Back to resultsNatalizumab Re-Initiation of Dosing
Primary Purpose
Multiple Sclerosis, Relapsing-Remitting
Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
BG00002 (natalizumab)
Sponsored by
About this trial
This is an interventional treatment trial for Multiple Sclerosis, Relapsing-Remitting focused on measuring Multiple Sclerosis, MS
Eligibility Criteria
Inclusion Criteria: MS subjects who completed Study C-1801 (NCT00027300), C-1802 (NCT00030966), or C-1803 (NCT00097760) and completed a Dosing Suspension Safety Evaluation (neurological examination and magnetic resonance imaging [MRI] scan) Considered by the investigator to be free of signs and symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety Evaluation from Study C-1808 [NCT000276172] may be used) Other protocol-defined inclusion criteria may apply Exclusion Criteria: Considered by the investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety Evaluation from Study C-1808 may be used), or due to prior immunosuppressive treatment History of persistent anti-natalizumab antibodies, based upon testing from prior natalizumab studies Other protocol-defined exclusion criteria may apply
Sites / Locations
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Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Natalizumab
Arm Description
All study participants in 101-MS-322 (NCT00306592) and 101-MS-321 (NCT00297232) received open label 300 mg intravenous (IV) natalizumab 60-minute infusion once every 4 weeks (28 days ±7 days) for up to 48 weeks. After 48 weeks, participants from 101-MS-322 (NCT00306592) entering study 101-MS-321 (NCT 00297232; considered the Long-Term Treatment Period of 101-MS-322) were continued on treatment from Week 52 through Week 480.
Outcomes
Primary Outcome Measures
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious AEs (SAEs)
AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Treatment-emergent AEs: events in participants who had received at least 1 dose of study drug, regardless of relationship to study drug.
Number of Participants With Hypersensitivity-related Adverse Events
For purposes of this analysis, the terms 'hypersensitivity' and 'drug hypersensitivity' were categorized by their temporal relationship to study drug infusion (within 2 hours of the start of the infusion), and were considered equivalent. Hypersensitivity reactions are defined as infusion reactions with the following preferred terms: hypersensitivity not otherwise specified (NOS), anaphylactic reaction, anaphylactoid reaction, dermatitis allergic, drug hypersensitivity, urticaria NOS, vasoconstriction, urticaria generalised, hypersensitivity, urticaria.
Number of Participants With Antibodies to Natalizumab
'Positive with unknown persistence' is defined as a positive result (≥0.5 micrograms/mL) at one timepoint only with no confirmatory re-test available at least 42 days later. 'Transient positive' is defined as a positive at one timepoint but negative upon re-test at least 42 days later. 'Persistent positive' is defined as positive at 2 or more timepoints separated by at least 42 days. The threshold for classifying a sample as 'antibody positive' was set at the lowest level of reactivity that had a measurable impact on drug serum concentrations.
Secondary Outcome Measures
Full Information
NCT ID
NCT00306592
First Posted
January 31, 2006
Last Updated
February 14, 2017
Sponsor
Biogen
Collaborators
Elan Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT00306592
Brief Title
Natalizumab 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, or C-1803 and a Dosing Suspension Safety Evaluation
Study Type
Interventional
2. Study Status
Record Verification Date
February 2017
Overall Recruitment Status
Completed
Study Start Date
March 2006 (undefined)
Primary Completion Date
December 2007 (Actual)
Study Completion Date
February 2008 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Biogen
Collaborators
Elan Pharmaceuticals
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objectives of this study are to further evaluate the safety of natalizumab (Tysabri®) monotherapy by evaluating the risk of hypersensitivity and immunogenicity following re-exposure to natalizumab, and to confirm the safety of switching to natalizumab from interferon beta (IFN-β), glatiramer acetate (GA), or other multiple sclerosis (MS) therapies.
Detailed Description
Study 101-MS-322 (NCT00306592) is conducted to evaluate the safety of natalizumab monotherapy following re-exposure to natalizumab of former clinical trial participants in Studies C-1801 (NCT00027300), C-1802 (NCT00030966), and C-1803 (NCT00097760). This study includes participants in North America. In parallel with the conduct of this study, a similar study, 101-MS-321 (NCT00297232) is initiated for participants in Europe and the rest of the world. The primary purpose and primary outcome for both studies are identical, therefore, the combined Week 48 data from both studies are presented. In addition, after 48 weeks, participants from 101-MS-322 (NCT00306592) can enter study 101-MS-321 (NCT 00297232), which is considered the Long-Term Treatment Period of 101-MS-322 (NCT00306592).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis, Relapsing-Remitting
Keywords
Multiple Sclerosis, MS
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
404 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Natalizumab
Arm Type
Experimental
Arm Description
All study participants in 101-MS-322 (NCT00306592) and 101-MS-321 (NCT00297232) received open label 300 mg intravenous (IV) natalizumab 60-minute infusion once every 4 weeks (28 days ±7 days) for up to 48 weeks. After 48 weeks, participants from 101-MS-322 (NCT00306592) entering study 101-MS-321 (NCT 00297232; considered the Long-Term Treatment Period of 101-MS-322) were continued on treatment from Week 52 through Week 480.
