RELAPSING REMITTING MULTIPLE SCLEROSISNCT02833714
Teriflunomide's Therapeutic Mechanisms of Action in Patients With Relapsing Remitting Multiple Sclerosis.
An observational study of RELAPSING REMITTING MULTIPLE SCLEROSIS, run by University of North Carolina, Chapel Hill at 1 site in United States.
Trial summary
The purpose of this research is to characterize the effect of teriflunomide on the activation of B-cells, as well as its capacity to modify B-cell cytokine secretion. The in-vitro identified effects of teriflunomide on the expression of B-cell activation markers, costimulatory and antigen presenting molecules, as well… Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- RELAPSING REMITTING MULTIPLE SCLEROSIS
- How many people
- 26 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2016to 21 Dec 2016
- Phase
- Observational
- Are there results?
- None posted in the registry
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 18 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Study population: Neurology/MS clinic: patients with Relapsing Remitting MS "Treatment naïve Relapsing Remitting MS patients will be recruited to provide samples for the in vitro tests. In addition, Relapsing Remitting MS patients who are already receiving treatment with teriflunomide as a part of their routine care will be recruited to obtain blood samples for the in vivo testing."
Who may be able to join
- confirmed diagnosis of RRMS according to McDonald's diagnostic criteria,
- age 18-55,
- an extended disability status score (EDSS) of 1.5-5.5.
Who cannot join
- Previous treatment with DMT.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of North Carolina
Chapel Hill, North Carolina, 27599
About this study
Official title: Characterization of Teriflunomide's Therapeutic Mechanisms of Action in Patients With Relapsing Remitting Multiple Sclerosis.
The purpose of this research is to characterize the effect of teriflunomide on the activation of B-cells, as well as its capacity to modify B-cell cytokine secretion. The in-vitro identified effects of teriflunomide on the expression of B-cell activation markers, costimulatory and antigen presenting molecules, as well as on cytokine secretion, will then be confirmed in a cohort of Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with this medication.
- Conditions
- RELAPSING REMITTING MULTIPLE SCLEROSIS
- Medical subject headings
- Multiple Sclerosis, Relapsing-Remitting
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Inhibition of activated/memory B-cells derived from RRMS patients.
Measured: 1 year
Secondary outcomes (3)
Change in Cytokine Secretion Profile of T-cells stimulated by teriflunomide treatment
Measured: 1 year
Measure the effect of oral teriflunomide on the cytokine secretion as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Measured: 1 year
Measure the effect of oral teriflunomide on the B cell activation as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2016 (estimated)
- Study startJan 2016
- Primary completion21 Dec 2016
- Study completion21 Dec 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (20)Papers the sponsor has linked to this study.
- Other trials for RELAPSING REMITTING MULTIPLE SCLEROSISStudies of the same condition, open and under way.
- More trials run by University of North Carolina, Chapel HillThe sponsor's other registered studies.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of North Carolina, Chapel Hill
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Silva MarkovicPlese, MD, Principal investigator, Universtiy of North Carolina at Chapel Hill
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02833714
- Sponsor's protocol ID
- 14-2877
- Status last verified
- Sep 2017
- First submitted
- 21 Jun 2016
- Last updated
- 15 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6;365(14):1293-303. doi: 10.1056/NEJMoa1014656.
PubMed 21991951Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.
PubMed 22622860Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6.
PubMed 9666414Li L, Liu J, Delohery T, Zhang D, Arendt C, Jones C. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J Neuroimmunol. 2013 Dec 15;265(1-2):82-90. doi: 10.1016/j.jneuroim.2013.10.003. Epub 2013 Oct 12.
PubMed 24182769Claussen MC, Korn T. Immune mechanisms of new therapeutic strategies in MS: teriflunomide. Clin Immunol. 2012 Jan;142(1):49-56. doi: 10.1016/j.clim.2011.02.011. Epub 2011 Mar 1.
PubMed 21367665Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol. 1999 Feb 15;162(4):2095-102.
PubMed 9973483Prineas JW, Wright RG. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest. 1978 Apr;38(4):409-21.
PubMed 205724Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.
