Multiple SclerosisPhase 3TERISNCT03122652
Randomized, Double-blinded Study of Treatment:Teriflunomide, in Radiologically Isolated Syndrome
A Phase 3 study testing Teriflunomide 14 MG Oral Tablet [Aubagio] in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nice at 23 sites in 3 countries.
Trial summary
Multiple sclerosis (MS) is a common cause of severe neurological disability in young adults, resulting from an autoimmune interruption of both myelin and axons within the central nervous system (CNS). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Teriflunomide 14 MG Oral Tablet [Aubagio]
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 23 sitesin 3 countries
- Study dates
- 25 Sep 2017to 4 Oct 2022
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females of all ages(>18 years and <65 years) meeting 2009 RIS criteria:
- The presence of incidentally identified CNS white matter anomalies meeting the following MRI criteria:
- Ovoid, well-circumscribed, and homogeneous foci observed with or without involvement of the corpus callosum
- T2 hyperintensities measuring ≥3 mm and fulfilling Barkhof criteria (at least three out of four) for dissemination in space
- Anomalies not following a clear vascular pattern
- Structural neuroimaging abnormalities identified not explained by another disease process B. No historical accounts of remitting clinical symptoms consistent with neurological dysfunction C. The MRI anomalies do not account for clinically apparent impairments in social, occupational, or generalized area of functioning D. The MRI anomalies are not due to the direct physiological effects of substances (recreational drug use, toxic exposure) or a medical condition E. Exclusion of individuals with MRI phenotypes suggestive of leukoaraiosis or extensive white matter changes lacking clear involvement of the corpus callosum F. The CNS MRI anomalies are not better accounted for by another disease process
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- Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated ≥ 2009
- Incidental anomalies identified on MRI of the brain or spinal cord with the primary reason for the acquired MRI resulting from an evaluation of a process other than MS
- Affiliation to the social security system
- Subjects of reproductive potential are eligible only if the following applies:
- Women of childbearing potential (WOCBP):Must have a negative serum pregnancy test at Visit 1 (Screening) and negative urine pregnancy test at Visit 2 (Baseline);
- Must be agree to undertake 1 monthly urine pregnancy tests during the study and up to 6 weeks after the first of two tests showing teriflunomide plasma level <0.02 mg/L;
- Must agree to use reliable methods of contraception from Visit 1 until 6 weeks after the first oft wo tests showing teriflunomide plasma level <0.02 mg/L.
- Fertile male subjects participating in the study who are sexually active with WOCBP:
- Must agree to use condom during the treatment period and for an additional 6 weeks after the first oft wo tests showing teriflunomide plasma level <0.02 mg/L.
Who cannot join
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of summary of product characteristics (SmPC).
- Patients with severe hepatic impairment (Child-Pugh class C).
- Patients with severe immunodeficiency states, e.g. AIDS.
- Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.
- Patients with severe active infection until resolution.
- Patients with severe renal impairment undergoing dialysis.
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- Patients with severe hypoproteinaemia, e.g. in nephrotic syndrome.
- Lactating or pregnant women
- Subjects wishing to parent a child during the study
- Incomplete medical history or radiological data
- History of remitting clinical symptoms consistent with multiple sclerosis lasting > 24 hours prior to CNS imaging revealing anomalies suggestive of MS
- History of paroxysmal symptoms associated with MS (i.e. Lhermitte's or Uhthoff's phenomena)
- CNS MRI anomalies are better accounted for by another disease process
- The subject is unwilling or unable to comply with the requirements of the study protocol
- Exposure to a disease modifying therapy within the past 3 months
- Exposure to high-dose glucocorticosteroid treatment within the past 30 days
- Vulnerable subject (such as deprived from freedom) as defined in Section 1.61 of International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (GCP: Individuals whose willingness to volunteer in a clinical trial may be unduly influenced by the expectation, whether justified or not, of benefits associated with participation, or of a retaliatory response from senior members of a hierarchy in case of refusal to participate. Examples are members of a group with a hierarchical structure, such as medical, pharmacy, dental, and nursing students, subordinate hospital and laboratory personnel, employees of the pharmaceutical industry, members of the armed forces, and persons kept in detention. Other vulnerable subjects include patients with incurable diseases, persons in nursing homes, unemployed or impoverished persons, patients in emergency situations, ethnic minority groups, homeless persons, nomads, refugees, minors, and those incapable of giving consent.)