Intervention Type
Biological
Intervention Name(s)
BG00002 (natalizumab)
Other Intervention Name(s)
Tysabri
Primary Outcome Measure Information:
Title
Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious AEs (SAEs)
Description
AEs: any sign, symptom, or diagnosis/disease that is unfavorable or unintended, that is new, or if pre-existing, worsens in participants administered a pharmaceutical product and that does not necessarily have a causal relationship with this treatment. SAEs: an event that results in death; an event that, in the view of the investigator, places the participant at immediate risk of death (a life-threatening event); an outcome that results in a congenital anomaly/birth defect diagnosed in a child of a participant; an event that requires or prolongs inpatient hospitalization; an event that results in persistent or significant disability/incapacity. Any other medically important event that, in the opinion of the investigator, may jeopardize the participant or may require intervention to prevent one of the other outcomes listed in the definition above. Treatment-emergent AEs: events in participants who had received at least 1 dose of study drug, regardless of relationship to study drug.
Time Frame
Baseline through Week 48
Title
Number of Participants With Hypersensitivity-related Adverse Events
Description
For purposes of this analysis, the terms 'hypersensitivity' and 'drug hypersensitivity' were categorized by their temporal relationship to study drug infusion (within 2 hours of the start of the infusion), and were considered equivalent. Hypersensitivity reactions are defined as infusion reactions with the following preferred terms: hypersensitivity not otherwise specified (NOS), anaphylactic reaction, anaphylactoid reaction, dermatitis allergic, drug hypersensitivity, urticaria NOS, vasoconstriction, urticaria generalised, hypersensitivity, urticaria.
Time Frame
Baseline through Week 48
Title
Number of Participants With Antibodies to Natalizumab
Description
'Positive with unknown persistence' is defined as a positive result (≥0.5 micrograms/mL) at one timepoint only with no confirmatory re-test available at least 42 days later. 'Transient positive' is defined as a positive at one timepoint but negative upon re-test at least 42 days later. 'Persistent positive' is defined as positive at 2 or more timepoints separated by at least 42 days. The threshold for classifying a sample as 'antibody positive' was set at the lowest level of reactivity that had a measurable impact on drug serum concentrations.
Time Frame
Baseline (Week 0), Week 4, Week 24 (test was repeated after 8 weeks if positive, to confirm persistence)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
MS subjects who completed Study C-1801 (NCT00027300), C-1802 (NCT00030966), or C-1803 (NCT00097760) and completed a Dosing Suspension Safety Evaluation (neurological examination and magnetic resonance imaging [MRI] scan)
Considered by the investigator to be free of signs and symptoms suggestive of progressive multifocal leukoencephalopathy (PML) based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety Evaluation from Study C-1808 [NCT000276172] may be used)
Other protocol-defined inclusion criteria may apply
Exclusion Criteria:
Considered by the investigator to be immunocompromised, based on medical history, physical examination, or laboratory testing (results from the Dosing Suspension Safety Evaluation from Study C-1808 may be used), or due to prior immunosuppressive treatment
History of persistent anti-natalizumab antibodies, based upon testing from prior natalizumab studies
Other protocol-defined exclusion criteria may apply
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Director
Organizational Affiliation
Biogen
Official's Role
Study Director
Facility Information:
Facility Name
Research Site
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35233
Country
United States
Facility Name
Research Site
City
Phoenix
State/Province
Arizona
ZIP/Postal Code
85006
Country
United States
Facility Name
Research Site
City
Scottsdale
State/Province
Arizona
ZIP/Postal Code
85259
Country
United States
Facility Name
Research Site
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72205
Country
United States
Facility Name
Research Site
City
Berkeley
State/Province
California
ZIP/Postal Code
94705
Country
United States
Facility Name
Research Site
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
Research Site
City
Redwood City
State/Province
California
ZIP/Postal Code
94063
Country
United States
Facility Name
Research Site
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
Research Site
City
San Francisco
State/Province
California
ZIP/Postal Code
94117
Country
United States
Facility Name
Research Site
City
Colorado Springs
State/Province
Colorado
ZIP/Postal Code
80919
Country
United States
Facility Name
Research Site
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
Research Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Research Site
City
Maitland
State/Province
Florida
ZIP/Postal Code
32751
Country
United States
Facility Name
Research Site
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Research Site
City
Pompano Beach
State/Province
Florida
ZIP/Postal Code
33060
Country
United States
