Natalizumab Temporary Discontinuation Study

NCT02775110 | Completed Phase 4

• 1 other identifier: USTYS0910017/JNI-2010-31
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

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.

Conditions

Multiple Sclerosis

Outcome Measures

Primary Outcomes (5)

• 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 Outcomes (2)

• Number of clinical relapses

  Either baseline (immediate discontinuation group) or 6 months (taper-off group)

• Expanded Disability Status Scale (EDSS) score

  Either baseline (immediate discontinuation group) or 6 months (taper-off group)

Study Arms (2)

Immediate Discontinuation Group

ACTIVE COMPARATOR

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

Taper-off Group

EXPERIMENTAL

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

Interventions

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).

Immediate Discontinuation Group; Taper-off Group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University at Buffalo: lead

Study Sites (2)

Buffalo Neuroimaging Analysis Center

Buffalo, New York, 14203, United States

Location

Jacobs Neurological Institute

Buffalo, New York, 14203, United States

Location

MeSH Terms

Conditions

Multiple Sclerosis

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Study Officials

• Bianca Weinstock-Guttman, MD

  Jacob's Neurological Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: BNAC Director

Study Record Dates

• First Submitted: December 29, 2015
• First Posted: May 17, 2016
• Study Start: November 1, 2012
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 17, 2016

Record last verified: 2016-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)