Clinical trial NCT02775110: Natalizumab Temporary Discontinuation Study
Official title: Natalizumab Temporary Discontinuation Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Multiple Sclerosis
Lead sponsor: University at Buffalo
Sponsor class: OTHER
First posted: 2016-05-17
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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 exclusion criteria

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

Primary outcomes:
measure: Number of recorded infections including viral opportunistic infection
timeFrame: Up to 1 year follow-up
measure: Saturation percentage of α4β1integrin receptors on the surface of lymphocytes
timeFrame: 12 months
measure: Number gadolinium-enhancing lesions
timeFrame: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
measure: Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints
timeFrame: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
measure: Sum of new and enlarging T2-weighted lesions
timeFrame: Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Secondary outcomes:
measure: Number of clinical relapses
timeFrame: Either baseline (immediate discontinuation group) or 6 months (taper-off group)
measure: Expanded Disability Status Scale (EDSS) score
timeFrame: Either baseline (immediate discontinuation group) or 6 months (taper-off group)
Other outcomes:
Locations:
city: Buffalo
country: United States
facility: Buffalo Neuroimaging Analysis Center
state: New York
city: Buffalo
country: United States
facility: Jacobs Neurological Institute
state: New York
Study officials:
affiliation: Jacob's Neurological Institute
name: Bianca Weinstock-Guttman, MD
role: PRINCIPAL_INVESTIGATOR
References: