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Natalizumab Re-Initiation of Dosing

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ClinicalTrials.gov Identifier: NCT00306592
Recruitment Status : Completed
First Posted : March 24, 2006
Results First Posted : January 26, 2010
Last Update Posted : March 21, 2017
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Multiple Sclerosis, Relapsing-Remitting
Intervention Biological: BG00002 (natalizumab)
Enrollment 404
Recruitment Details  
Pre-assignment Details Participants from studies 101-MS-321 (NCT00297232) and 101-MS-322 (NCT00306592) are included in this presentation of combined Week 48 data.
Arm/Group Title Natalizumab Study 101-MS-322 (NCT00306592) Natalizumab Study 101-MS-321 (NCT00297232)
Hide Arm/Group Description 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 (NCT00297232; considered the Long-Term Treatment Period of 101-MS-322) were continued on treatment from Week 52 through Week 480. Open label 300 mg intravenous (IV) natalizumab 60-minute infusion once every 4 weeks (28 days ±7 days) for up to 268 weeks. (Week 52 through Week 480 of Study 101-MS-321 (NCT00297232) is considered to be the Long-Term Treatment Period).
Period Title: Overall Study
Started 404 690
Completed at 24 Weeks 207 0
Completed Between 24 and 48 Weeks 85 0
Completed at 48 Weeks 81 632
Entered 101-MS-321 Extension Study 22 0 [1]
Completed 373 632
Not Completed 31 58
Reason Not Completed
Adverse Event             8             15
Lost to Follow-up             1             0
Noncompliance             0             2
Persistent Antibodies             6             3
Voluntary             10             6
Not Specified             5             10
Other             1             2
48-week Treatment Period Ongoing             0             20
[1]
pertains to participants transitioning from 101-MS-322 (NCT00306592) study only
Arm/Group Title 300 mg Natalizumab IV Monthly
Hide Arm/Group 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.
Overall Number of Baseline Participants 1094
Hide Baseline Analysis Population Description
Participants from 101-MS-322 (NCT00306592) and 101-MS-321 (NCT00297232) are combined.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 1094 participants
41.4  (8.12)
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 1094 participants
≥ 18 to < 20 years 0
≥ 20 to < 30 years 98
≥ 30 to < 40 years 347
≥ 40 to < 50 years 454
≥ 50 to < 59 years 195
>/= 60 years 0
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 1094 participants
Female
755
  69.0%
Male
339
  31.0%
1.Primary Outcome
Title Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious AEs (SAEs)
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants receiving at least 1 dose of study drug
Arm/Group Title 300 mg Natalizumab IV Monthly
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1094
Measure Type: Number
Unit of Measure: participants
AE 826
Moderate or severe AE 487
Severe AE 66
AE related to study drug 161
SAE 61
SAE related to study drug 5
Discontinuation of study drug due to AE 24
Withdrawal from study due to AE 24
2.Primary Outcome
Title Number of Participants With Hypersensitivity-related Adverse Events
Hide 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
Hide Outcome Measure Data
Hide Analysis Population Description
Participants receiving at least 1 dose of study drug
Arm/Group Title 300 mg Natalizumab IV Monthly
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1094
Measure Type: Number
Unit of Measure: participants
8
3.Primary Outcome
Title Number of Participants With Antibodies to Natalizumab
Hide 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)
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of natalizumab, had a negative baseline antibody result, and had at least 1 antibody result after the first dose.
Arm/Group Title 300 mg Natalizumab IV Monthly
Hide Arm/Group 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.
Overall Number of Participants Analyzed 1043
Measure Type: Number
Unit of Measure: participants
Antibody negative 1004
Antibody positive with unknown persistence 15
Antibody transient positive 8
Antibody persistent positive 16
Time Frame SAEs were collected from the time of enrollment, and AEs from the time of first dose of natalizumab, until Week 48.
Adverse Event Reporting Description Participants from studies 101-MS-321 (NCT00297232) and 101-MS-322 (NCT00306592) are included in this presentation of combined Week 48 data.
 
Arm/Group Title 300 mg Natalizumab IV Monthly
Hide Arm/Group 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.
