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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00297232
Recruitment Status : Terminated
First Posted : February 28, 2006
Results First Posted : May 29, 2015
Last Update Posted : July 15, 2016
Sponsor:
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Relapsing-Remitting Multiple Sclerosis
Intervention Drug: Natalizumab
Enrollment 1094
Recruitment Details  
Pre-assignment Details

Participants from studies 101-MS-321 (NCT00297232) and 101-MS-322 (NCT00306592) are included in this presentation of combined final data.

Note: In the Participant Flow table, 'progressive multifocal leukoencephalopathy' is abbreviated to 'PML'. and John Cunningham virus is abbreviated to 'JCV'.

Arm/Group Title Natalizumab
Hide Arm/Group Description 300 mg intravenous (IV) infusions once every 4 weeks for up to 480 weeks
Period Title: Overall Study
Started 1094
Completed 489
Not Completed 605
Reason Not Completed
Lack of Efficacy             7
Lost to Follow-up             10
Adverse Event             63
Voluntary Withdrawal             120
Subject was Noncompliant             9
Death             9
Anti-natalizumab Positive             8
Switched to Commercial Tysabri             22
Disease Progression             8
Fear of PML             10
Anti-JCV Antibody Positive             13
Miscellaneous             5
Sponsor Decision             34
Subject Relocated             7
Subject Withdrew Consent             37
Persistently Positive Antibodies             11
Investigator Withdrew From Program             19
Did Not Enroll to Week 264             34
Did Not Enroll to Week 480             17
No data available after Week 264             161
Other             1
Arm/Group Title Natalizumab
Hide Arm/Group Description 300 mg IV infusions once every 4 weeks for up to 480 weeks
Overall Number of Baseline Participants 1094
Hide Baseline Analysis Population Description
[Not Specified]
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:  Years
Number Analyzed 1094 participants
20 to 29 years 98
30 to 39 years 347
40 to 49 years 454
50 to 59 years 195
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 Time to 24-week Confirmed Expanded Disability Status Scale (EDSS) Progression
Hide Description 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 Frame up to 480 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with EDSS progression (regardless of length of follow-up) sustained for 24 weeks.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
300 mg IV infusions once every 4 weeks for up to 480 weeks
Overall Number of Participants Analyzed 220
Median (Inter-Quartile Range)
Unit of Measure: weeks
121.9
(67.9 to 216.1)
2.Primary Outcome
Title Time to 48-week Confirmed EDSS Progression
Hide Description 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 Frame up to 480 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with EDSS progression (regardless of length of follow-up) sustained for 48 weeks.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
300 mg IV infusions once every 4 weeks for up to 480 weeks
Overall Number of Participants Analyzed 181
Median (Inter-Quartile Range)
Unit of Measure: weeks
130.1
(72.4 to 216.1)
3.Primary Outcome
Title Time to 24-week Confirmed EDSS Improvement Where Baseline ≥ 2.0
Hide Description 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.
Time Frame Up to 480 weeks
Hide Outcome Measure Data
Hide Analysis Population Description
Participants with EDSS improvement (regardless of length of follow-up) sustained for 24 weeks.
