 20521

Other trials in Finland

Slovakia6 sites

Research Site
Banská Bystrica, 975 17
Research Site
Bratislava, 813 69
Research Site
Bratislava, 826 06
Research site
Bratislava, 833 05
Research site
Košice, 041 66
Research site
Nitra, 949 01

Other trials in Slovakia

Brazil5 sites

Research Site
Belo Horizonte, 30130-090
Research Site
Botucatu, 18618-687
Research Site
Rio de Janeiro, 21941-590
Research Site
São Paulo, 05402-000
Research Site
São Paulo, 2151-1233

Other trials in Brazil

About this study

Official title: TOP: TYSABRI Observational Program

Read the detailed description

TOP is an epidemiological observational study of participants receiving natalizumab, with each participant to be followed for up to 15 years. This study is designed to address the long-term safety profile and the long-term impact on disease activity and progression of Tysabri with marketed use, and the impact of treatment on disability in particular by comparing the results with prospectively determined controls from established databases.

Conditions: Relapsing-Remitting Multiple Sclerosis
Being tested: Tysabri
Keywords: disease progression, Multiple Sclerosis, disease activity, Tysabri, natalizumab, long-term safety
Medical subject headings: Multiple Sclerosis, Relapsing-Remitting, Disease Progression, Multiple Sclerosis

What participants receive

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

TysabriDrug
Also called BG00002, natalizumab
According to the local prescribing information

Study groups in NCT00493298
Study group	Role	What they receive
Tysabri		According to the local prescribing information Receives: Drug: Tysabri

What is being measured

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

Number of Participants with Serious Adverse Events (SAE)
Measured: Up to 15 years

Secondary outcomes (9)

Annualized Relapse Rate (ARR)
A clinical relapse is defined as new or recurrent neurological symptoms, not associated with fever, lasting for at least 24 hours, and followed by a period of 30 days of stability or improvement. New or recurrent neurological symptoms that occur less than 30 days following the onset of a protocol-defined relapse should be considered part of the same relapse.
Measured: Yearly for up to 15 years
Distribution of the Total Number of Relapses
Measured: Yearly for up to 15 years
Time to First Relapse
Measured: Yearly for up to 15 years
Percentage of Participants with Relapse
Measured: Yearly for up to 15 years
Percentage of Participants with Disability Progression
Disability progression is defined as at least a 1.0 point increase on the Expanded Disability Status Scale (EDSS) from Baseline that is sustained over 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Measured: Yearly for up to 15 years
Percentage of Participants that reach Expanded Disability Status Score (EDSS) Milestones Indicating Increasing Disability
The percentage of participants that reach EDSS milestones such as 4.0, 6.0, and 7.0 sustained after 6 months. The EDSS measures disability status on a scale ranging from 0 to 10, with higher scores indicating more disability. Scoring is based on measures of impairment in eight functional systems on examination by a neurologist.
Measured: Yearly for up to 15 years
Percentage of Participants whose EDSS Worsened, Stabilized or Improved and Sustained over 6 Months
Measured: Yearly for up to 15 years
Evaluation of Baseline Disease Characteristics as Prognostic Indicators for Disease Activity and Disability Progression Over Time
Baseline disease characteristics evaluated will include: EDSS; Disease duration at baseline; Number of relapses during 1 and 2 years before baseline; Previous use of disease modifying therapy; Age, gender.
Measured: Yearly for up to 15 years
Evaluation of Short-Term (1 year) Disease Outcomes as Prognostic Indicators for Disease Activity and Disability Progression Over Time
Short term outcomes evaluated will include: EDSS progression during first 12 months; Occurrence of relapses during first 12 months
Measured: Yearly for up to 15 years

Timeline

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

29 Jun 20071 Nov 2023

First posted28 Jun 2007 (estimated)
Study start29 Jun 2007
Primary completion1 Nov 2023
Study completion1 Nov 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Relapsing-Remitting Multiple SclerosisStudies of the same condition, open and under way.
More trials run by BiogenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

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

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 6,620 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00493298
Sponsor's protocol ID: IMA-06-02
Acronym: TOP
Status last verified: Apr 2024
First submitted: 27 Jun 2007
Last updated: 8 Apr 2024
Results posted: No
Data monitoring committee: Yes

Publications

Butzkueven H, Kappos L, Wiendl H, Trojano M, Spelman T, Greco A, Sun Z, Lasky T; TOP Investigators. Tysabri Observational Program (TOP): long-term safety and effectiveness of natalizumab treatment in relapsing-remitting multiple sclerosis over 15 years. J Neurol Neurosurg Psychiatry. 2026 Jun 12;97(7):591-599. doi: 10.1136/jnnp-2025-337367.
PubMed 41991325
Butzkueven H, Kappos L, Spelman T, Trojano M, Wiendl H, Su R, Liao S, Hyde R, Licata S, Ho PR, Campbell N. No evidence for loss of natalizumab effectiveness with every-6-week dosing: a propensity score-matched comparison with every-4-week dosing in patients enrolled in the Tysabri Observational Program (TOP). Ther Adv Neurol Disord. 2021 Sep 27;14:17562864211042458. doi: 10.1177/17562864211042458. eCollection 2021.
PubMed 34603507
Butzkueven H, Kappos L, Wiendl H, Trojano M, Spelman T, Chang I, Kasliwal R, Jaitly S, Campbell N, Ho PR, Licata S; Tysabri Observational Program (TOP) Investigators. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020 Jun;91(6):660-668. doi: 10.1136/jnnp-2019-322326. Epub 2020 Mar 31.
PubMed 32234967
Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S; TYSABRI Observational Program (TOP) Investigators. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1190-7. doi: 10.1136/jnnp-2013-306936. Epub 2014 Feb 14.
PubMed 24532785

