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Treatment Interruption of Natalizumab (RESTORE)

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ClinicalTrials.gov Identifier: NCT01071083
Recruitment Status : Completed
First Posted : February 19, 2010
Results First Posted : January 30, 2013
Last Update Posted : September 19, 2013
Sponsor:
Collaborator:
Elan Pharmaceuticals
Information provided by (Responsible Party):
Biogen

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Condition Relapsing Remitting Multiple Sclerosis
Interventions Drug: natalizumab
Drug: interferon beta 1-a
Drug: methylprednisolone
Other: IV placebo
Drug: glatiramer acetate
Enrollment 175
Recruitment Details Date of first treatment: 31 March 2010. Date of study completion: 02 November 2011.
Pre-assignment Details 175 subjects were enrolled, all 175 were randomized.
Arm/Group Title Intravenous Placebo Natalizumab Interferon β-1a Glatiramer Acetate Methylprednisolone
Hide Arm/Group Description placebo matching natalizumab, intravenous every 4 weeks 300 mg intravenous every 4 weeks 30 ug intramuscular once per week 20 mg subcutaneous once daily 1000 mg intravenous every 4 weeks
Period Title: Overall Study
Started 42 45 17 17 54
Completed 35 43 12 15 46
Not Completed 7 2 5 2 8
Reason Not Completed
Adverse Event             1             0             1             0             1
Withdrawal by Subject             3             0             2             0             3
Physician Decision             1             0             0             1             1
Early Rescue             1             0             0             0             1
Subject Moved             0             1             0             0             0
Images Not Usable (Motion)             0             1             0             0             0
Did Not Meet Eligibility Criteria             0             0             1             1             1
Did Not Want Per Protocol Treatment             0             0             1             0             1
Subject Refused to Continue             1             0             0             0             0
Arm/Group Title Natalizumab Intravenous Placebo Interferon β-1a Glatiramer Acetate Methylprednisolone Total
Hide Arm/Group Description 300 mg intravenous every 4 weeks placebo matching natalizumab, intravenous every 4 weeks 30 ug intramuscular once per week 20 mg subcutaneous once daily 1000 mg intravenous every 4 weeks Total of all reporting groups
Overall Number of Baseline Participants 45 42 17 17 54 175
Hide Baseline Analysis Population Description
[Not Specified]
Age Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 45 participants 42 participants 17 participants 17 participants 54 participants 175 participants
41.2  (9.70) 40.0  (10.36) 45.1  (9.92) 44.1  (7.85) 40.1  (9.96) 41.2  (9.85)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 45 participants 42 participants 17 participants 17 participants 54 participants 175 participants
Female
37
  82.2%
31
  73.8%
14
  82.4%
14
  82.4%
39
  72.2%
135
  77.1%
Male
8
  17.8%
11
  26.2%
3
  17.6%
3
  17.6%
15
  27.8%
40
  22.9%
1.Primary Outcome
Title Time Course to Return of Radiological and/or Clinical Evidence of Multiple Sclerosis Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) and/or Clinical Relapse Rescue Criteria.
Hide Description Rescue criteria were: 1) central reader MRI finding of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size 2) clinical relapse. Clinical relapse was new or recurrent neurological symptoms not associated with fever or infection, lasting at least 24 hours, as defined by: an increase of ≥1 grade in ≥2 functional scales of the Expanded Disability Status Scale (EDSS); an increase of ≥2 grades in 1 functional scale of the EDSS; or an increase of >0.5 in EDSS if the previous EDSS was ≤5.5, or ≥0.5 if the previous EDSS was >5.5
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the randomized subjects, data from 167 subjects were used in efficacy analyses. Eight subjects were excluded from the analyses: 3 subjects had major protocol deviations and 5 subjects discontinued study participation prior to Week 4 Visit.
Arm/Group Title Natalizumab Intravenous Placebo Interferon β-1a Glatiramer Acetate Methylprednisolone
Hide Arm/Group Description:
300 mg intravenous every 4 weeks
placebo matching natalizumab, intravenous every 4 weeks
30 ug intramuscular once per week
20 mg subcutaneous once daily
1000 mg intravenous every 4 weeks
Overall Number of Participants Analyzed 45 41 14 15 52
Measure Type: Number
Unit of Measure: Percentage of subjects meeting criteria
4.7 60.5 28.6 53.3 54.8
2.Secondary Outcome
Title Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria.
Hide Description MRI rescue criteria were the presence of 1 new gadolinium-enhancing (Gd+) lesion of >0.8 cubic centimeters in volume or 2 or more Gd+ lesions of any size, according to the central MRI reader.
Time Frame 28 Weeks
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Of the randomized subjects, data from 167 subjects were used in efficacy analyses. Eight subjects were excluded from the analyses: 3 subjects had major protocol deviations and 5 subjects discontinued study participation prior to Week 4 Visit.
