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Completed

NCT Number: NCT02775110

Natalizumab Temporary Discontinuation Study

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.

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Key information

Conditions

Multiple Sclerosis Autoimmune Diseases Autoimmune Diseases of the Nervous System Demyelinating Autoimmune Diseases, CNS Demyelinating Diseases Immune System Diseases Nervous System Diseases

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Primary location

Buffalo Neuroimaging Analysis Center, Buffalo, New York, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Natalizumab discontinuation

Other

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 outcomes

  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 outcomes

  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

Sponsors and collaborators

Lead sponsor

University at Buffalo

Other

Registry information

Acronym: NaTDS

Important dates

Study start
2012
Primary completion
2014
Study completion
2014
First posted
May 17, 2016
Registry last updated
May 17, 2016

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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