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Active, not recruiting
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All Relapsing-Remitting Multiple Sclerosis trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: TOP: TYSABRI Observational Program
ClinicalTrials.gov ID: NCT00493298
Acronym / sponsor ID: TOP / IMA-06-02
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: disease progression, Multiple Sclerosis, disease activity, Tysabri, natalizumab, long-term safety
Study type: Observational
Recruitment status: Completed
Enrolment: 6,620 participants (actual)
Lead sponsor: BiogenIndustry (pharma, biotech, devices)
Study start: 29 Jun 2007 (actual)
Primary completion: 1 Nov 2023 (actual)
Study completion: 1 Nov 2023 (actual)
First posted: 28 Jun 2007 (estimated)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Tysabri	–	Drug: TysabriAccording to the local prescribing information

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: Participants with RRMS who are therapy-naïve to Tysabri and who meet the criteria defined in the indication statement for prescription in the respective country.

Key inclusion criteria (4 listed)

Documented diagnosis of Relapsing Remitting Multiple Sclerosis
The decision to treat with Tysabri must precede enrollment
Patient must be a new Tysabri user, and must not have had more than 3 Tysabri infusions prior to enrollment
Must have had at least one relapse in the previous year, and must satisfy locally approved therapeutic indications for Tysabri

Key exclusion criteria (7 listed)

History of Progressive Multifocal Leukoencephalopathy or other opportunistic infections, or an increased risk of opportunistic infections
History of positive anti-Tysabri antibodies
Concomitant Immunomodulatory or immunosuppressive therapy during therapy with Tysabri
Patient immunocompromised at the time of enrollment
Known active malignancy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
TysabriAlso: BG00002, natalizumabAccording to the local prescribing information	Drug	Tysabri

Primary outcome

Number of Participants with Serious Adverse Events (SAE)
Time frame: Up to 15 years

9 secondary outcomes

Annualized Relapse Rate (ARR)
Time frame: Yearly for up to 15 years
Distribution of the Total Number of Relapses
Time frame: Yearly for up to 15 years
Time to First Relapse
Time frame: Yearly for up to 15 years
Percentage of Participants with Relapse
Time frame: Yearly for up to 15 years
Percentage of Participants with Disability Progression
Time frame: Yearly for up to 15 years
Percentage of Participants that reach Expanded Disability Status Score (EDSS) Milestones Indicating Increasing Disability
Time frame: Yearly for up to 15 years
Percentage of Participants whose EDSS Worsened, Stabilized or Improved and Sustained over 6 Months
Time frame: Yearly for up to 15 years
Evaluation of Baseline Disease Characteristics as Prognostic Indicators for Disease Activity and Disability Progression Over Time
Time frame: Yearly for up to 15 years
Evaluation of Short-Term (1 year) Disease Outcomes as Prognostic Indicators for Disease Activity and Disability Progression Over Time
Time frame: Yearly for up to 15 years

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2024.
Derived from this study: PubMed 41991325Butzkueven H, Kappos L, Wiendl H, Trojano M, Spelman T, Greco A, Sun Z, Lasky T; TOP Investigators. Tysabri Observational Program (TOP): long-term safety and effectiveness of natalizumab treatment in relapsing-remitting multiple sclerosis over 15 years. J Neurol Neurosurg Psychiatry. 2026 Jun 12;97(7):591-599. doi: 10.1136/jnnp-2025-337367.
Derived from this study: PubMed 34603507Butzkueven H, Kappos L, Spelman T, Trojano M, Wiendl H, Su R, Liao S, Hyde R, Licata S, Ho PR, Campbell N. No evidence for loss of natalizumab effectiveness with every-6-week dosing: a propensity score-matched comparison with every-4-week dosing in patients enrolled in the Tysabri Observational Program (TOP). Ther Adv Neurol Disord. 2021 Sep 27;14:17562864211042458. doi: 10.1177/17562864211042458. eCollection 2021.
Derived from this study: PubMed 32234967Butzkueven H, Kappos L, Wiendl H, Trojano M, Spelman T, Chang I, Kasliwal R, Jaitly S, Campbell N, Ho PR, Licata S; Tysabri Observational Program (TOP) Investigators. Long-term safety and effectiveness of natalizumab treatment in clinical practice: 10 years of real-world data from the Tysabri Observational Program (TOP). J Neurol Neurosurg Psychiatry. 2020 Jun;91(6):660-668. doi: 10.1136/jnnp-2019-322326. Epub 2020 Mar 31.
Derived from this study: PubMed 24532785Butzkueven H, Kappos L, Pellegrini F, Trojano M, Wiendl H, Patel RN, Zhang A, Hotermans C, Belachew S; TYSABRI Observational Program (TOP) Investigators. Efficacy and safety of natalizumab in multiple sclerosis: interim observational programme results. J Neurol Neurosurg Psychiatry. 2014 Nov;85(11):1190-7. doi: 10.1136/jnnp-2013-306936. Epub 2014 Feb 14.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Medical Director study director

Biogen

419 sites in 18 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Relapsing-Remitting Multiple Sclerosis, run by Biogen at 419 sites in 18 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 7 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 8 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 419 sites in Germany, France, Belgium, Netherlands, Canada and 13 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Number of Participants with Serious Adverse Events (SAE) (time frame: Up to 15 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 NCT00493298, which also lists 4 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 8 Apr 2024; AzTrials last refreshed its copy on 28 Oct 2026.