Arm/Group Title Natalizumab Intravenous Placebo Interferon β-1a Glatiramer Acetate Methylprednisolone
Hide Arm/Group Description:
300 mg intravenous every 4 weeks
placebo matching natalizumab, intravenous every 4 weeks
30 ug intramuscular once per week
20 mg subcutaneous once daily
1000 mg intravenous every 4 weeks
Overall Number of Participants Analyzed 45 41 14 15 52
Measure Type: Number
Unit of Measure: Percentage of subjects meeting criteria
0.0 52.5 8.3 49.7 46.1
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Intravenous Placebo Natalizumab Interferon β-1a Glatiramer Acetate Methylprednisolone
Hide Arm/Group Description placebo matching natalizumab, intravenous every 4 weeks 300 mg intravenous every 4 weeks 30 ug intramuscular once per week 20 mg subcutaneous once daily 1000 mg intravenous every 4 weeks
All-Cause Mortality
Intravenous Placebo Natalizumab Interferon β-1a Glatiramer Acetate Methylprednisolone
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Intravenous Placebo Natalizumab Interferon β-1a Glatiramer Acetate Methylprednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   1      1      1      1      1    
General disorders           
Chest Pain   0/42 (0.00%)  0 1/45 (2.22%)  1 0/17 (0.00%)  0 0/17 (0.00%)  0 0/54 (0.00%)  0
Infections and infestations           
Brain Abscess   0/42 (0.00%)  0 0/45 (0.00%)  0 0/17 (0.00%)  0 0/17 (0.00%)  0 1/54 (1.85%)  1
Nervous system disorders           
Multiple Sclerosis   1/42 (2.38%)  1 0/45 (0.00%)  0 0/17 (0.00%)  0 0/17 (0.00%)  0 0/54 (0.00%)  0
Multiple Sclerosis Relapse   0/42 (0.00%)  0 0/45 (0.00%)  0 0/17 (0.00%)  0 1/17 (5.88%)  2 0/54 (0.00%)  0
Syncope   0/42 (0.00%)  0 0/45 (0.00%)  0 1/17 (5.88%)  1 0/17 (0.00%)  0 0/54 (0.00%)  0
Presyncope   0/42 (0.00%)  0 0/45 (0.00%)  0 1/17 (5.88%)  2 0/17 (0.00%)  0 0/54 (0.00%)  0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Intravenous Placebo Natalizumab Interferon β-1a Glatiramer Acetate Methylprednisolone
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   35      38      15      15      42    
Blood and lymphatic system disorders           
LYMPHADENOPATHY   0/42 (0.00%)  3/45 (6.67%)  0/17 (0.00%)  0/17 (0.00%)  1/54 (1.85%) 
Gastrointestinal disorders           
TONGUE CYST   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
CONSTIPATION   0/42 (0.00%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
NAUSEA   0/42 (0.00%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
General disorders           
INFLUENZA LIKE ILLNESS   0/42 (0.00%)  0/45 (0.00%)  5/17 (29.41%)  1/17 (5.88%)  0/54 (0.00%) 
GAIT DISTURBANCE   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
INJECTION SITE HAEMATOMA   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
ASTHENIA   0/42 (0.00%)  0/45 (0.00%)  2/17 (11.76%)  0/17 (0.00%)  0/54 (0.00%) 
INJECTION SITE URTICARIA   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
FATIGUE   6/42 (14.29%)  2/45 (4.44%)  1/17 (5.88%)  2/17 (11.76%)  2/54 (3.70%) 
INJECTION SITE PAIN   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
Immune system disorders           
DRUG HYPERSENSITIVITY   0/42 (0.00%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Infections and infestations           
URINARY TRACT INFECTION   5/42 (11.90%)  1/45 (2.22%)  2/17 (11.76%)  1/17 (5.88%)  2/54 (3.70%) 
INFLUENZA   1/42 (2.38%)  1/45 (2.22%)  0/17 (0.00%)  0/17 (0.00%)  3/54 (5.56%) 
VULVOVAGINAL CANDIDIASIS   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
UPPER RESPIRATORY TRACT INFECTION   6/42 (14.29%)  3/45 (6.67%)  0/17 (0.00%)  3/17 (17.65%)  6/54 (11.11%) 
NASOPHARYNGITIS   5/42 (11.90%)  11/45 (24.44%)  4/17 (23.53%)  1/17 (5.88%)  5/54 (9.26%) 
FUNGAL SKIN INFECTION   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
PYELONEPHRITIS   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
Injury, poisoning and procedural complications           
INCISION SITE PAIN   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
POST LUMBAR PUNCTURE SYNDROME   1/42 (2.38%)  0/45 (0.00%)  2/17 (11.76%)  0/17 (0.00%)  2/54 (3.70%) 
CONCUSSION   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
LACERATION   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  1/54 (1.85%) 
FALL   2/42 (4.76%)  1/45 (2.22%)  1/17 (5.88%)  1/17 (5.88%)  0/54 (0.00%) 
CONTUSION   1/42 (2.38%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Investigations           
BLOOD GLUCOSE INCREASED   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
DRUG SPECIFIC ANTIBODY PRESENT   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
PROTEIN URINE PRESENT   0/42 (0.00%)  1/45 (2.22%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
ALANINE AMINOTRANSFERASE INCREASED   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
