Multiple SclerosisPhase 4NCT01970410
MAIN STUDY: SWITCH SUB-STUDY: SWITCH-JCV
A Phase 4 study testing teriflunomide in people with Multiple Sclerosis, run by Providence Health & Services at 3 sites in United States.
Trial summary
MAIN STUDY: 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. Read more about this study
- Who is it for?
- Ages 21 to 60 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- teriflunomide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 55 participants
- Where
- 3 sitesUnited States
- Study dates
- Oct 2013to 14 Feb 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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 cerebrospinal fluid (CSF) for PML.
- No evidence of significant cognitive limitation or psychiatric disorder.
- Expanded Disability Status Scale (EDSS) of 1.0 to 6.0 inclusive.
Who cannot join
- 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.
Show all 31Show fewer
- 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:
- Hypoproteinemia with serum albumin < 3.0g/dl.
- Serum creatinine >133umol/L (or >1.5 mg/dl)
- Hematocrit <24% and/or
- Absolute white blood cell count < 4,000 cells/mm3 (µl) and/or
- Platelet Count <150,000 cells/mm3 (µl) and /or
- Absolute neutrophil < 1,500 cells/mm3 (µl)
- Liver function impairment or persisting elevations of serum glutamate pyruvate transaminase (SGPT)/ Alanine transaminase (ALT), serum glutamate oxaloacetate transaminase (SGOT)/ aspartate aminotransferase (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
- SUB-STUDY
- 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.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Multiple Sclerosis Center of Northeastern New York
Latham, New York, 12110
Phoenix Neurological Associates, Ltd
Phoenix, Arizona, 85018
Providence Multiple Sclerosis Center
Portland, Oregon, 97225
About this study
Official title: MAIN STUDY: Switching Relapsing Multiple Sclerosis Patients Treated With Natalizumab at Risk for Progressive Multifocal Leukoencephalopathy to Teriflunomide: Is This Safe and Effective? SUB-STUDY: Analysis of JCV Antibody Index in MS Patients Treated With Teriflunomide
MAIN STUDY: 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.
SUB-STUDY: To study the number of patients experiencing a reduction in the anti-JCV antibody Index value in patients who had received at least one dose of teriflunomide during participation in the SWITCH protocol (main study).
Read the detailed description
MAIN STUDY: Teriflunomide (TFM) 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 "enhancing" (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.
SUB-STUDY: John Cunningham virus (JCV) is the responsible organism for the development of progressive multifocal encephalopathy (PML). Multiple sclerosis (MS) patients treated with natalizumab (NTZ), who have evidence of exposure to JCV have a significantly elevated risk, as high as 12/1000 patients, of developing PML, necessitating the elective transition of patients off NTZ.
JCV is a member of the polyoma virus family, and closely related to BK virus. BK virus has been found to be a significant threat to destroy transplanted kidneys and there is growing evidence that treatment with leflunomide, the pro-drug of teriflunomide (TFM) clears BKV from the kidney.
Main study assessed the clinical efficacy of TFM in MS patients transitioned off NTZ solely because they have evidence of exposure to JCV, as determined by the presence of serum anti-JCV immunoglobulin G (IgG). Previous work by other investigators has demonstrated a close correlation between positive anti-JCV antibody titers and the presence of active JCV infection.
There is evidence that JCV is closely related to its fellow polyoma virus BKV, and that BKV is cleared by treatment with the TFM pro-drug leflunomide, we propose to determine if treatment of the JCV antibody positive patients currently enrolled in the approved protocol results in reduction in, or reversion to negative, of the anti-JCV antibody titer as measured by the JCV antibody Index, a commercially available assay which is used internationally as the standard for evidence of JCV exposure in NTZ-treated patients.
- Conditions
- Multiple Sclerosis
- Being tested
- teriflunomide
- Keywords
- teriflunomide, natalizumab, relapsing multiple sclerosis
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
teriflunomideDrug
Also called Aubagio
14 mg oral teriflunomide daily
| Study group | Role | What they receive |
|---|---|---|
| Teriflunomide | Experimental | Teriflunomide 14 mg oral teriflunomide daily Receives: Drug: teriflunomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
MAIN STUDY: Number of Participants Relapse Free at 24 Months
Number of patients relapses free by month 24.
