Natalizumab Temporary Discontinuation Study
- Conditions
- Multiple Sclerosis
- Interventions
- Other: Natalizumab discontinuation
- Registration Number
- NCT02775110
- Lead Sponsor
- University at Buffalo
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 50
- 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 exclusion criteria
- Patients not willing or able to personally provide informed consent (subjects with cognitive impairment that effects the ability to provide informed consent for participation)
- Patients with active disease per clinical and MRI evaluation at baseline
- Patients with renal disease that precludes having an MRI with gadolinium contrast
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Immediate Discontinuation Group Natalizumab discontinuation Patients will discontinue the natalizumab therapy at once and initiate another disease modifying therapy at 1 month following the last natalizumab infusion. The disease modifying therapy at 1 month following natalizumab discontinuation will be at the discretion of the neurologist and may differ among patients. Taper-off Group Natalizumab discontinuation Patients will be administered two more natalizumab infusion, one at six weeks and the second at eight weeks (14 weeks from study entry), followed by six months natalizumab discontinuation. Another DMT will be initiated within two months after the last natalizumab infusion.
- Primary Outcome Measures
Name Time Method Number gadolinium-enhancing lesions Change between baseline-6 months, 6 months-12 months, and baseline-12 months Number of gadolinium-enhancing lesions
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)
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
Saturation percentage of α4β1integrin receptors on the surface of lymphocytes 12 months 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
- Secondary Outcome Measures
Name Time Method 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
Expanded Disability Status Scale (EDSS) score Either baseline (immediate discontinuation group) or 6 months (taper-off group) Expanded disability status scale score
Trial Locations
- Locations (2)
Jacobs Neurological Institute
🇺🇸Buffalo, New York, United States
Buffalo Neuroimaging Analysis Center
🇺🇸Buffalo, New York, United States