Facility Name
Research Site
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30327
Country
United States
Facility Name
Research Site
City
Arlington
State/Province
Illinois
ZIP/Postal Code
60007
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Research Site
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Research Site
City
Northbrook
State/Province
Illinois
ZIP/Postal Code
60062
Country
United States
Facility Name
Research Site
City
Des Moines
State/Province
Iowa
ZIP/Postal Code
50314
Country
United States
Facility Name
Research Site
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States
Facility Name
Research Site
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Research Site
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
01655
Country
United States
Facility Name
Research Site
City
East Lansing
State/Province
Michigan
ZIP/Postal Code
48824
Country
United States
Facility Name
Research Site
City
Farmington Hills
State/Province
Michigan
ZIP/Postal Code
48334
Country
United States
Facility Name
Research Site
City
Teaneck
State/Province
New Jersey
ZIP/Postal Code
07666
Country
United States
Facility Name
Research Site
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Research Site
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Research Site
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Research Site
City
Great Neck
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10003
Country
United States
Facility Name
Research Site
City
New York
State/Province
New York
ZIP/Postal Code
10319
Country
United States
Facility Name
Research Site
City
Staten Island
State/Province
New York
ZIP/Postal Code
10305
Country
United States
Facility Name
Research Site
City
Syracuse
State/Province
New York
ZIP/Postal Code
13202
Country
United States
Facility Name
Research Site
City
Charlotte
State/Province
North Carolina
ZIP/Postal Code
28207
Country
United States
Facility Name
Research Site
City
Raleigh
State/Province
North Carolina
ZIP/Postal Code
27607
Country
United States
Facility Name
Research Site
City
Fargo
State/Province
North Dakota
ZIP/Postal Code
58103
Country
United States
Facility Name
Research Site
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Research Site
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Facility Name
Research Site
City
Portland
State/Province
Oregon
ZIP/Postal Code
97225
Country
United States
Facility Name
Research Site
City
Allentown
State/Province
Pennsylvania
ZIP/Postal Code
18103
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Research Site
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19146
Country
United States
Facility Name
Research Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15212
Country
United States
Facility Name
Research Site
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15213
Country
United States
Facility Name
Research Site
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38163
Country
United States
Facility Name
Research Site
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37215
Country
United States
Facility Name
Research Site
City
Dallas
State/Province
Texas
ZIP/Postal Code
75214
Country
United States
Facility Name
Research Site
City
Round Rock
State/Province
Texas
ZIP/Postal Code
78681
Country
United States
Facility Name
Research Site
City
Burlington
State/Province
Vermont
ZIP/Postal Code
05401
Country
United States
Facility Name
Research Site
City
Charlottesville
State/Province
Virginia
ZIP/Postal Code
22903
Country
United States
Facility Name
Research Site
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53215
Country
United States
Facility Name
Research Site
City
Vancouver
State/Province
British Columbia
ZIP/Postal Code
V6T2B5
Country
Canada
Facility Name
Research Site
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3H1V7
Country
Canada
Facility Name
Research Site
City
Kingston
State/Province
Ontario
ZIP/Postal Code
K7L2V7
Country
Canada
Facility Name
Research Site
City
London
State/Province
Ontario
ZIP/Postal Code
N6A5A5
Country
Canada
Facility Name
Research Center
City
New York
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Facility Name
Research Site
City
Ottawa
State/Province
Ontario
ZIP/Postal Code
K2G6E2
Country
Canada
Facility Name
Research Site
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5B1W8
Country
Canada
Facility Name
Research Site
City
Gatineau
State/Province
Quebec
ZIP/Postal Code
J8Y1W7
Country
Canada
Facility Name
Research Site
City
Greenfield Park
State/Province
Quebec
ZIP/Postal Code
J4V2H1
Country
Canada
Facility Name
Research Site
City
Montreal
State/Province
Quebec
ZIP/Postal Code
H3A2B4
Country
Canada
12. IPD Sharing Statement
Citations:
PubMed Identifier
24898925
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. Erratum In: Neurology. 2014 Aug 19;83(8):773.
Results Reference
background
Links:
URL
http://www.nationalmssociety.org
Description
The website of the National Multiple Sclerosis Society, an organization dedicated to providing information to individuals with MS, their families, and healthcare providers.)
URL
http://www.msactivesource.com
Description
(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.)
Learn more about this trial
Natalizumab Re-Initiation of Dosing
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