Measured: 24 months
Secondary outcomes (3)
MAIN STUDY: Time to Return of Radiological Evidence of Multiple Sclerosis Activity With New Gadolinium "Enhancing" (Gd+) Lesions on Cranial MRI.
Mean time to first Gadolinium "enhancing" (GAD+) lesion in months.
Measured: 24 months
MAIN STUDY: Expanded Disability Status Scale (EDSS) Sustained Progression for 3 Months as Measured by at Least 0.5 Increase From Baseline or 1 in Any EDSS Set Score
Mean time to 3-month sustained disability worsening (SDW) in months. SDW is defined as an increase of ≥ 1 point for patients with EDSS of 1.0-5.0, and ≥ 0.5 points for patients with an EDSS of 5.5-6.0, sustained for 3 months. Patients with ≥ 1 point increase in EDSS in whom a second measure was not obtained 3 months later were not included as SDW.
Measured: 24 months
MAIN STUDY: Mean Time to New T2 or Enlarging T2 Hyperintensities on Monthly Sentinel Brain MRIs
Mean time of new T2 or enlarging T2 Lesions
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2013 (estimated)
- Study startOct 2013
- Primary completion30 Apr 2021
- Study completion14 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Providence Health & Services
- Sponsor type
- University, hospital or other
- Collaborators
- Multiple Sclerosis Center of Northeastern New York
- Responsible party
- Sponsor
- Investigators
- Keith R Edwards, MD, Study director, Multiple Sclerosis Center of Northeastern New YorkStanley Cohan, MD, Ph. D, Principal investigator, Providence Multiple Sclerosis Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01970410
- Sponsor's protocol ID
- SWITCH-001
- Status last verified
- Jan 2023
- First submitted
- 22 Oct 2013
- Last updated
- 30 Jan 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. 2011 Aug;124(2):75-84. doi: 10.1111/j.1600-0404.2010.01444.x. Epub 2010 Sep 29.
PubMed 20880295Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ. Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol. 1999 Dec;93(3):198-208. doi: 10.1006/clim.1999.4777.
PubMed 10600330Ruckemann K, Fairbanks LD, Carrey EA, Hawrylowicz CM, Richards DF, Kirschbaum B, Simmonds HA. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem. 1998 Aug 21;273(34):21682-91. doi: 10.1074/jbc.273.34.21682.
PubMed 9705303Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.
PubMed 16510744Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, Pace A, Cheung A, Chen LL, Berman M, Zein F, Wilson E, Yednock T, Sandrock A, Goelz SE, Subramanyam M. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010 Sep;68(3):295-303. doi: 10.1002/ana.22128.
PubMed 20737510Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012 May 17;366(20):1870-80. doi: 10.1056/NEJMoa1107829.
PubMed 22591293Miravalle A, Jensen R, Kinkel RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. 2011 Feb;68(2):186-91. doi: 10.1001/archneurol.2010.257. Epub 2010 Oct 11.
PubMed 20937940Stuve O, Cravens PD, Frohman EM, Phillips JT, Remington GM, von Geldern G, Cepok S, Singh MP, Tervaert JW, De Baets M, MacManus D, Miller DH, Radu EW, Cameron EM, Monson NL, Zhang S, Kim R, Hemmer B, Racke MK. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology. 2009 Feb 3;72(5):396-401. doi: 10.1212/01.wnl.0000327341.89587.76. Epub 2008 Nov 5.
PubMed 18987352Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
PubMed 6685237Cohan SL, Edwards K, Lucas L, Gervasi-Follmar T, O'Connor J, Siuta J, Kamath V, Garten L, Chen C, Thomas J, Smoot K, Kresa-Reahl K, Spinelli KJ. Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy. Mult Scler J Exp Transl Clin. 2019 Jan 16;5(1):2055217318824618. doi: 10.1177/2055217318824618. eCollection 2019 Jan-Mar.
PubMed 30729028Cohan S, Gervasi-Follmar T, Kamath A, Kamath V, Chen C, Smoot K, Baraban E, Edwards K. The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide. Mult Scler J Exp Transl Clin. 2021 Dec 16;7(4):20552173211066588. doi: 10.1177/20552173211066588. eCollection 2021 Oct.
