Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
MS
Brief summary
This is a randomized, rater blinded trial in patients who interrupt treatment with natalizumab with or without being treated with other immunomodulatory drugs, or continue treatment with natalizumab. The main purpose of this study is to find out the following, when participants stop taking natalizumab for 24 weeks: * when MS symptoms return, and * if other drugs for MS may help control MS symptoms during the natalizumab-interruption period. This study will also explore how quickly the effects of natalizumab return after resuming natalizumab dosing.
Interventions
DRUGglatiramer acetate
20 mg subcutaneous once daily
DRUGnatalizumab
300 mg intravenous every 4 weeks
30 ug intramuscular once per week
DRUGmethylprednisolone
1000 mg intravenous every 4 weeks
OTHERIV placebo
placebo intravenous every 4 weeks
Sponsors
Elan Pharmaceuticals
Biogen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
Major criteria include: * A diagnosis of a relapsing form of MS * Treatment with natalizumab according to locally approved prescribing information * Other protocol defined inclusion/
Exclusion criteria
may apply
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 28 Weeks | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 28 Weeks | 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. |
Countries
Germany, Spain, United States
Participant flow
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.
Participants by arm
| Arm | Count |
|---|---|
| Natalizumab 300 mg intravenous every 4 weeks | 45 |
| Intravenous Placebo placebo matching natalizumab, intravenous every 4 weeks | 42 |
| Interferon β-1a 30 ug intramuscular once per week | 17 |
| Glatiramer Acetate 20 mg subcutaneous once daily | 17 |
| Methylprednisolone 1000 mg intravenous every 4 weeks | 54 |
| Total | 175 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 |
|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 1 | 0 | 1 |
| Overall Study | Did Not Meet Eligibility Criteria | 0 | 0 | 1 | 1 | 1 |
| Overall Study | Did Not Want Per Protocol Treatment | 0 | 0 | 1 | 0 | 1 |
| Overall Study | Early Rescue | 1 | 0 | 0 | 0 | 1 |
| Overall Study | Images Not Usable (Motion) | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Physician Decision | 1 | 0 | 0 | 1 | 1 |
| Overall Study | Subject Moved | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Subject Refused to Continue | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 0 | 2 | 0 | 3 |
Baseline characteristics
| Characteristic | Natalizumab | Intravenous Placebo | Interferon β-1a | Glatiramer Acetate | Methylprednisolone | Total |
|---|---|---|---|---|---|---|
| Age Continuous | 41.2 Years STANDARD_DEVIATION 9.7 | 40.0 Years STANDARD_DEVIATION 10.36 | 45.1 Years STANDARD_DEVIATION 9.92 | 44.1 Years STANDARD_DEVIATION 7.85 | 40.1 Years STANDARD_DEVIATION 9.96 | 41.2 Years STANDARD_DEVIATION 9.85 |
| Sex: Female, Male Female | 37 Participants | 31 Participants | 14 Participants | 14 Participants | 39 Participants | 135 Participants |
| Sex: Female, Male Male | 8 Participants | 11 Participants | 3 Participants | 3 Participants | 15 Participants | 40 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 35 / — | 38 / — | 15 / — | 15 / — | 42 / — |
| serious Total, serious adverse events | 1 / — | 1 / — | 1 / — | 1 / — | 1 / — |
Outcome results
Primary
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.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | 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. | 4.7 Percentage of subjects meeting criteria |
| Intravenous Placebo | 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. | 60.5 Percentage of subjects meeting criteria |
| Interferon β-1a | 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. | 28.6 Percentage of subjects meeting criteria |
| Glatiramer Acetate | 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. | 53.3 Percentage of subjects meeting criteria |
| Methylprednisolone | 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. | 54.8 Percentage of subjects meeting criteria |
Secondary
Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria.
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
Population: 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 | Measure | Value (NUMBER) |
|---|---|---|
| Natalizumab | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 0.0 Percentage of subjects meeting criteria |
| Intravenous Placebo | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 52.5 Percentage of subjects meeting criteria |
| Interferon β-1a | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 8.3 Percentage of subjects meeting criteria |
| Glatiramer Acetate | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 49.7 Percentage of subjects meeting criteria |
| Methylprednisolone | Time Course to Return of Radiological Activity, as Measured by the Percentage of Subjects Who Met Magnetic Resonance Imaging (MRI) Rescue Criteria. | 46.1 Percentage of subjects meeting criteria |