Natalizumab (Tysabri) Re-Initiation of Dosing

Relapsing-Remitting Multiple Sclerosis Clinical Trial

— STRATA  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00297232
• Other study ID #: 101-MS-321
• Status: Terminated
• Phase: Phase 3
• First received: February 27, 2006
• Last updated: May 8, 2015
• Start date: March 2006
• Est. completion date: April 2014

Study information

• Verified date: May 2015
• Source: Biogen
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health ProductsDenmark: Danish Medicines AgencyItaly: Ethics CommitteeSwitzerland: SwissmedicNetherlands: The Central Committee on Research Involving Human Subjects (CCMO)Ireland: Irish Medicines BoardAustralia: Department of Health and Ageing Therapeutic Goods AdministrationSpain: Spanish Agency of MedicinesNew Zealand: MedsafeCzech Republic: State Institute for Drug ControlGreece: National Organization of MedicinesSweden: Medical Products AgencyHungary: National Institute of PharmacyCanada: Health CanadaUnited Kingdom: Medicines and Healthcare Products Regulatory AgencyIsrael: Ethics CommissionPoland: Office for Registration of Medicinal Products, Medical Devices and Biocidal ProductsFinland: Finnish Medicines AgencyTurkey: Ministry of HealthGermany: Paul-Ehrlich-InstitutFrance: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial 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.

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.)

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1094
• Est. completion date: April 2014
• Est. primary completion date: December 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing-Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• Natalizumab

Locations

Country	Name	City	State
Australia	Research Site	Camperdown
Australia	Research Site	Heidelberg
Australia	Research Site	Parkville
Belgium	Research Site	Brugge
Belgium	Research Site	Brussels
Belgium	Research Site	Charleroi
Belgium	Research Site	Diepenbeek
Belgium	Research Site	Melsbroek
Belgium	Research Site	Sijsele
Canada	Research Site	Gatineau	Quebec
Canada	Research Site	Greenfield Park	Quebec
Canada	Research Site	Halifax	Nova Scotia
Canada	Research Site	Kingston	Ontario
Canada	Research Site	London	Ontario
Canada	Research Site	Montreal	Quebec
Canada	Research Site	New York	Ontario
Canada	Research Site	Ottawa	Ontario
Canada	Research Site	Toronto	Ontario
Canada	Research Site	Vancouver	British Columbia
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Brno
Czech Republic	Research Site	Hradec Kralove
Czech Republic	Research Site	Olomouc
Czech Republic	Research Site	Ostrava
Czech Republic	Research Site	Pardubice
Czech Republic	Research Site	Plzen
Czech Republic	Research Site	Praha 2
Czech Republic	Research Site	Praha 5
Denmark	Research Site	Aarhus C
Denmark	Research Site	Esbjerg
Denmark	Research Site	Kobenhavn
Finland	Research Site	Helsinki
Finland	Research Site	Tampere
Finland	Research Site	Turku
France	Research Site	Besancon
France	Research Site	Bordeaux
France	Research Site	Clermont-Ferrand
France	Research Site	Creteil
France	Research Site	Dijon
France	Research Site	Lille
France	Research Site	Lyon
France	Research Site	Marseille
France	Research Site	Nancy
France	Research Site	Paris
France	Research Site	Paris
France	Research Site	Rennes
France	Research Site	Strasbourg
France	Research Site	Toulouse
Germany	Research Site	Berlin
Germany	Research Site	Essen
Germany	Research Site	Gießen
Germany	Research Site	Hannover
Germany	Research Site	Hennigsdorf
Germany	Research Site	München
Germany	Research Site	Offenbach
Germany	Research Site	Osnabrück
Germany	Research Site	Regensburg
Germany	Research Site	Rostock
Greece	Research Site	Athens
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Budapest
Hungary	Research Site	Debrecen
Hungary	Research Site	Debrecen
Hungary	Research Site	Gyor
Hungary	Research Site	Nyiregyhaza
Hungary	Research Site	Szekesfehervar
Ireland	Research Site	Dublin
Israel	Research Site	Jerusalem
Israel	Research Site	Tel Hashomer
Italy	Research Site	Bari
Italy	Research Site	Genova
Italy	Research Site	Milano
Italy	Research Site	Roma
Netherlands	Research Site	Amsterdam
Netherlands	Research Site	Breda
Netherlands	Research Site	Hertogenbosch
Netherlands	Research Site	Nieuwegein
Netherlands	Research Site	Nijmegen
Netherlands	Research Site	Rotterdam
New Zealand	Research Site	Auckland
New Zealand	Research Site	Christchurch
Poland	Research Site	Bialystok
Poland	Research Site	Bialystok
Poland	Research Site	Bydgoszcz
Poland	Research Site	Gdansk
Poland	Research Site	Katowice
Poland	Research Site	Kraków
Poland	Research Site	Lodz
Poland	Research Site	Lublin
Poland	Research Site	Warsaw
Poland	Research Site	Warszawa
Spain	Research Site	Barcelona
Spain	Research Site	Barcelona
Spain	Research Site	Málaga
Sweden	Research Site	Goteborg
Sweden	Research Site	Stockholm
Sweden	Research Site	Stockholm
Switzerland	Research Site	Basel
Turkey	Research Site	Ankara
Turkey	Research Site	Istanbul
Turkey	Research Site	Istanbul
United Kingdom	Research Site	Essex
United Kingdom	Research Site	Liverpool
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	London
United Kingdom	Research Site	Newcastle Upon Tyne
United Kingdom	Research Site	Oxford
United Kingdom	Research Site	Sheffield
United Kingdom	Research Site	Stoke on Trent

Sponsors (1)

Lead Sponsor	Collaborator
Biogen

Countries where clinical trial is conducted

Australia,  Belgium,  Canada,  Czech Republic,  Denmark,  Finland,  France,  Germany,  Greece,  Hungary,  Ireland,  Israel,  Italy,  Netherlands,  New Zealand,  Poland,  Spain,  Sweden,  Switzerland,  Turkey,  United Kingdom, 

References & 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; — View 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: 10.121 — View Citation

Rudick RA, O'Connor PW, Polman CH, Goodman AD, Ray SS, Griffith NM, Jurgensen SA, Gorelik L, Forrestal F, Sandrock AW, E Goelz S. Assessment of JC virus DNA in blood and urine from natalizumab-treated patients. Ann Neurol. 2010 Sep;68(3):304-10. doi: 10.1 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	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	No
Primary	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	No

External Links

•   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.
•   The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families, and healthcare providers.