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Natalizumab Temporary Discontinuation Study (NaTDS)

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ClinicalTrials.gov Identifier: NCT02775110
Recruitment Status : Completed
First Posted : May 17, 2016
Last Update Posted : May 17, 2016
Sponsor:
Information provided by (Responsible Party):
Robert Zivadinov, MD, PhD, 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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Other: Natalizumab discontinuation Phase 4

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Supportive Care
Official Title: Natalizumab Temporary Discontinuation Study
Study Start Date : November 2012
Actual Primary Completion Date : March 2014
Actual Study Completion Date : March 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Natalizumab

Arm Intervention/treatment
Active Comparator: Immediate Discontinuation Group
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.
Other: Natalizumab 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).

Experimental: Taper-off Group
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.
Other: Natalizumab 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).




Primary Outcome Measures :
  1. Number of recorded infections including viral opportunistic infection [ Time Frame: 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)

  2. Saturation percentage of α4β1integrin receptors on the surface of lymphocytes [ Time Frame: 12 months ]
  3. Number gadolinium-enhancing lesions [ Time Frame: Change between baseline-6 months, 6 months-12 months, and baseline-12 months ]
    Number of gadolinium-enhancing lesions

  4. Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints [ Time Frame: Change between baseline-6 months, 6 months-12 months, and baseline-12 months ]
    Absolute changes in gadolinium-enhancing and T2-weighted lesion volume

  5. Sum of new and enlarging T2-weighted lesions [ Time Frame: 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 :
  1. Number of clinical relapses [ Time Frame: 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

  2. Expanded Disability Status Scale (EDSS) score [ Time Frame: Either baseline (immediate discontinuation group) or 6 months (taper-off group) ]
    Expanded disability status scale score



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02775110


Locations
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United States, New York
Buffalo Neuroimaging Analysis Center
Buffalo, New York, United States, 14203
Jacobs Neurological Institute
Buffalo, New York, United States, 14203
Sponsors and Collaborators
University at Buffalo
Investigators
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Principal Investigator: Bianca Weinstock-Guttman, MD Jacob's Neurological Institute

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Responsible Party: Robert Zivadinov, MD, PhD, BNAC Director, University at Buffalo
ClinicalTrials.gov Identifier: NCT02775110     History of Changes
Other Study ID Numbers: USTYS0910017/JNI-2010-31
First Posted: May 17, 2016    Key Record Dates
Last Update Posted: May 17, 2016
Last Verified: May 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Multiple Sclerosis
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Natalizumab
Immunologic Factors
Physiological Effects of Drugs