PubMed 18272891Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, Calabresi PA, Waubant E, Hauser SL, Zhang J, Smith CH. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol. 2010 Apr;67(4):452-61. doi: 10.1002/ana.21939.
PubMed 20437580Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.
PubMed 23897062Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998 Oct 15;161(8):3912-8.
PubMed 9780157Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol. 2006 Oct 1;177(7):4481-7. doi: 10.4049/jimmunol.177.7.4481.
PubMed 16982884Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J, Oukka M, Strom TB, Rothstein TL. Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells. Eur J Immunol. 2007 Sep;37(9):2400-4. doi: 10.1002/eji.200737296.
PubMed 17683116Sellam J, Rouanet S, Hendel-Chavez H, Abbed K, Sibilia J, Tebib J, Le Loet X, Combe B, Dougados M, Mariette X, Taoufik Y. Blood memory B cells are disturbed and predict the response to rituximab in patients with rheumatoid arthritis. Arthritis Rheum. 2011 Dec;63(12):3692-701. doi: 10.1002/art.30599.
PubMed 22127692Ramgolam VS, Sha Y, Marcus KL, Choudhary N, Troiani L, Chopra M, Markovic-Plese S. B cells as a therapeutic target for IFN-beta in relapsing-remitting multiple sclerosis. J Immunol. 2011 Apr 1;186(7):4518-26. doi: 10.4049/jimmunol.1000271. Epub 2011 Mar 2.
PubMed 21368231
Study at a glance
From the registry record, last updated by the sponsor on 15 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of Teriflunomide's Therapeutic Mechanisms of Action in Patients With Relapsing Remitting Multiple Sclerosis.
- ClinicalTrials.gov ID
- NCT02833714
- Acronym / sponsor ID
- 14-2877
- Conditions
- RELAPSING REMITTING MULTIPLE SCLEROSIS
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 26 participants (actual)
- Lead sponsor
- University of North Carolina, Chapel HillUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- Jan 2016 (actual)
- Primary completion
- 21 Dec 2016 (actual)
- Study completion
- 21 Dec 2016 (actual)
- First posted
- 14 Jul 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research is to characterize the effect of teriflunomide on the activation of B-cells, as well as its capacity to modify B-cell cytokine secretion. The in-vitro identified effects of teriflunomide on the expression of B-cell activation markers, costimulatory and antigen presenting molecules, as well as on cytokine secretion, will then be confirmed in a cohort of Relapsing Remitting Multiple Sclerosis (RRMS) patients treated with this medication.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
- Study population
- Neurology/MS clinic: patients with Relapsing Remitting MS "Treatment naïve Relapsing Remitting MS patients will be recruited to provide samples for the in vitro tests. In addition, Relapsing Remitting MS patients who are already receiving treatment with teriflunomide as a part of their routine care will be recruited to obtain blood samples for the in vivo testing."
Key inclusion criteria (3 listed)
- confirmed diagnosis of RRMS according to McDonald's diagnostic criteria,
- age 18-55,
- an extended disability status score (EDSS) of 1.5-5.5.
Key exclusion criteria (1 listed)
- Previous treatment with DMT.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Percent Inhibition of activated/memory B-cells derived from RRMS patients.
Time frame: 1 year
3 secondary outcomes
Change in Cytokine Secretion Profile of T-cells stimulated by teriflunomide treatment
Time frame: 1 year
Measure the effect of oral teriflunomide on the cytokine secretion as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Time frame: 1 year
Measure the effect of oral teriflunomide on the B cell activation as measured in the ex-vivo obtained longitudinal samples from the treated patients.
Time frame: 1 year
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Sep 2017.
- Results publication: PubMed 21991951O'Connor P, Wolinsky JS, Confavreux C, Comi G, Kappos L, Olsson TP, Benzerdjeb H, Truffinet P, Wang L, Miller A, Freedman MS; TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011 Oct 6;365(14):1293-303. doi: 10.1056/NEJMoa1014656.
