Clinical trial NCT00297232: Natalizumab (Tysabri) Re-Initiation of Dosing
Official title: An Open-Label, Multicenter, Extension Study to Evaluate the Safety and Tolerability of Natalizumab Following Re-Initiation of Dosing in Multiple Sclerosis Subjects Who Have Completed Study C-1801, C-1802, C-1803, or C-1808 and a Dosing Suspension Safety Evaluation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Relapsing-Remitting Multiple Sclerosis
Keywords: Multiple Sclerosis
MS
Lead sponsor: Biogen
Sponsor class: INDUSTRY
First posted: 2006-02-28
Enrollment: 1094
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Detailed description: Study 101-MS-322 (NCT00306592) was conducted to evaluate the safety of natalizumab monotherapy following re-exposure to natalizumab in former clinical trial participants in Studies C-1801 (NCT00027300), C-1802 (NCT00030966), and C-1803 (NCT00097760) and included subjects in North America. In parallel with the conduct of that study, this study (101-MS-321 \[NCT00297232\]) was initiated for participants in Europe and the rest of the world. In addition, after 48 weeks, participants from 101-MS-322 (NCT00306592) could enter study 101-MS-321 (NCT 00297232), which was considered the Long-Term Treatment Period of 101-MS-322 (NCT00306592).

The primary purpose and primary outcome for both studies are identical; therefore, the combined long-term data from both studies are presented. (Combined Week 48 data from both studies are presented in the 101-MS-322 \[NCT00306592\] record.)

Eligibility criteria: Key Inclusion Criteria

* 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).

Key Exclusion Criteria

* 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

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Primary outcomes:
measure: Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression
timeFrame: up to 480 weeks
measure: Time to 48-week Confirmed EDSS Progression
timeFrame: up to 480 weeks
measure: Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0
timeFrame: Up to 480 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Camperdown
country: Australia
facility: Research Site
city: Heidelberg
country: Australia
facility: Research Site
city: Parkville
country: Australia
facility: Research Site
city: Brugge
country: Belgium
facility: Research Site
city: Brussels
country: Belgium
facility: Research Site
city: Charleroi
country: Belgium
facility: Research Site
city: Diepenbeek
country: Belgium
facility: Research Site
city: Melsbroek
country: Belgium
facility: Research Site
city: Sijsele
country: Belgium
facility: Research Site
city: Vancouver
country: Canada
facility: Research Site
state: British Columbia
city: Halifax
country: Canada
facility: Research Site
state: Nova Scotia
city: Kingston
country: Canada
facility: Research Site
state: Ontario
city: London
country: Canada
facility: Research Site
state: Ontario
city: New York
country: Canada
facility: Research Site
state: Ontario
city: Ottawa
country: Canada
facility: Research Site
state: Ontario
city: Toronto
country: Canada
facility: Research Site
state: Ontario
city: Gatineau
country: Canada
facility: Research Site
state: Quebec
city: Greenfield Park
country: Canada
facility: Research Site
state: Quebec
city: Montreal
country: Canada
facility: Research Site
state: Quebec
city: Brno
country: Czech Republic
facility: Research Site
city: Brno
country: Czech Republic
facility: Research Site
city: Hradec Kralove
country: Czech Republic
facility: Research Site
city: Olomouc
country: Czech Republic
facility: Research Site
city: Ostrava
country: Czech Republic
facility: Research Site
city: Pardubice
country: Czech Republic
facility: Research Site
city: Plzen
country: Czech Republic
facility: Research Site
city: Praha 2
country: Czech Republic
facility: Research Site
city: Praha 5
country: Czech Republic
facility: Research Site
city: Aarhus C
country: Denmark
facility: Research Site
city: Esbjerg
country: Denmark
facility: Research Site
city: Kobenhavn
country: Denmark
facility: Research Site
city: Helsinki
country: Finland
facility: Research Site
city: Tampere
country: Finland
facility: Research Site
city: Turku
country: Finland
facility: Research Site
city: Besancon
country: France
facility: Research Site
city: Bordeaux
country: France
facility: Research Site
city: Clermont-Ferrand
country: France
facility: Research Site
city: Creteil
country: France
facility: Research Site
city: Dijon
country: France
facility: Research Site
city: Lille
country: France
facility: Research Site
city: Lyon
country: France
facility: Research Site
city: Marseille
country: France
facility: Research Site
city: Nancy
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Paris
country: France
facility: Research Site
city: Rennes
country: France
facility: Research Site
city: Strasbourg
country: France
facility: Research Site
city: Toulouse
country: France
facility: Research Site
city: Berlin
country: Germany
facility: Research Site
city: Essen
country: Germany
facility: Research Site
city: Gießen
country: Germany
facility: Research Site
city: Hannover
country: Germany
facility: Research Site
city: Hennigsdorf
country: Germany
facility: Research Site
city: München
country: Germany
facility: Research Site
city: Offenbach
country: Germany
facility: Research Site
city: Osnabrück
country: Germany
facility: Research Site
city: Regensburg
country: Germany
facility: Research Site
city: Rostock
country: Germany
facility: Research Site
city: Athens
country: Greece
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Budapest
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Debrecen
country: Hungary
facility: Research Site
city: Gyor
country: Hungary
facility: Research Site
city: Nyiregyhaza
country: Hungary
facility: Research Site
city: Szekesfehervar
country: Hungary
facility: Research Site
city: Dublin
country: Ireland
facility: Research Site
city: Jerusalem
country: Israel
facility: Research Site
city: Tel Hashomer
country: Israel
facility: Research Site
city: Bari
country: Italy
facility: Research Site
city: Genova
country: Italy
facility: Research Site
city: Milano
country: Italy
facility: Research Site
city: Roma
country: Italy
facility: Research Site
city: Amsterdam
country: Netherlands
facility: Research Site
city: Breda
country: Netherlands
facility: Research Site
city: Hertogenbosch
country: Netherlands
facility: Research Site
city: Nieuwegein
country: Netherlands
facility: Research Site
city: Nijmegen
country: Netherlands
facility: Research Site
city: Rotterdam
country: Netherlands
facility: Research Site
city: Auckland
country: New Zealand
facility: Research Site
city: Christchurch
country: New Zealand
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Białystok
country: Poland
facility: Research Site
city: Bydgoszcz
country: Poland
facility: Research Site
city: Gdańsk
country: Poland
facility: Research Site
city: Katowice
country: Poland
facility: Research Site
city: Kraków
country: Poland
facility: Research Site
city: Lodz
country: Poland
facility: Research Site
city: Lublin
country: Poland
facility: Research Site
city: Warsaw
country: Poland
facility: Research Site
city: Warszawa
country: Poland
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Barcelona
country: Spain
facility: Research Site
city: Málaga
country: Spain
facility: Research Site
city: Goteborg
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Stockholm
country: Sweden
facility: Research Site
city: Basel
country: Switzerland
facility: Research Site
city: Ankara
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Istanbul
country: Turkey
facility: Research Site
city: Essex
country: United Kingdom
facility: Research Site
city: Liverpool
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: London
country: United Kingdom
facility: Research Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: Research Site
city: Oxford
country: United Kingdom
facility: Research Site
city: Sheffield
country: United Kingdom
facility: Research Site
city: Stoke on Trent
country: United Kingdom
facility: Research Site
Study officials:
affiliation: Biogen
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.