Arm/Group Title Natalizumab
Hide Arm/Group Description:
300 mg IV infusions once every 4 weeks for up to 480 weeks
Overall Number of Participants Analyzed 173
Median (Inter-Quartile Range)
Unit of Measure: weeks
48.1
(24.1 to 119.9)
Time Frame Serious adverse events (SAEs) were collected from screening through the follow-up (492 weeks). Non-serious AEs were collected from baseline through Week 264.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Natalizumab
Hide Arm/Group Description 300 mg IV infusions once every 4 weeks for up to 480 weeks
All-Cause Mortality
Natalizumab
Affected / at Risk (%)
Total   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Natalizumab
Affected / at Risk (%)
Total   231/1094 (21.12%) 
Blood and lymphatic system disorders   
Anaemia  1  1/1094 (0.09%) 
Coombs negative haemolytic anaemia  1  1/1094 (0.09%) 
Immune thrombocytopenic purpura  1  1/1094 (0.09%) 
Splenomegaly  1  1/1094 (0.09%) 
Cardiac disorders   
Atrial fibrillation  1  2/1094 (0.18%) 
Myocardial infarction  1  2/1094 (0.18%) 
Angina pectoris  1  1/1094 (0.09%) 
Coronary artery occlusion  1  1/1094 (0.09%) 
Coronary artery stenosis  1  1/1094 (0.09%) 
Myocardial fibrosis  1  1/1094 (0.09%) 
Sinus tachycardia  1  1/1094 (0.09%) 
Congenital, familial and genetic disorders   
Congenital anomaly  1  1/1094 (0.09%) 
Endocrine disorders   
Goitre  1  1/1094 (0.09%) 
Hyperthyroidism  1  1/1094 (0.09%) 
Eye disorders   
Eye swelling  1  1/1094 (0.09%) 
Glaucoma  1  1/1094 (0.09%) 
Retinal tear  1  1/1094 (0.09%) 
Vision blurred  1  1/1094 (0.09%) 
Gastrointestinal disorders   
Haemorrhoids  1  3/1094 (0.27%) 
Abdominal adhesions  1  2/1094 (0.18%) 
Abdominal pain  1  2/1094 (0.18%) 
Anal fissure  1  2/1094 (0.18%) 
Constipation  1  2/1094 (0.18%) 
Intestinal obstruction  1  2/1094 (0.18%) 
Abdominal hernia  1  1/1094 (0.09%) 
Abdominal pain upper  1  1/1094 (0.09%) 
Colitis ischaemic  1  1/1094 (0.09%) 
Diarrhoea  1  1/1094 (0.09%) 
Diverticular perforation  1  1/1094 (0.09%) 
Duodenitis  1  1/1094 (0.09%) 
Faecaloma  1  1/1094 (0.09%) 
Flatulence  1  1/1094 (0.09%) 
Functional gastrointestinal disorder  1  1/1094 (0.09%) 
Gastric ulcer haemorrhage  1  1/1094 (0.09%) 
Ileus  1  1/1094 (0.09%) 
Inguinal hernia  1  1/1094 (0.09%) 
Irritable bowel syndrome  1  1/1094 (0.09%) 
Large intestine polyp  1  1/1094 (0.09%) 
Oesophageal ulcer  1  1/1094 (0.09%) 
Proctalgia  1  1/1094 (0.09%) 
Rectal prolapse  1  1/1094 (0.09%) 
Small intestinal obstruction  1  1/1094 (0.09%) 
Umbilical hernia  1  1/1094 (0.09%) 
General disorders   
Pyrexia  1  2/1094 (0.18%) 
Chest pain  1  1/1094 (0.09%) 
Fatigue  1  1/1094 (0.09%) 
Multi-organ failure  1  1/1094 (0.09%) 
Oedema  1  1/1094 (0.09%) 
Pain  1  1/1094 (0.09%) 
Polyp  1  1/1094 (0.09%) 
Hepatobiliary disorders   
Cholelithiasis  1  5/1094 (0.46%) 
Cholecystitis  1  2/1094 (0.18%) 
Bile duct stone  1  1/1094 (0.09%) 
Cholecystitis acute  1  1/1094 (0.09%) 
Cholecystitis chronic  1  1/1094 (0.09%) 
