Natalizumab (Tysabri) Re-Initiation of Dosing

NCT00297232 | Terminated Phase 3 Results

• 1 other identifier: 101-MS-321
• Study Type: interventional
• Target: 1,094
• Locations: 21 countries
• Sites: 112

Brief Summary

The primary objectives for the initial treatment period of this study are to further evaluate the safety of natalizumab monotherapy by evaluating the risk of hypersensitivity reactions and immunogenicity following re-exposure to natalizumab and confirming the safety of switching from interferon (IFN), glatiramer acetate, or other multiple sclerosis (MS) therapies to natalizumab. The primary objective for the long-term treatment period of this study is to evaluate the long-term impact of natalizumab monotherapy on the progression of disability measured by Expanded Disability Status Scale (EDSS) changes over time.

Conditions

Relapsing-Remitting Multiple Sclerosis

Keywords

Multiple Sclerosis; MS

Outcome Measures

Primary Outcomes (3)

• Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression

  Time to 24-week confirmed EDSS progression in participants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and \< 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 24 weeks.

  up to 480 weeks

• Time to 48-week Confirmed EDSS Progression

  Time to 48-week confirmed EDSS progression in particpants with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 48-week EDSS progression was defined as ≥ 0.5 point increase from a baseline EDSS ≥ 6.0, or ≥ 1.0 point increase from a baseline EDSS ≥ 1.0 and \< 6.0, or ≥ 1.5 point increase from a baseline EDSS of 0, all sustained for 48 weeks.

  up to 480 weeks

• Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0

  Time to 24-week confirmed EDSS improvement in subjects with at least 2 post-baseline milestone EDSS assessments. EDSS assesses disability in 8 functional systems. An overall score ranging from 0 (normal) to 10 (death due to MS) was reported. Confirmed 24-week EDSS improvement is defined as ≥ 1.0 point decrease from baseline sustained for 24 weeks.

  Up to 480 weeks

Study Arms (1)

Natalizumab

EXPERIMENTAL

300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks

Drug: Natalizumab

Interventions

Natalizumab DRUG

Also known as: Tysabri (BG00002)

Natalizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• MS subjects who completed Study C-1801 (NCT00027300), C-1802 (NCT00030966), or C-1803 (NCT00097760) and a Dosing Suspension Safety Evaluation (neurological examination or a magnetic resonance imaging scan) or participated in the IMA 04001 (STARS) Study
• Subjects who are considered by the Investigator to be free of signs and symptoms suggestive of progressive multifocal leukoencephalopathy and willing to discontinue and remain free from concomitant immunosuppressive or immunomodulatory treatment (including IFN-beta and glatiramer acetate) while being treated with natalizumab during the study.
• In addition, subjects who completed 48 weeks of treatment in Study 101-MS-322 (NCT00306592) in Canada will be allowed to enter this study at the start of the long-term treatment period (Week 52 - 480).

You may not qualify if:

• Considered by the Investigator to be immunocompromised
• History of persistent anti-natalizumab antibodies, based upon testing from prior natalizumab studies
• History of any major disease or malignancy
• Discontinued natalizumab in a previous study due to allergic reaction

Sponsors & Collaborators

• Biogen: lead

Study Sites (112)

Research Site

Camperdown, 2050, Australia

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Heidelberg, 3084, Australia

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Parkville, 3050, Australia

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Bruges, 8000, Belgium

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Brussels, 1070, Belgium

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Charleroi, 6000, Belgium

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Diepenbeek, 3590, Belgium

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Melsbroek, 1820, Belgium

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Sijsele, 8340, Belgium

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Vancouver, British Columbia, V6T 2B5, Canada

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Halifax, Nova Scotia, B3H IV7, Canada

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Kingston, Ontario, K7L 2V7, Canada

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London, Ontario, N6A5A5, Canada

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New York, Ontario, M4N 3M5, Canada

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Ottawa, Ontario, K2G6E2, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Gatineau, Quebec, J8Y 1W7, Canada

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Greenfield Park, Quebec, J4V 2H1, Canada

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Montreal, Quebec, H3A2B4, Canada

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Brno, 625 00, Czechia

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Brno, 656 91, Czechia

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Hradec Králové, 500 05, Czechia

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Olomouc, 775 20, Czechia

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Ostrava, 708 52, Czechia

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Pardubice, 532 03, Czechia

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Pilsen, 323 00, Czechia

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Prague, 12000, Czechia

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Prague, 150 06, Czechia

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Aarhus C, 8000, Denmark

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Copenhagen, 2100, Denmark

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Esbjerg, 6700, Denmark

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Helsinki, 00290, Finland

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Tampere, 33520, Finland

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Turku, 20100, Finland

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Besançon, 25030, France

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Bordeaux, 33076, France

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Clermont-Ferrand, 63003, France