All-Cause Mortality
300 mg Natalizumab IV Monthly
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
300 mg Natalizumab IV Monthly
Affected / at Risk (%)
Total   61/1094 (5.58%) 
Cardiac disorders   
Atrial fibrillation  1  1/1094 (0.09%) 
Coronary artery stenosis  1  1/1094 (0.09%) 
Myocardial fibrosis  1  1/1094 (0.09%) 
Gastrointestinal disorders   
Abdominal pain  1  1/1094 (0.09%) 
Hemorrhoids  1  1/1094 (0.09%) 
Small intestine obstruction  1  1/1094 (0.09%) 
Cholecystitis  1  1/1094 (0.09%) 
General disorders   
Fatigue  1  1/1094 (0.09%) 
Pyrexia  1  1/1094 (0.09%) 
Immune system disorders   
Hypersensitivity  1  2/1094 (0.18%) 
Anaphylactic reaction  1  1/1094 (0.09%) 
Anaphylactic shock  1  1/1094 (0.09%) 
Infections and infestations   
Urinary tract infection  1  4/1094 (0.37%) 
Cellulitis  1  1/1094 (0.09%) 
Gastroenteritis  1  1/1094 (0.09%) 
Herpes zoster  1  1/1094 (0.09%) 
Influenza  1  1/1094 (0.09%) 
Lung infection  1  1/1094 (0.09%) 
Viral meningitis  1  1/1094 (0.09%) 
Pyelonephritis  1  1/1094 (0.09%) 
Staphyloccal infection  1  1/1094 (0.09%) 
Injury, poisoning and procedural complications   
Animal bite  1  1/1094 (0.09%) 
Arthropod bite  1  1/1094 (0.09%) 
Head injury  1  1/1094 (0.09%) 
Humerus fracture  1  1/1094 (0.09%) 
Lower limb fracture  1  1/1094 (0.09%) 
Musculoskeletal and connective tissue disorders   
Arthritis  1  1/1094 (0.09%) 
Tenosynovitis  1  1/1094 (0.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Basal cell carcinoma  1  3/1094 (0.27%) 
Thyroid adenoma  1  1/1094 (0.09%) 
Nervous system disorders   
Multiple sclerosis relapse  1  21/1094 (1.92%) 
Pregnancy, puerperium and perinatal conditions   
Intra-uterine death  1  1/1094 (0.09%) 
Psychiatric disorders   
Psychotic disorder  1  1/1094 (0.09%) 
Schizophrenia  1  1/1094 (0.09%) 
Reproductive system and breast disorders   
Ovarian torsion  1  1/1094 (0.09%) 
Respiratory, thoracic and mediastinal disorders   
Asthma  1  1/1094 (0.09%) 
Nasal polyps  1  1/1094 (0.09%) 
Vascular disorders   
Deep vein thrombosis  1  1/1094 (0.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
300 mg Natalizumab IV Monthly
Affected / at Risk (%)
Total   492/1094 (44.97%) 
General disorders   
Fatigue  1  81/1094 (7.40%) 
Infections and infestations   
Nasopharyngitis  1  141/1094 (12.89%) 
Upper respiratory tract infection  1  119/1094 (10.88%) 
Urinary tract infection  1  85/1094 (7.77%) 
Nervous system disorders   
Multiple sclerosis relapse  1  156/1094 (14.26%) 
Headache  1  91/1094 (8.32%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 10.0
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Our agreement is subject to confidentiality but generally the PI can publish, for noncommercial purposes only, results and methods of the trial, but no other Sponsor Confidential Information. PI must give Sponsor no less than 60 days to review any manuscript for a proposed publication and must delay publication for up to an additional 90 days thereafter if Sponsor needs to file any patent application to protect any of Sponsor's intellectual property contained in the proposed publication.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Biogen Idec Study Medical Director
Organization: Biogen Idec
EMail: clinicaltrials@biogenidec.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00306592     History of Changes
Other Study ID Numbers: 101-MS-322
First Submitted: January 31, 2006
First Posted: March 24, 2006
Results First Submitted: June 30, 2009
Results First Posted: January 26, 2010
Last Update Posted: March 21, 2017