- Results publication: PubMed 22622860Freedman MS, Wolinsky JS, Wamil B, Confavreux C, Comi G, Kappos L, Olsson TP, Miller A, Benzerdjeb H, Li H, Simonson C, O'Connor PW; Teriflunomide Multiple Sclerosis Trial Group and the MRI Analysis Center. Teriflunomide added to interferon-beta in relapsing multiple sclerosis: a randomized phase II trial. Neurology. 2012 Jun 5;78(23):1877-85. doi: 10.1212/WNL.0b013e318258f7d4. Epub 2012 May 23.
- Results publication: PubMed 9666414Fox RI. Mechanism of action of leflunomide in rheumatoid arthritis. J Rheumatol Suppl. 1998 Jul;53:20-6.
- Results publication: PubMed 24182769Li L, Liu J, Delohery T, Zhang D, Arendt C, Jones C. The effects of teriflunomide on lymphocyte subpopulations in human peripheral blood mononuclear cells in vitro. J Neuroimmunol. 2013 Dec 15;265(1-2):82-90. doi: 10.1016/j.jneuroim.2013.10.003. Epub 2013 Oct 12.
- Results publication: PubMed 21367665Claussen MC, Korn T. Immune mechanisms of new therapeutic strategies in MS: teriflunomide. Clin Immunol. 2012 Jan;142(1):49-56. doi: 10.1016/j.clim.2011.02.011. Epub 2011 Mar 1.
- Results publication: PubMed 9973483Manna SK, Aggarwal BB. Immunosuppressive leflunomide metabolite (A77 1726) blocks TNF-dependent nuclear factor-kappa B activation and gene expression. J Immunol. 1999 Feb 15;162(4):2095-102.
- Results publication: PubMed 205724Prineas JW, Wright RG. Macrophages, lymphocytes, and plasma cells in the perivascular compartment in chronic multiple sclerosis. Lab Invest. 1978 Apr;38(4):409-21.
- Results publication: PubMed 18272891Hauser SL, Waubant E, Arnold DL, Vollmer T, Antel J, Fox RJ, Bar-Or A, Panzara M, Sarkar N, Agarwal S, Langer-Gould A, Smith CH; HERMES Trial Group. B-cell depletion with rituximab in relapsing-remitting multiple sclerosis. N Engl J Med. 2008 Feb 14;358(7):676-88. doi: 10.1056/NEJMoa0706383.
- Results publication: PubMed 20437580Bar-Or A, Fawaz L, Fan B, Darlington PJ, Rieger A, Ghorayeb C, Calabresi PA, Waubant E, Hauser SL, Zhang J, Smith CH. Abnormal B-cell cytokine responses a trigger of T-cell-mediated disease in MS? Ann Neurol. 2010 Apr;67(4):452-61. doi: 10.1002/ana.21939.
- Results publication: PubMed 23897062Kim SH, Huh SY, Lee SJ, Joung A, Kim HJ. A 5-year follow-up of rituximab treatment in patients with neuromyelitis optica spectrum disorder. JAMA Neurol. 2013 Sep 1;70(9):1110-7. doi: 10.1001/jamaneurol.2013.3071.
- Results publication: PubMed 9780157Serreze DV, Fleming SA, Chapman HD, Richard SD, Leiter EH, Tisch RM. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998 Oct 15;161(8):3912-8.
- Results publication: PubMed 16982884Yan J, Harvey BP, Gee RJ, Shlomchik MJ, Mamula MJ. B cells drive early T cell autoimmunity in vivo prior to dendritic cell-mediated autoantigen presentation. J Immunol. 2006 Oct 1;177(7):4481-7. doi: 10.4049/jimmunol.177.7.4481.
- Individual participant dataSharing planned: Undecided
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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.
Silva MarkovicPlese, MD principal investigator
Universtiy of North Carolina at Chapel Hill
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of RELAPSING REMITTING MULTIPLE SCLEROSIS, run by University of North Carolina, Chapel Hill at 1 site 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 3 inclusion and 1 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: stopped early, as of the sponsor's last update on 15 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
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?
Percent Inhibition of activated/memory B-cells derived from RRMS patients. (time frame: 1 year). 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 NCT02833714, which also lists 20 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 15 Sep 2017.