GAMMA-GLUTAMYLTRANSFERASE INCREASED   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
WHITE BLOOD CELLS URINE POSITIVE   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
LYMPHOCYTE MORPHOLOGY ABNORMAL   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
EOSINOPHIL COUNT INCREASED   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Metabolism and nutrition disorders           
FOLATE DEFICIENCY   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
IRON DEFICIENCY   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
VITAMIN D DEFICIENCY   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
DEHYDRATION   0/42 (0.00%)  1/45 (2.22%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
Musculoskeletal and connective tissue disorders           
BACK PAIN   1/42 (2.38%)  2/45 (4.44%)  0/17 (0.00%)  0/17 (0.00%)  3/54 (5.56%) 
MUSCLE SPASMS   0/42 (0.00%)  0/45 (0.00%)  2/17 (11.76%)  1/17 (5.88%)  0/54 (0.00%) 
MUSCULAR WEAKNESS   4/42 (9.52%)  2/45 (4.44%)  0/17 (0.00%)  0/17 (0.00%)  1/54 (1.85%) 
PAIN IN EXTREMITY   1/42 (2.38%)  3/45 (6.67%)  0/17 (0.00%)  2/17 (11.76%)  1/54 (1.85%) 
ARTHRALGIA   2/42 (4.76%)  1/45 (2.22%)  0/17 (0.00%)  1/17 (5.88%)  2/54 (3.70%) 
JOINT STIFFNESS   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  1/17 (5.88%)  0/54 (0.00%) 
Nervous system disorders           
SYNCOPE   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  1/54 (1.85%) 
MEMORY IMPAIRMENT   2/42 (4.76%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
HYPOAESTHESIA   2/42 (4.76%)  3/45 (6.67%)  1/17 (5.88%)  1/17 (5.88%)  0/54 (0.00%) 
HYPERREFLEXIA   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
COGNITIVE DISORDER   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
ANTICHOLINERGIC SYNDROME   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
MULTIPLE SCLEROSIS RELAPSE   8/42 (19.05%)  2/45 (4.44%)  4/17 (23.53%)  4/17 (23.53%)  11/54 (20.37%) 
NEURALGIA   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
DIZZINESS   0/42 (0.00%)  3/45 (6.67%)  0/17 (0.00%)  0/17 (0.00%)  0/54 (0.00%) 
MIGRAINE   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
LHERMITTE’S SIGN   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
BURNING FEET SYNDROME   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
HEADACHE   3/42 (7.14%)  8/45 (17.78%)  1/17 (5.88%)  1/17 (5.88%)  3/54 (5.56%) 
PRESYNCOPE   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
DYSGEUSIA   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
PARAESTHESIA   3/42 (7.14%)  3/45 (6.67%)  0/17 (0.00%)  0/17 (0.00%)  0/54 (0.00%) 
BALANCE DISORDER   1/42 (2.38%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
Psychiatric disorders           
SLEEP DISORDER   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  3/54 (5.56%) 
HALLUCINATION, VISUAL   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
PANIC ATTACK   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
ANXIETY   2/42 (4.76%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  1/54 (1.85%) 
DEPRESSION   2/42 (4.76%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Reproductive system and breast disorders           
BREAST CYST   0/42 (0.00%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Respiratory, thoracic and mediastinal disorders           
DYSPNOEA   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
OROPHARYNGEAL PAIN   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  3/54 (5.56%) 
INCREASED UPPER AIRWAY SECRETION   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
SINUS CONGESTION   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
PRODUCTIVE COUGH   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Skin and subcutaneous tissue disorders           
RASH   0/42 (0.00%)  1/45 (2.22%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
ECZEMA   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
SKIN LESION   0/42 (0.00%)  0/45 (0.00%)  0/17 (0.00%)  1/17 (5.88%)  0/54 (0.00%) 
Vascular disorders           
HYPERTENSION   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
HYPOTENSION   0/42 (0.00%)  0/45 (0.00%)  1/17 (5.88%)  0/17 (0.00%)  0/54 (0.00%) 
Indicates events were collected by systematic assessment
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.
The provisions of our agreement are 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 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
Name/Title: Biogen Idec Medical Director
Organization: Biogen Idec Inc
Phone: 1-617-679-2000
Responsible Party: Biogen
ClinicalTrials.gov Identifier: NCT01071083     History of Changes
Other Study ID Numbers: 101MS205
First Submitted: February 17, 2010
First Posted: February 19, 2010
Results First Submitted: October 25, 2012
Results First Posted: January 30, 2013
Last Update Posted: September 19, 2013