Natalizumab Temporary Discontinuation Study (NaTDS)

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Other: Natalizumab 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.

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • Buffalo, New York, United States, 14203
      • Buffalo Neuroimaging Analysis Center
    • Buffalo, New York, United States, 14203
      • Jacobs Neurological Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	Up to 1 year follow-up
Saturation percentage of α4β1integrin receptors on the surface of lymphocytes		12 months
Number gadolinium-enhancing lesions	Number of gadolinium-enhancing lesions	Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Absolute changes in gadolinium-enhancing and T2-weighted lesion volume between timepoints	Absolute changes in gadolinium-enhancing and T2-weighted lesion volume	Change between baseline-6 months, 6 months-12 months, and baseline-12 months
Sum of new and enlarging T2-weighted lesions	Sum of new and enlarging lesions as seen on T2-weighted images	Change between baseline-6 months, 6 months-12 months, and baseline-12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	Either baseline (immediate discontinuation group) or 6 months (taper-off group)
Expanded Disability Status Scale (EDSS) score	Expanded disability status scale score	Either baseline (immediate discontinuation group) or 6 months (taper-off group)

Collaborators and Investigators

• Sponsor: University at Buffalo
• Investigators: Principal Investigator: Bianca Weinstock-Guttman, MD, Jacob's Neurological Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): March 1, 2014

Study Registration Dates

• First Submitted: December 29, 2015
• First Submitted That Met QC Criteria: May 13, 2016
• First Posted (Estimate): May 17, 2016

Study Record Updates

• Last Update Posted (Estimate): May 17, 2016
• Last Update Submitted That Met QC Criteria: May 13, 2016
• Last Verified: May 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Multiple Sclerosis; Physiological Effects of Drugs; Immunologic Factors; Natalizumab
• Other Study ID Numbers: USTYS0910017/JNI-2010-31

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO