Clinical Trial: Safety and Effectiveness of Switching Relapsing MS Patients Treated With Natalizumab at Risk for PML to Teriflunomide

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Switching Relapsing Multiple Sclerosis Patients Treated With Natalizumab at Risk for Progressive Multifocal Leukoencephalopathy to Teriflunomide: Is This Safe and Effectiv

Brief Summary: The purpose of this study is to determine if teriflunomide will be safe and effective to prevent relapses in patients with relapsing types of MS when switching from natalizumab to teriflunomide in patients at risk for PML. This is a two center interventional study of patients who have had 12 or more continuous infusions of natalizumab , who are anti-JCV-ab positive, and who had been free of clinical relapses during prior 12 months of natalizumab therapy who will be switching to teriflunomide.

Detailed Summary:

Teriflunomide is the primary metabolite of leflunomide, which is marketed worldwide for the treatment of rheumatoid arthritis. Teriflunomide inhibits dihydroorotate dehydrogenase( DHODH), the forth enzyme in the de novo synthesis pathway of pyrimidines.Activated T-lymphocytes utilize both the de novo pyrimidine and salvage pathways of pyrimidines ribonucleotide synthesis.After mitogen stimulation, teriflunomide inhibits in vitro T cell proliferation, DNA and RNA synthesis and expression of cell surface and nuclear antigens that are directly involved in T-cell activation and proliferation.

Natalizumab (NTZ) is a FDA approved treatment for relapsing-forms of multiple sclerosis (MS) with pivotal studies showing an annualized relapse-rate (ARR) reduction of 68%, a reduction of new gadolinium (Gd+) lesions by 92% and a reduction of disability of 42% compared to placebo.NTZ is highly effective in controlling MS but the risk of developing progressive multifocal leukoencephalopathy (PML) increases with the duration of the use of natalizumab. It can have a serious and life threatening complication in about 1 in 500 to 1 in 250 patients who have had more that 18 infusions due PML and who have a detected antibody (Ab) for the JC virus. The risk of PML is much greater in patients who have had prior immunosuppressive (IS) treatment. The combination of detected anti-JCV Ab , duration of NTZ treatment of greater than 24 months and prior IS increases the risk of development PML to an incidence of 11 per 1000 treated patients. So there is a need to have an alternative MS disease modifying treatment (DMT) to use for patients at risk to develop PML from NTZ treatment that might be sufficiently effective for MS so as not to have the patients' MS worsen while lowering or eliminating the risk of PML.


Sponsor: Multiple Sclerosis Center of Northeastern New York

Current Primary Outcome: Proportion of patients relapse free at 12 months [ Time Frame: 12 months ]

Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to return of radiological evidence of MS activity with new Gd+ lesions on cranial MRI. [ Time Frame: 12 months ]
  • EDSS sustained progression for 3 months as measured by at least 0.5 increase from baseline or 1 in any EDSS set score [ Time Frame: 12 months ]
  • Number of new T2 or enlarging T2 hyperintensities on monthly sentinel brain MRIs [ Time Frame: 12 months ]


Original Secondary Outcome: Same as current

Information By: Multiple Sclerosis Center of Northeastern New York

Dates:
Date Received: October 22, 2013
Date Started: October 2013
Date Completion: December 2017
Last Updated: October 24, 2016
Last Verified: October 2016