PubMed 34950502
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- MAIN STUDY: Switching Relapsing Multiple Sclerosis Patients Treated With Natalizumab at Risk for Progressive Multifocal Leukoencephalopathy to Teriflunomide: Is This Safe and Effective? SUB-STUDY: Analysis of JCV Antibody Index in MS Patients Treated With Teriflunomide
- ClinicalTrials.gov ID
- NCT01970410
- Acronym / sponsor ID
- SWITCH-001
- Conditions
- Multiple Sclerosis
- Keywords
- teriflunomide, natalizumab, relapsing multiple sclerosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Providence Health & ServicesUniversity, hospital or other
- Collaborators
- Multiple Sclerosis Center of Northeastern New York
- Study start
- Oct 2013
- Primary completion
- 30 Apr 2021 (actual)
- Study completion
- 14 Feb 2022 (actual)
- First posted
- 28 Oct 2013 (estimated)
- Results
- Posted 20 Oct 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
MAIN STUDY: 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.
SUB-STUDY: To study the number of patients experiencing a reduction in the anti-JCV antibody Index value in patients who had received at least one dose of teriflunomide during participation in the SWITCH protocol (main study).
Detailed description
MAIN STUDY: Teriflunomide (TFM) 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 "enhancing" (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.
SUB-STUDY: John Cunningham virus (JCV) is the responsible organism for the development of progressive multifocal encephalopathy (PML). Multiple sclerosis (MS) patients treated with natalizumab (NTZ), who have evidence of exposure to JCV have a significantly elevated risk, as high as 12/1000 patients, of developing PML, necessitating the elective transition of patients off NTZ.
JCV is a member of the polyoma virus family, and closely related to BK virus. BK virus has been found to be a significant threat to destroy transplanted kidneys and there is growing evidence that treatment with leflunomide, the pro-drug of teriflunomide (TFM) clears BKV from the kidney.
Main study assessed the clinical efficacy of TFM in MS patients transitioned off NTZ solely because they have evidence of exposure to JCV, as determined by the presence of serum anti-JCV immunoglobulin G (IgG). Previous work by other investigators has demonstrated a close correlation between positive anti-JCV antibody titers and the presence of active JCV infection.
There is evidence that JCV is closely related to its fellow polyoma virus BKV, and that BKV is cleared by treatment with the TFM pro-drug leflunomide, we propose to determine if treatment of the JCV antibody positive patients currently enrolled in the approved protocol results in reduction in, or reversion to negative, of the anti-JCV antibody titer as measured by the JCV antibody Index, a commercially available assay which is used internationally as the standard for evidence of JCV exposure in NTZ-treated patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Teriflunomide | Experimental | Drug: teriflunomideTeriflunomide 14 mg oral teriflunomide daily |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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 cerebrospinal fluid (CSF) for PML.
Key exclusion criteria (31 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| teriflunomideAlso: Aubagio14 mg oral teriflunomide daily | Drug | Teriflunomide |
Primary outcome
MAIN STUDY: Number of Participants Relapse Free at 24 Months
Time frame: 24 months
Number of patients relapses free by month 24.
3 secondary outcomes
MAIN STUDY: Time to Return of Radiological Evidence of Multiple Sclerosis Activity With New Gadolinium "Enhancing" (Gd+) Lesions on Cranial MRI.
Time frame: 24 months
MAIN STUDY: Expanded Disability Status Scale (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: 24 months
MAIN STUDY: Mean Time to New T2 or Enlarging T2 Hyperintensities on Monthly Sentinel Brain MRIs
Time frame: 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20880295Gold R, Wolinsky JS. Pathophysiology of multiple sclerosis and the place of teriflunomide. Acta Neurol Scand. 2011 Aug;124(2):75-84. doi: 10.1111/j.1600-0404.2010.01444.x. Epub 2010 Sep 29.
- Background: PubMed 10600330Fox RI, Herrmann ML, Frangou CG, Wahl GM, Morris RE, Strand V, Kirschbaum BJ. Mechanism of action for leflunomide in rheumatoid arthritis. Clin Immunol. 1999 Dec;93(3):198-208. doi: 10.1006/clim.1999.4777.