Immune system disorders   
Immune reconstitution inflammatory syndrome  1  11/1094 (1.01%) 
Anaphylactic shock  1  2/1094 (0.18%) 
Hypersensitivity  1  2/1094 (0.18%) 
Anaphylactic reaction  1  1/1094 (0.09%) 
Drug hypersensitivity  1  1/1094 (0.09%) 
Infections and infestations   
Progressive multifocal leukoencephalopathy  1  18/1094 (1.65%) 
Urinary tract infection  1  13/1094 (1.19%) 
Pneumonia  1  4/1094 (0.37%) 
Gastroenteritis  1  3/1094 (0.27%) 
Bronchitis viral  1  2/1094 (0.18%) 
Cystitis  1  2/1094 (0.18%) 
Influenza  1  2/1094 (0.18%) 
Staphylococcal infection  1  2/1094 (0.18%) 
Appendicitis  1  1/1094 (0.09%) 
Atypical pneumonia  1  1/1094 (0.09%) 
Bronchitis  1  1/1094 (0.09%) 
Bronchopneumonia  1  1/1094 (0.09%) 
Catheter site infection  1  1/1094 (0.09%) 
Cellulitis  1  1/1094 (0.09%) 
Device related sepsis  1  1/1094 (0.09%) 
Diverticulitis  1  1/1094 (0.09%) 
Epididymitis  1  1/1094 (0.09%) 
Gastroenteritis viral  1  1/1094 (0.09%) 
Hepatitis A  1  1/1094 (0.09%) 
Herpes zoster  1  1/1094 (0.09%) 
Lower respiratory tract infection viral  1  1/1094 (0.09%) 
Lung infection  1  1/1094 (0.09%) 
Meningitis viral  1  1/1094 (0.09%) 
Nasopharyngitis  1  1/1094 (0.09%) 
Oral candidiasis  1  1/1094 (0.09%) 
Pelvic inflammatory disease  1  1/1094 (0.09%) 
Peritonitis  1  1/1094 (0.09%) 
Pharyngitis  1  1/1094 (0.09%) 
Pneumonia pneumococcal  1  1/1094 (0.09%) 
Pneumonia streptococcal  1  1/1094 (0.09%) 
Pyelonephritis  1  1/1094 (0.09%) 
Sinusitis  1  1/1094 (0.09%) 
Tooth abscess  1  1/1094 (0.09%) 
Wound infection  1  1/1094 (0.09%) 
Injury, poisoning and procedural complications   
Fall  1  7/1094 (0.64%) 
Head injury  1  4/1094 (0.37%) 
Lower limb fracture  1  3/1094 (0.27%) 
Concussion  1  2/1094 (0.18%) 
Facial bones fracture  1  2/1094 (0.18%) 
Humerus fracture  1  2/1094 (0.18%) 
Road traffic accident  1  2/1094 (0.18%) 
Wrist fracture  1  2/1094 (0.18%) 
Accidental overdose  1  1/1094 (0.09%) 
Animal bite  1  1/1094 (0.09%) 
Ankle fracture  1  1/1094 (0.09%) 
Arteriovenous fistula site complication  1  1/1094 (0.09%) 
Arthropod bite  1  1/1094 (0.09%) 
Face injury  1  1/1094 (0.09%) 
Femur fracture  1  1/1094 (0.09%) 
Fibula fracture  1  1/1094 (0.09%) 
Foot fracture  1  1/1094 (0.09%) 
Gun shot wound  1  1/1094 (0.09%) 
Hip fracture  1  1/1094 (0.09%) 
Laceration  1  1/1094 (0.09%) 
Lumbar vertebral fracture  1  1/1094 (0.09%) 
Post procedural haemorrhage  1  1/1094 (0.09%) 
Rib fracture  1  1/1094 (0.09%) 
Tendon rupture  1  1/1094 (0.09%) 
Traumatic intracranial haemorrhage  1  1/1094 (0.09%) 
Ulna fracture  1  1/1094 (0.09%) 
Investigations   
Blood pressure increased  1  1/1094 (0.09%) 
Polyomavirus test positive  1  1/1094 (0.09%) 
Metabolism and nutrition disorders   
Diabetes mellitus inadequate control  1  1/1094 (0.09%) 
Musculoskeletal and connective tissue disorders   
Intervertebral disc protrusion  1  5/1094 (0.46%) 
Osteoarthritis  1  3/1094 (0.27%) 
Arthralgia  1  2/1094 (0.18%) 
