Back to resultsNatalizumab Temporary Discontinuation Study (NaTDS)
Primary Purpose
Multiple Sclerosis
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Natalizumab discontinuation
Sponsored by
About this trial
This is an interventional supportive care trial for Multiple Sclerosis
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
Sites / Locations
- Buffalo Neuroimaging Analysis Center
- Jacobs Neurological Institute
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Experimental
Arm Label
Immediate Discontinuation Group
Taper-off Group
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Number of recorded infections including viral opportunistic infection
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)
Saturation percentage of α4β1integrin receptors on the surface of lymphocytes
Number gadolinium-enhancing lesions
Number of gadolinium-enhancing lesions
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume
Sum of new and enlarging T2-weighted lesions
Sum of new and enlarging lesions as seen on T2-weighted images
Secondary Outcome Measures
Number of clinical relapses
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
Expanded disability status scale score
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02775110
Brief Title
Natalizumab Temporary Discontinuation Study
Acronym
NaTDS
Official Title
Natalizumab Temporary Discontinuation Study
Study Type
Interventional
2. Study Status
Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
November 2012 (undefined)
Primary Completion Date
March 2014 (Actual)
Study Completion Date
March 2014 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University at Buffalo
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
7. Study Design
Primary Purpose
Supportive Care
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Immediate Discontinuation Group
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Taper-off Group
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Natalizumab discontinuation
Intervention Description
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).
Primary Outcome Measure Information:
Title
Number of recorded infections including viral opportunistic infection
Description
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)
Time Frame
Up to 1 year follow-up
Title
Saturation percentage of α4β1integrin receptors on the surface of lymphocytes
Time Frame
12 months
Title
Number gadolinium-enhancing lesions
Description
Number of gadolinium-enhancing lesions
Time Frame
Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Title
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints
Description
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume
Time Frame
Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Title
Sum of new and enlarging T2-weighted lesions
Description
Sum of new and enlarging lesions as seen on T2-weighted images
Time Frame
Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Secondary Outcome Measure Information:
Title
Number of clinical relapses
Description
Number of clinical relapses will be assessed at the time of natalizumab therapy discontinuation which will be different between the two groups
Time Frame
Either baseline (immediate discontinuation group) or 6 months (taper-off group)
Title
Expanded Disability Status Scale (EDSS) score
Description
Expanded disability status scale score
Time Frame
Either baseline (immediate discontinuation group) or 6 months (taper-off group)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bianca Weinstock-Guttman, MD
Organizational Affiliation
Jacob's Neurological Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
Buffalo Neuroimaging Analysis Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Facility Name
Jacobs Neurological Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Natalizumab Temporary Discontinuation Study
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