- Participation in another clinical trial of an investigational medicinal product
Trial locations and contacts
23 sites in 3 countries.
23 sites in 3 countries
France15 sites
CHU de Bordeaux
Bordeaux, 33000
CHU de Caen
Caen
CHU de Clermont-Ferrand
Clermont-Ferrand
CHU de Grenoble
Grenoble
CHRU de Lille
Lille, 59000
Hospices Civils de Lyon
Lyon, 69677
CHRU de Montpellier
Montpellier, 34000
CHU de Nantes
Nantes
CHU de Nice
Nice, 06000
CHU de Nîmes
Nîmes
APHP - Hôpital La Pitié Salpêtrière
Paris, 75013
CHU de Rennes
Rennes, 35000
CHU de Rouen
Rouen
CHU de Strasbourg
Strasbourg, 67000
CHU de Toulouse
Toulouse, 31000
Turkey (Türkiye)7 sites
Hacettepe University
Ankara
Mustafa Kemal University
Antakya
Uludag University School of Medicine
Bursa
Istanbul University
Istanbul
Ege University Medical Faculty
Izmir, 35100
Kocaeli University School of Medicine
Kocaeli
Ondokuz Mayis University, Faculty of Medicine
Samsun
About this study
Official title: Multi-center, Randomized, Double-blinded Study of Teriflunomide® in Radiologically Isolated Syndrome (RIS) The TERIS Study
Multiple sclerosis (MS) is a common cause of severe neurological disability in young adults, resulting from an autoimmune interruption of both myelin and axons within the central nervous system (CNS). The diagnosis is made by fulfilling both spatial criteria, by meeting the requisite number of lesions within the brain or spinal cord, along with criteria for time, by demonstrating a history of at least a second clinical attack or the development of a new MS lesion on MRI after the seminal neurological event. In the case of MS, healthy individuals who do not exhibit signs of neurological dysfunction commonly have brain MRI studies performed for a reason other than an evaluation for MS that reveal unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack symptomatology suggestive of MS and fulfill formal criteria for radiologically isolated syndrome (RIS), a recently described MS subtype that expands upon the phenotype of at-risk individuals for future demyelinating events. The discovery of such anomalies creates intersecting neuro-ethical, legal, social, and practical medical management quandaries and is, therefore, of both immediate and long-term clinical significance. Despite advancements in the characterization of RIS subjects, and in our understanding of risk factors for initial symptom development, the effect of treatment on such cases remain unclear.
The purpose of this investigation is to systematically study the efficacy of Teriflunomide in those individuals who possess incidental white matter anomalies within the brain and following a MRI study that is performed for a reason other than for the evaluation of MS.
Read more
RIS subjects are frequently exposed to disease modifying therapies despite the lack of scientific literature supporting the use of such treatments. Earlier treatment intervention may extend the time to the first acute or progressive clinical event resulting from CNS demyelination and reduce radiological progression. In addition, early treatment may result in more profound effects on reducing disability progression long-term.
The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination.
This study will include RIS subjects from the Europe who fulfill 2009 RIS Criteria.
- Conditions
- Multiple Sclerosis
- Being tested
- Teriflunomide 14 MG Oral Tablet [Aubagio], Placebo Oral Tablet
- Keywords
- Radiologically Isolated Syndrome
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Teriflunomide 14 MG Oral Tablet [Aubagio]Drug
1 tablet once a day
Placebo Oral TabletDrug
1 tablet once a day
| Study group | Role | What they receive |
|---|---|---|
| Terifunomide | Experimental | Not described Receives: Drug: Teriflunomide 14 MG Oral Tablet [Aubagio] |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to the first acute or progressive neurological event resulting from CNS demyelination.
Acute neurological event: The development of an acute neurological episode localized to the optic nerve, brainstem, cerebellum, spinal cord, or long sensory or motor tracts, lasting > 24 hours followed by a period of symptom improvement.
