Natalizumab (Tysabri) Re-Initiation of Dosing (STRATA)

Study Description

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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.

Condition or disease	Intervention/treatment	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: Natalizumab	Phase 3

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.)

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	1094 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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 Start Date :	March 2006
Actual Primary Completion Date :	April 2014
Actual Study Completion Date :	April 2014

Arms and Interventions

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Arm	Intervention/treatment
Experimental: Natalizumab; 300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks	Drug: Natalizumab; Other Name: Tysabri (BG00002)

Outcome Measures

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Primary Outcome Measures :

1. Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: up to 480 weeks ]
   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.
2. Time to 48-week Confirmed EDSS Progression [ Time Frame: up to 480 weeks ]
   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.
3. Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0 [ Time Frame: Up to 480 weeks ]
   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.

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

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  Show 112 Study Locations

Sponsors and Collaborators

Biogen

Investigators

Study Director:	Medical Director	Biogen

More Information

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Additional Information:

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. 

Publications of Results:

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.

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.

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. Erratum in: Neurology. 2014 Aug 19;83(8):773.

Responsible Party:	Biogen
ClinicalTrials.gov Identifier:	NCT00297232 History of Changes
Other Study ID Numbers:	101-MS-321
First Posted:	February 28, 2006
Results First Posted:	May 29, 2015
Last Update Posted:	July 15, 2016
Last Verified:	May 2015

Keywords provided by Biogen:

Multiple Sclerosis; MS

Additional relevant MeSH terms:

Sclerosis; Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Pathologic Processes; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases	Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Natalizumab; Immunologic Factors; Physiological Effects of Drugs