Try the modernized beta website. Learn more about the modernization effort.
Working… Menu

Sub-Study: Analysis of JCV Antibody Index in MS Patients Treated With Teriflunomide - SWITCH-JCV

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01970410
Recruitment Status : Active, not recruiting
First Posted : October 28, 2013
Last Update Posted : January 12, 2022
Multiple Sclerosis Center of Northeastern New York
Information provided by (Responsible Party):
Providence Health & Services

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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: teriflunomide Phase 4

Detailed Description:

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 41 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Switching Relapsing Multiple Sclerosis Patients Treated With Natalizumab at Risk for Progressive Multifocal Leukoencephalopathy to Teriflunomide: Is This Safe and Effective? (Sub-study: SWITCH-JCV)
Study Start Date : October 2013
Actual Primary Completion Date : April 30, 2021
Estimated Study Completion Date : December 1, 2022

Arm Intervention/treatment
Experimental: Teriflunomide
Teriflunomide 14 mg oral teriflunomide daily
Drug: teriflunomide
14 mg oral teriflunomide daily
Other Name: Aubagio

Primary Outcome Measures :
  1. Proportion of patients relapse free at 12 months [ Time Frame: 12 months ]

Secondary Outcome Measures :
  1. Time to return of radiological evidence of MS activity with new Gd+ lesions on cranial MRI. [ Time Frame: 12 months ]
  2. 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 ]
  3. Number of new T2 or enlarging T2 hyperintensities on monthly sentinel brain MRIs [ Time Frame: 12 months ]
  4. anti-JCV antibody status [ Time Frame: 30 days ]
    Number of patients with a reduction in the anti-JCV antibody Index value

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   21 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Male and female patients, age 21 to 60 with relapsing forms of MS, treated with natalizumab for 12 consecutive months or longer with anti-JCV Ab positive during that time period.
  • Able to understand and sign Informed Consent Document.
  • Stable disease during treatment with natalizumab. No clinical relapses for at least 12 months.
  • Stable MRI on follow-up MRI scans for prior 12 months without evidence of new or enlarging T-2 hyperintensities or Gd+ lesions.
  • No clinical evidence by imaging or CSF for PML.
  • No evidence of significant cognitive limitation or psychiatric disorder.
  • EDSS of 1.0 to 6.0 inclusive.

Exclusion Criteria:

  • Any mental condition of such that patient is unable to understand the nature, scope and possible consequences of the study.
  • Patients that are known HIV positive.
  • Patients with a known history of hepatitis.
  • Known history of active tuberculosis not adequately treated, or a positive ppd skin test or positive quantiferon gold.
  • Any persistent or severe infection.
  • Any malignancy within 5 years, except for Basal or Squamous cell skin lesions, which have been surgically excised, with no evidence of metastasis.
  • Clinically relevant or unstable cardiovascular, neurological (i.e. progressive weakness, increasing hypesthesia), endocrine, or other major systemic diseases.
  • History of drug or alcohol abuse within the past year.
  • Any significant depression or psychiatric disease (BDI II greater than 25) within the past year.
  • Any significant lab abnormality as deemed by the investigator including but not limited to the following:

    1. Hypoproteinemia with serum albumin < 3.0g/dl.
    2. Serum creatinine >133umol/L (or >1.5 mg/dl)
    3. Hematocrit <24% and/or
    4. Absolute white blood cell count < 4,000 cells/mm3 (µl) and/or
    5. Platelet Count <150,000 cells/mm3 (µl) and /or
    6. Absolute neutrophil < 1,500 cells/mm3 (µl)
    7. Liver function impairment or persisting elevations of SGPT/ALT, SGOT/AST, or direct bilirubin greater than 1.5 fold the upper limit of normal.
  • Any confounding illness or other diseases of the spine or bone that would impair evaluation of the patient or treatment effects.
  • Any clinical, CSF or MRI evidence for PML.
  • Prior treatment with immunosuppressive drugs except for past use of intravenous steroids to treat MS relapses.
  • Pregnant or breast feeding women.
  • Women of childbearing potential not protected by effective contraceptive method of birth control and/or are unwilling or unable to be tested for pregnancy.
  • In the conception of a child during the course of the trial.
  • Known history of hypersensitivity to teriflunomide or leflunomide.
  • Persisting elevations (confirmed by retest) of serum amylase or lipase greater than 2-fold the upper limit of normal.
  • Known history of chronic pancreatic disease or pancreatitis.
  • Prior use within 4 weeks before randomization or concomitant use of phenytoin, warfarin, tolbutamide, cholestyramine, or products containing St. John's Wort

Eligibility Criteria for JCV sub-study:

  • Must have been enrolled in the SWITCH protocol and received at least 1 dose of 14mg TFM during the study period.
  • Must be willing to sign written, informed consent for this JCV sub-study and follow protocol requirements.

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 identifier (NCT number): NCT01970410

Layout table for location information
United States, Arizona
Phoenix Neurological Associates, Ltd
Phoenix, Arizona, United States, 85018
United States, New York
Multiple Sclerosis Center of Northeastern New York
Latham, New York, United States, 12110
United States, Oregon
Providence Multiple Sclerosis Center
Portland, Oregon, United States, 97225
Sponsors and Collaborators
Providence Health & Services
Multiple Sclerosis Center of Northeastern New York
Layout table for investigator information
Study Director: Keith R Edwards, MD Multiple Sclerosis Center of Northeastern New York
Principal Investigator: Stanley Cohan, MD, Ph. D Providence Multiple Sclerosis Center
Publications of Results:

Other Publications:
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Providence Health & Services Identifier: NCT01970410    
Other Study ID Numbers: SWITCH-001
First Posted: October 28, 2013    Key Record Dates
Last Update Posted: January 12, 2022
Last Verified: January 2022
Keywords provided by Providence Health & Services:
relapsing multiple sclerosis
Additional relevant MeSH terms:
Layout table for MeSH terms
Multiple Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Immunosuppressive Agents
Immunologic Factors