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Créteil, 94101, France

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Dijon, 21033, France

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Lille, 59037, France

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Lyon, 69677, France

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Marseille, 13385, France

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Nancy, 54035, France

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Paris, 75019, France

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Paris, 75651, France

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Rennes, 35033, France

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Strasbourg, 67091, France

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Toulouse, 31059, France

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Berlin, 13347, Germany

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Essen, 45122, Germany

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Giessen, 35385, Germany

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Hanover, 30625, Germany

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Hennigsdorf, 16761, Germany

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München, 81377, Germany

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Offenbach, 63069, Germany

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Osnabrück, 49076, Germany

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Regensburg, 93053, Germany

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Rostock, 18147, Germany

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Athens, 11527, Greece

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Budapest, 1021, Hungary

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Budapest, 1115, Hungary

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Budapest, 1145, Hungary

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Budapest, 1204, Hungary

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Debrecen, 4012, Hungary

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Debrecen, 4031, Hungary

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Győr, 9000, Hungary

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Nyíregyháza, 4400, Hungary

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Székesfehérvár, 8000, Hungary

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Dublin, 4, Ireland

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Jerusalem, 91120, Israel

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Tel Litwinsky, 52621, Israel

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Bari, 70124, Italy

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Genova, 16132, Italy

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Milan, 20132, Italy

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Roma, 00185, Italy

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's-Hertogenbosch, 5211 NL, Netherlands

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Amsterdam, 1081HV, Netherlands

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Breda, 4818 CK, Netherlands

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Nieuwegein, 3435 CM, Netherlands

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Nijmegen, 6533 PA, Netherlands

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Rotterdam, 3015 GD, Netherlands

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Auckland, 1023, New Zealand

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Christchurch, 8011, New Zealand

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Bialystok, 15-402, Poland

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Bialystok, 15-420, Poland

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Bydgoszcz, 85-681, Poland

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Gdansk, 80-803, Poland

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Katowice, 40-752, Poland

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Krakow, 31-530, Poland

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Lodz, 90-153, Poland

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Lublin, 20-954, Poland

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Warsaw, 02-097, Poland

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Warsaw, 02-957, Poland

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Barcelona, 08035, Spain

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Barcelona, 08907, Spain

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Málaga, 29010, Spain

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Gothenburg, 41685, Sweden

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Stockholm, 141 86, Sweden

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Stockholm, 17176, Sweden

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Basel, 4031, Switzerland

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Ankara, 06100, Turkey (Türkiye)

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Istanbul, 34303, Turkey (Türkiye)

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Istanbul, 34390, Turkey (Türkiye)

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Essex, RM7 0AG, United Kingdom

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Liverpool, L9 7AJ, United Kingdom

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London, E1 1BB, United Kingdom

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London, SE5 9RF, United Kingdom

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London, SW17 0QT, United Kingdom

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Newcastle upon Tyne, NE14LP, United Kingdom

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Oxford, OX3 9DU, United Kingdom

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Sheffield, S10 2JF, United Kingdom

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Stoke-on-Trent, ST4 7LN, United Kingdom

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Related Publications (3)

• Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, Pace A, Cheung A, Chen LL, Berman M, Zein F, Wilson E, Yednock T, Sandrock A, Goelz SE, Subramanyam M. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010 Sep;68(3):295-303. doi: 10.1002/ana.22128.

  PMID: 20737510 RESULT

• Rudick RA, O'Connor PW, Polman CH, Goodman AD, Ray SS, Griffith NM, Jurgensen SA, Gorelik L, Forrestal F, Sandrock AW, Goelz SE. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol. 2010 Sep;68(3):304-10. doi: 10.1002/ana.22107.

  PMID: 20737514 RESULT

• O'Connor P, Goodman A, Kappos L, Lublin F, Polman C, Rudick RA, Hauswirth K, Cristiano LM, Forrestal F, Duda P. Long-term safety and effectiveness of natalizumab redosing and treatment in the STRATA MS Study. Neurology. 2014 Jul 1;83(1):78-86. doi: 10.1212/WNL.0000000000000541. Epub 2014 Jun 4.

  PMID: 24898925 RESULT

Related Links

• The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families, and healthcare providers.
• MSActiveSource.com is a resource for news, information, and disease management for all individuals touched by multiple sclerosis. This site is sponsored by Biogen Idec.

MeSH Terms

Conditions

Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis

Interventions

Natalizumab

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Limitations and Caveats

Sponsor decided to terminate the study prior to all subjects reaching Week 480 as the primary objective was deemed to have been met and only approximately 45% of the original STRATA population remained in the study at the time of study termination.

Results Point of Contact

• Title: Biogen Study Medical Director
• Organization: Biogen

clinicaltrials@biogen.com

Study Officials

• Medical Director

  Biogen

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 27, 2006
• First Posted: February 28, 2006
• Study Start: March 1, 2006
• Primary Completion: April 1, 2014
• Study Completion: April 1, 2014
• Last Updated: July 15, 2016
• Results First Posted: May 29, 2015

Record last verified: 2015-05

Locations

AU (3); BE (6); GB (9); TU (3); NL (6); NZ (2); SE (3); IE (1); FR (14); PL (10); IL (2); DK (3); FI (3); HU (9); GR (1); IT (4); CZ (9); DE (10); CH (1); CA (10); ES (3)