Spinal column stenosis  1  2/1094 (0.18%) 
Arthritis  1  1/1094 (0.09%) 
Back pain  1  1/1094 (0.09%) 
Bursitis  1  1/1094 (0.09%) 
Joint instability  1  1/1094 (0.09%) 
Joint stiffness  1  1/1094 (0.09%) 
Muscular weakness  1  1/1094 (0.09%) 
Musculoskeletal disorder  1  1/1094 (0.09%) 
Osteonecrosis  1  1/1094 (0.09%) 
Rotator cuff syndrome  1  1/1094 (0.09%) 
Spinal osteoarthritis  1  1/1094 (0.09%) 
Tenosynovitis  1  1/1094 (0.09%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)   
Basal cell carcinoma  1  5/1094 (0.46%) 
Malignant melanoma  1  5/1094 (0.46%) 
Uterine leiomyoma  1  5/1094 (0.46%) 
Intraductal proliferative breast lesion  1  3/1094 (0.27%) 
Breast cancer  1  2/1094 (0.18%) 
Adenocarcinoma of salivary gland  1  1/1094 (0.09%) 
Bile duct adenocarcinoma  1  1/1094 (0.09%) 
Bladder transitional cell carcinoma  1  1/1094 (0.09%) 
Cerebellopontine angle tumour  1  1/1094 (0.09%) 
Colon cancer  1  1/1094 (0.09%) 
Invasive ductal breast carcinoma  1  1/1094 (0.09%) 
Lobular breast carcinoma in situ  1  1/1094 (0.09%) 
Lung adenocarcinoma  1  1/1094 (0.09%) 
Lung neoplasm malignant  1  1/1094 (0.09%) 
Meningioma  1  1/1094 (0.09%) 
Metastatic malignant melanoma  1  1/1094 (0.09%) 
Prostate cancer  1  1/1094 (0.09%) 
Teratoma  1  1/1094 (0.09%) 
Thyroid adenoma  1  1/1094 (0.09%) 
Nervous system disorders   
Multiple sclerosis relapse  1  21/1094 (1.92%) 
Multiple sclerosis  1  2/1094 (0.18%) 
Transient ischaemic attack  1  2/1094 (0.18%) 
Trigeminal neuralgia  1  2/1094 (0.18%) 
Altered state of consciousness  1  1/1094 (0.09%) 
Amnesia  1  1/1094 (0.09%) 
Cerebral cyst  1  1/1094 (0.09%) 
Cerebrovascular insufficiency  1  1/1094 (0.09%) 
Convulsion  1  1/1094 (0.09%) 
Encephalopathy  1  1/1094 (0.09%) 
Epilepsy  1  1/1094 (0.09%) 
Facial neuralgia  1  1/1094 (0.09%) 
Headache  1  1/1094 (0.09%) 
Hypoxic-ischaemic encephalopathy  1  1/1094 (0.09%) 
Migraine  1  1/1094 (0.09%) 
Sciatica  1  1/1094 (0.09%) 
Pregnancy, puerperium and perinatal conditions   
Abortion missed  1  2/1094 (0.18%) 
Abortion spontaneous  1  1/1094 (0.09%) 
Foetal death  1  1/1094 (0.09%) 
Haemorrhage in pregnancy  1  1/1094 (0.09%) 
Premature baby  1  1/1094 (0.09%) 
Psychiatric disorders   
Depression  1  4/1094 (0.37%) 
Suicide attempt  1  3/1094 (0.27%) 
Completed suicide  1  2/1094 (0.18%) 
Mania  1  2/1094 (0.18%) 
Suicidal ideation  1  2/1094 (0.18%) 
Abnormal behaviour  1  1/1094 (0.09%) 
Anxiety disorder  1  1/1094 (0.09%) 
Bipolar I disorder  1  1/1094 (0.09%) 
Confusional state  1  1/1094 (0.09%) 
Obsessive-compulsive disorder  1  1/1094 (0.09%) 
Psychotic disorder  1  1/1094 (0.09%) 
Schizophrenia  1  1/1094 (0.09%) 
Renal and urinary disorders   
Renal colic  1  3/1094 (0.27%) 
Haematuria  1  1/1094 (0.09%) 
Neurogenic bladder  1  1/1094 (0.09%) 
Renal failure acute  1  1/1094 (0.09%) 
Urinary retention  1  1/1094 (0.09%) 
Reproductive system and breast disorders   
Metrorrhagia  1  2/1094 (0.18%) 
