Natalizumab (Tysabri) Re-Initiation of Dosing - Full Text View

Purpose

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	Intervention	Phase
Relapsing-Remitting Multiple Sclerosis	Drug: Natalizumab	Phase 3


Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: 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

Resource links provided by NLM:

Genetics Home Reference related topics: multiple sclerosis

MedlinePlus related topics: Multiple Sclerosis

Drug Information available for: Natalizumab

U.S. FDA Resources

Further study details as provided by Biogen:

Primary Outcome Measures:

Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression [ Time Frame: up to 480 weeks ] [ Designated as safety issue: No ]
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.
Time to 48-week Confirmed EDSS Progression [ Time Frame: up to 480 weeks ] [ Designated as safety issue: No ]
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.
Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0 [ Time Frame: Up to 480 weeks ] [ Designated as safety issue: No ]
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.


Enrollment:	1094
Study Start Date:	March 2006
Study Completion Date:	April 2014
Primary Completion Date:	April 2014 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Natalizumab 300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks	Drug: Natalizumab Other Name: Tysabri (BG00002)

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


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00297232

Show 112 Study Locations

Sponsors and Collaborators

Biogen

Investigators


Study Director:	Medical Director	Biogen

More Information

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. This link exits the ClinicalTrials.gov site

This link exits the ClinicalTrials.gov site

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. This link exits the ClinicalTrials.gov site

Publications:

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, 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: 10.1002/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
Study First Received:	February 27, 2006
Results First Received:	April 21, 2015
Last Updated:	June 16, 2016
Health Authority:	Belgium: Federal Agency for Medicinal Products and Health Products Denmark: Danish Medicines Agency Italy: Ethics Committee Switzerland: Swissmedic Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) Ireland: Irish Medicines Board Australia: Department of Health and Ageing Therapeutic Goods Administration Spain: Spanish Agency of Medicines New Zealand: Medsafe Czech Republic: State Institute for Drug Control Greece: National Organization of Medicines Sweden: Medical Products Agency Hungary: National Institute of Pharmacy Canada: Health Canada United Kingdom: Medicines and Healthcare Products Regulatory Agency Israel: Ethics Commission Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products Finland: Finnish Medicines Agency Turkey: Ministry of Health Germany: Paul-Ehrlich-Institut France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

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

ClinicalTrials.gov processed this record on September 23, 2016

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