Multiple Sclerosis
Conditions
Brief summary
This study evaluates the discontinuation of natalizumab either immediately or tapered off in the treatment of multiple sclerosis. Half of the fifty (50) participants will discontinue natalizumab immediately and the other half will taper off the drug, having two additional infusions, one at six weeks- and one at eight weeks-post discontinuation.
Detailed description
Natalizumab is a pharmaceutical intervention used in the management of multiple sclerosis. The decision to discontinue natalizumab therapy is often raised in patients defined as high-risk for PML despite good clinical efficacy. During the therapy cessation period following large phase III trials, a return to the prestudy disease activity was reached by four months post-discontinuation. Shorter therapy was associated with a trend for a more severe disease activity pointing to a possible 'rebound' effect after natalizumab discontinuation. This study focuses on two different approaches: an immediate versus a step-wise/tapered down natalizumab discontinuation protocol, both with reinstitution of a different disease modifying therapy (DMT) within 1-6 months from the last natalizumab infusion.
Interventions
OTHERNatalizumab discontinuation
Patients will be randomized to one of two groups: The Immediate Discontinuation Group (stop natalizumab immediately and continue with new DMT 1 month afterward) and the Taper-off Group (two additional infusions of natalizumab, one at 6 weeks and the next at 8 weeks following discontinuation. A new DMT will be initiated within 2 months of final natalizumab infusion).
Sponsors
University at Buffalo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient with relapsing-remitting or relapsing-progressive (relapsing-remitting with incomplete recovery and secondary progressive with superimposed relapses) MS according to the McDonald criteria who have been on natalizumab therapy for at least 12 months * Age 18-65 * Have EDSS scores less than or equal to 7.0 * Positive John Cunningham (JC) virus antibody results at screening * Signed informed consent * None of the
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Saturation percentage of α4β1integrin receptors on the surface of lymphocytes | 12 months | — |
| Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints | Change between baseline-6 months, 6 months-12 months, and baseline-12 months | Absolute changes in gadolinium-enhancing and T2-weighted lesion volume |
| Sum of new and enlarging T2-weighted lesions | Change between baseline-6 months, 6 months-12 months, and baseline-12 months | Sum of new and enlarging lesions as seen on T2-weighted images |
| Number of recorded infections including viral opportunistic infection | Up to 1 year follow-up | Number of recorded infections including viral opportunistic infections (i.e., shingles) will be recorded up to 1-year follow-up; continuous close vigilance will be maintained for possible cases of progressive multifocal leukoencephalopathy (PML) |
| Number gadolinium-enhancing lesions | Change between baseline-6 months, 6 months-12 months, and baseline-12 months | Number of gadolinium-enhancing lesions |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expanded Disability Status Scale (EDSS) score | Either baseline (immediate discontinuation group) or 6 months (taper-off group) | Expanded disability status scale score |
| Number of clinical relapses | Either baseline (immediate discontinuation group) or 6 months (taper-off group) | Number of clinical relapses will be assessed at the time of natalizumab therapy discontinuation which will be different between the two groups |
Countries
United States
Outcome results
None listed