Uterine polyp  1  2/1094 (0.18%) 
Adnexal torsion  1  1/1094 (0.09%) 
Breast hyperplasia  1  1/1094 (0.09%) 
Breast mass  1  1/1094 (0.09%) 
Cervical dysplasia  1  1/1094 (0.09%) 
Menometrorrhagia  1  1/1094 (0.09%) 
Menorrhagia  1  1/1094 (0.09%) 
Ovarian cyst  1  1/1094 (0.09%) 
Rectocele  1  1/1094 (0.09%) 
Vaginal prolapse  1  1/1094 (0.09%) 
Respiratory, thoracic and mediastinal disorders   
Nasal polyps  1  2/1094 (0.18%) 
Aspiration  1  1/1094 (0.09%) 
Asthma  1  1/1094 (0.09%) 
Chronic obstructive pulmonary disease  1  1/1094 (0.09%) 
Obstructive airways disorder  1  1/1094 (0.09%) 
Pleural effusion  1  1/1094 (0.09%) 
Pneumonia aspiration  1  1/1094 (0.09%) 
Pneumothorax  1  1/1094 (0.09%) 
Pulmonary embolism  1  1/1094 (0.09%) 
Skin and subcutaneous tissue disorders   
Decubitus ulcer  1  1/1094 (0.09%) 
Melanocytic hyperplasia  1  1/1094 (0.09%) 
Skin disorder  1  1/1094 (0.09%) 
Surgical and medical procedures   
Peripheral nerve decompression  1  1/1094 (0.09%) 
Spinal laminectomy  1  1/1094 (0.09%) 
Thyroid nodule removal  1  1/1094 (0.09%) 
Vascular graft  1  1/1094 (0.09%) 
Vascular disorders   
Deep vein thrombosis  1  2/1094 (0.18%) 
Peripheral ischaemia  1  1/1094 (0.09%) 
Thrombophlebitis  1  1/1094 (0.09%) 
Venous stenosis  1  1/1094 (0.09%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Natalizumab
Affected / at Risk (%)
Total   752/1094 (68.74%) 
Gastrointestinal disorders   
Diarrhoea  1  80/1094 (7.31%) 
General disorders   
Fatigue  1  102/1094 (9.32%) 
Infections and infestations   
Nasopharyngitis  1  256/1094 (23.40%) 
Upper respiratory tract infection  1  192/1094 (17.55%) 
Urinary tract infection  1  162/1094 (14.81%) 
Influenza  1  122/1094 (11.15%) 
Sinusitis  1  82/1094 (7.50%) 
Bronchitis  1  67/1094 (6.12%) 
Injury, poisoning and procedural complications   
Fall  1  61/1094 (5.58%) 
Musculoskeletal and connective tissue disorders   
Back pain  1  113/1094 (10.33%) 
Arthralgia  1  86/1094 (7.86%) 
Pain in extremity  1  62/1094 (5.67%) 
Nervous system disorders   
Multiple sclerosis relapse  1  164/1094 (14.99%) 
Headache  1  157/1094 (14.35%) 
Dizziness  1  62/1094 (5.67%) 
Psychiatric disorders   
Depression  1  72/1094 (6.58%) 
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA 17.0
Sponsor decided to terminate the study prior to all subjects reaching Week 480 as the primary objective was deemed to have been met and only approximately 45% of the original STRATA population remained in the study at the time of study termination.
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 Study Medical Director
Organization: Biogen
EMail: clinicaltrials@biogen.com
Layout table for additonal information
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT00297232     History of Changes
Other Study ID Numbers: 101-MS-321
First Submitted: February 27, 2006
First Posted: February 28, 2006
Results First Submitted: April 21, 2015
Results First Posted: May 29, 2015
Last Update Posted: July 15, 2016