Progressive event: The onset of a clinical symptom (e.g. leg weakness) with the temporal profile revealing at least a 12-month progression of neurological deficits.
Measured: Week 96
Secondary outcomes (7)
New or enlarging T2 lesions
Number of new or enlarging T2 lesions on MRI
Measured: Week 48
New or enlarging T2 lesions
Number of new or enlarging T2 lesions on MRI
Measured: Week 96
New contrast enhancing lesions
New contrast enhancing lesions on MRI
Measured: Week 48
New contrast enhancing lesions
New contrast enhancing lesions on MRI
Measured: Week 96
New T2-lesion volumes
New T2-lesion volumes on MRI
Measured: Week 48
New T2-lesion volumes
New T2-lesion volumes on MRI
Measured: Week 96
Brain atrophy
Brain atrophy on MRI
Measured: Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2017
- Study start25 Sep 2017
- Primary completion5 Feb 2019
- Study completion4 Oct 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Responsible party
- Sponsor
- Investigators
- Christine LEBRUN-FRENAY, MD, Principal investigator, Centre Hospitalier Universitaire de Nice
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03122652
- Sponsor's protocol ID
- 14-PP-11
- Acronym
- TERIS
- Status last verified
- Mar 2023
- First submitted
- 12 Apr 2017
- Last updated
- 17 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Lebrun-Frenay C, Siva A, Sormani MP, Landes-Chateau C, Mondot L, Bovis F, Vermersch P, Papeix C, Thouvenot E, Labauge P, Durand-Dubief F, Efendi H, Le Page E, Terzi M, Derache N, Bourre B, Hoepner R, Karabudak R, De Seze J, Ciron J, Clavelou P, Wiertlewski S, Turan OF, Yucear N, Cohen M, Azevedo C, Kantarci OH, Okuda DT, Pelletier D; TERIS Study Group. Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1080-1088. doi: 10.1001/jamaneurol.2023.2815.
PubMed 37603328
Study at a glance
From the registry record, last updated by the sponsor on 17 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multi-center, Randomized, Double-blinded Study of Teriflunomide® in Radiologically Isolated Syndrome (RIS) The TERIS Study
- ClinicalTrials.gov ID
- NCT03122652
- Acronym / sponsor ID
- TERIS / 14-PP-11
- Conditions
- Multiple Sclerosis
- Keywords
- Radiologically Isolated Syndrome
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Collaborators
- Genzyme, a Sanofi Company
- Study start
- 25 Sep 2017 (actual)
- Primary completion
- 5 Feb 2019 (actual)
- Study completion
- 4 Oct 2022 (actual)
- First posted
- 21 Apr 2017 (actual)
- 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.
Multiple sclerosis (MS) is a common cause of severe neurological disability in young adults, resulting from an autoimmune interruption of both myelin and axons within the central nervous system (CNS). The diagnosis is made by fulfilling both spatial criteria, by meeting the requisite number of lesions within the brain or spinal cord, along with criteria for time, by demonstrating a history of at least a second clinical attack or the development of a new MS lesion on MRI after the seminal neurological event. In the case of MS, healthy individuals who do not exhibit signs of neurological dysfunction commonly have brain MRI studies performed for a reason other than an evaluation for MS that reveal unexpected anomalies highly suggestive of demyelinating plaques given their size, location, and morphology. These healthy subjects lack symptomatology suggestive of MS and fulfill formal criteria for radiologically isolated syndrome (RIS), a recently described MS subtype that expands upon the phenotype of at-risk individuals for future demyelinating events. The discovery of such anomalies creates intersecting neuro-ethical, legal, social, and practical medical management quandaries and is, therefore, of both immediate and long-term clinical significance. Despite advancements in the characterization of RIS subjects, and in our understanding of risk factors for initial symptom development, the effect of treatment on such cases remain unclear.
The purpose of this investigation is to systematically study the efficacy of Teriflunomide in those individuals who possess incidental white matter anomalies within the brain and following a MRI study that is performed for a reason other than for the evaluation of MS.