- Background: PubMed 9705303Ruckemann K, Fairbanks LD, Carrey EA, Hawrylowicz CM, Richards DF, Kirschbaum B, Simmonds HA. Leflunomide inhibits pyrimidine de novo synthesis in mitogen-stimulated T-lymphocytes from healthy humans. J Biol Chem. 1998 Aug 21;273(34):21682-91. doi: 10.1074/jbc.273.34.21682.
- Background: PubMed 16510744Polman CH, O'Connor PW, Havrdova E, Hutchinson M, Kappos L, Miller DH, Phillips JT, Lublin FD, Giovannoni G, Wajgt A, Toal M, Lynn F, Panzara MA, Sandrock AW; AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006 Mar 2;354(9):899-910. doi: 10.1056/NEJMoa044397.
- Background: PubMed 20737510Gorelik L, Lerner M, Bixler S, Crossman M, Schlain B, Simon K, Pace A, Cheung A, Chen LL, Berman M, Zein F, Wilson E, Yednock T, Sandrock A, Goelz SE, Subramanyam M. Anti-JC virus antibodies: implications for PML risk stratification. Ann Neurol. 2010 Sep;68(3):295-303. doi: 10.1002/ana.22128.
- Background: PubMed 22591293Bloomgren G, Richman S, Hotermans C, Subramanyam M, Goelz S, Natarajan A, Lee S, Plavina T, Scanlon JV, Sandrock A, Bozic C. Risk of natalizumab-associated progressive multifocal leukoencephalopathy. N Engl J Med. 2012 May 17;366(20):1870-80. doi: 10.1056/NEJMoa1107829.
- Background: PubMed 20937940Miravalle A, Jensen R, Kinkel RP. Immune reconstitution inflammatory syndrome in patients with multiple sclerosis following cessation of natalizumab therapy. Arch Neurol. 2011 Feb;68(2):186-91. doi: 10.1001/archneurol.2010.257. Epub 2010 Oct 11.
- Background: PubMed 18987352Stuve O, Cravens PD, Frohman EM, Phillips JT, Remington GM, von Geldern G, Cepok S, Singh MP, Tervaert JW, De Baets M, MacManus D, Miller DH, Radu EW, Cameron EM, Monson NL, Zhang S, Kim R, Hemmer B, Racke MK. Immunologic, clinical, and radiologic status 14 months after cessation of natalizumab therapy. Neurology. 2009 Feb 3;72(5):396-401. doi: 10.1212/01.wnl.0000327341.89587.76. Epub 2008 Nov 5.
- Background: PubMed 6685237Kurtzke JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology. 1983 Nov;33(11):1444-52. doi: 10.1212/wnl.33.11.1444.
- Results publication: PubMed 30729028Cohan SL, Edwards K, Lucas L, Gervasi-Follmar T, O'Connor J, Siuta J, Kamath V, Garten L, Chen C, Thomas J, Smoot K, Kresa-Reahl K, Spinelli KJ. Reducing return of disease activity in patients with relapsing multiple sclerosis transitioned from natalizumab to teriflunomide: 12-month interim results of teriflunomide therapy. Mult Scler J Exp Transl Clin. 2019 Jan 16;5(1):2055217318824618. doi: 10.1177/2055217318824618. eCollection 2019 Jan-Mar.
- Results publication: PubMed 34950502Cohan S, Gervasi-Follmar T, Kamath A, Kamath V, Chen C, Smoot K, Baraban E, Edwards K. The results of a 24-month controlled, prospective study of relapsing multiple sclerosis patients at risk for progressive multifocal encephalopathy, who switched from prolonged use of natalizumab to teriflunomide. Mult Scler J Exp Transl Clin. 2021 Dec 16;7(4):20552173211066588. doi: 10.1177/20552173211066588. eCollection 2021 Oct.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Keith R Edwards, MD study director
Multiple Sclerosis Center of Northeastern New York
Stanley Cohan, MD, Ph. D principal investigator
Providence Multiple Sclerosis Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing teriflunomide in people with Multiple Sclerosis, run by Providence Health & Services at 3 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 31 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Oct 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
MAIN STUDY: Number of Participants Relapse Free at 24 Months (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01970410, which also lists 11 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2023.