RIS subjects are frequently exposed to disease modifying therapies despite the lack of scientific literature supporting the use of such treatments. Earlier treatment intervention may extend the time to the first acute or progressive clinical event resulting from CNS demyelination and reduce radiological progression. In addition, early treatment may result in more profound effects on reducing disability progression long-term.
The primary outcome measure for this trial is the time to the first acute or progressive neurological event resulting from CNS demyelination.
This study will include RIS subjects from the Europe who fulfill 2009 RIS Criteria.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Terifunomide | Experimental | Drug: Teriflunomide 14 MG Oral Tablet [Aubagio] |
| Placebo | Placebo comparator | Drug: Placebo Oral Tablet |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Males and females of all ages(>18 years and <65 years) meeting 2009 RIS criteria:
- Identified RIS cases with the initial MRI demonstrating anomalies suggestive of demyelinating disease dated ≥ 2009
- Incidental anomalies identified on MRI of the brain or spinal cord with the primary reason for the acquired MRI resulting from an evaluation of a process other than MS
- Affiliation to the social security system
- Subjects of reproductive potential are eligible only if the following applies:
Key exclusion criteria (18 listed)
- Hypersensitivity to the active substance or to any of the excipients listed in section 6.1 of summary of product characteristics (SmPC).
- Patients with severe hepatic impairment (Child-Pugh class C).
- Patients with severe immunodeficiency states, e.g. AIDS.
- Patients with significantly impaired bone marrow function or significant anaemia, leucopenia, neutropenia or thrombocytopenia.
- Patients with severe active infection until resolution.
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 |
|---|---|---|
| Teriflunomide 14 MG Oral Tablet [Aubagio]1 tablet once a day | Drug | Terifunomide |
| Placebo Oral Tablet1 tablet once a day | Drug | Placebo |
Primary outcome
Time to the first acute or progressive neurological event resulting from CNS demyelination.
Time frame: Week 96
Acute neurological event: The development of an acute neurological episode localized to the optic nerve, brainstem, cerebellum, spinal cord, or long sensory or motor tracts, lasting > 24 hours followed by a period of symptom improvement. Progressive event: The onset of a clinical symptom (e.g. leg weakness) with the temporal profile revealing at least a 12-month progression of neurological deficits.
7 secondary outcomes
New or enlarging T2 lesions
Time frame: Week 48
New or enlarging T2 lesions
Time frame: Week 96
New contrast enhancing lesions
Time frame: Week 48
New contrast enhancing lesions
Time frame: Week 96
New T2-lesion volumes
Time frame: Week 48
New T2-lesion volumes
Time frame: Week 96
Brain atrophy
Time frame: Week 96
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Mar 2023.
- Derived from this study: PubMed 37603328Lebrun-Frenay C, Siva A, Sormani MP, Landes-Chateau C, Mondot L, Bovis F, Vermersch P, Papeix C, Thouvenot E, Labauge P, Durand-Dubief F, Efendi H, Le Page E, Terzi M, Derache N, Bourre B, Hoepner R, Karabudak R, De Seze J, Ciron J, Clavelou P, Wiertlewski S, Turan OF, Yucear N, Cohen M, Azevedo C, Kantarci OH, Okuda DT, Pelletier D; TERIS Study Group. Teriflunomide and Time to Clinical Multiple Sclerosis in Patients With Radiologically Isolated Syndrome: The TERIS Randomized Clinical Trial. JAMA Neurol. 2023 Oct 1;80(10):1080-1088. doi: 10.1001/jamaneurol.2023.2815.
- Individual participant dataSharing planned: No
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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.
Christine LEBRUN-FRENAY, MD principal investigator
Centre Hospitalier Universitaire de Nice
23 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Teriflunomide 14 MG Oral Tablet [Aubagio] in people with Multiple Sclerosis, run by Centre Hospitalier Universitaire de Nice at 23 sites in 3 countries.
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 15 inclusion and 18 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 17 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 23 sites in France, Turkey (Türkiye), Switzerland. 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. Some participants in this study may receive a placebo. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Time to the first acute or progressive neurological event resulting from CNS demyelination. (time frame: Week 96). 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 NCT03122652, which also lists 1 linked publication.
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 17 Mar 2023.