Multiple SclerosisPhase 3TERI-DYNAMICNCT01863888
Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Multiple Sclerosis
A Phase 3 study testing teriflunomide HMR1726, cholestyramine and charcoal in people with Multiple Sclerosis, run by Sanofi at 10 sites in 3 countries.
Trial summary
Primary Objective: To measure the effect of Teriflunomide on lymphocytes subsets in patients with relapsing forms of multiple sclerosis as compared with baseline values and those of a reference population of untreated healthy subjects. Read more about this study
- Who is it for?
- Ages 18 to 55 yearsHealthy volunteers can take part
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- teriflunomide HMR1726, cholestyramine and charcoal
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 10 sitesin 3 countries
- Study dates
- Oct 2013to Jan 2015
- 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 to 55 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Patients (male and female) with relapsing forms of multiple sclerosis meeting McDonald criteria for MS at the screening visit and having either one of the following treatment status:
- Naïve to disease modifying (DM) treatment or no DM treatment for more than 2 years
- Or currently (not more than 3 months interruption) on MS therapy with IFN β-1 or Glatiramer acetate and a period of at least 2 weeks without IFN β-1 or Glatiramer acetate before switching to teriflunomide.
- Male and female patients, between 18 and 56 years of age, exclusive.
- Healthy volunteers:
- Male and female subjects, between 18 and 56 years of age, exclusive. Body weight between 50.0 and 95.0 kg, inclusive, if male; and between 40.0 and 85.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.
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- Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination).
- Normal vital signs after 10 minutes resting in supine position:
- 95 mmHg < systolic blood pressure (SBP) <140 mmHg
- 45 mmHg < diastolic blood pressure (DBP) <90 mmHg
- 40 bpm < heart rate (HR) <100 bpm Normal standard 12-lead electrocardiogram (ECG) after 10 minutes resting in supine position; 120 ms < PR <220 ms, QRS <120 ms, QTc ≤ 430 ms if male, ≤ 450 ms if female.
- Laboratory parameters within the normal range (or defined screening threshold for the Investigator site), unless the Investigator considers an abnormality to be clinically irrelevant for healthy subjects; however liver function parameter(s) should not exceed the upper laboratory norm.
Who cannot join
- Did not consent to HIV testing (the specifics of informed consent process for the HIV testing should be done in accordance with local guidelines).
- A relapse within 30 days prior to screening. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the patient at risk by participating in the study.
- Patients with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymphoproliferative disease, or any patient who has received lymphoid irradiation.
- Human immunodeficiency virus (HIV) positive patients. Known history of active tuberculosis not adequately treated or positive QuantiFERON TB Gold test.
- Hypoproteinemia (eg, in case of severe liver disease or nephrotic syndrome) with serum albumin <3.0 g/dL.
- Moderate to severe impairment of renal function, as shown by serum creatinine >133 μmol/L (or >1.5 mg/dL).
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- Patients with significantly impaired bone marrow function or significant anemia, leukopenia, or thrombocytopenia.
- Acute or chronic infection. Liver function impairment or persisting elevations >1.5ULN (confirmed by retest) of serum glutamic pyruvic transaminase/ alanine aminotransferase (SGPT/ALT), serum glutamic oxaloacetic transaminase/aspartate aminotransferase (SGOT/AST), or direct bilirubin greater than 1.5-fold the upper limit of normal.
- Use of adrenocorticotrophic hormone (ACTH) or systemic corticosteroids for 2 weeks prior to screening.
- Prior or concomitant use of cytokine therapy or intravenous immunoglobulins in the 3 months prior to screening.
- Prior use of alemtuzumab or cladribine. Prior use (within 1 year) of fingolimod (Gylenia®). Prior use (within 2 years) of mitoxantrone, natalizumab (Tysabri®), or immunosuppressant agents (i.e. azathioprine, cyclophosphamide, cyclosporin, methotrexate or mycophenolate).
- Prior treatment with teriflunomide, and prior or concomitant use of leflunomide (ARAVA®) or hypersensitivity to any of the other ingredients or excipients of the investigational product.
- Prior use of any investigational drug in the 6 months preceding screening. Pregnant or breast-feeding women. Women of childbearing potential not utilizing effective contraceptive method and /or women of childbearing potential who are unwilling to or unable to be tested for pregnancy.
- 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.
- The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Trial locations and contacts
10 sites in 3 countries.
10 sites in 3 countries
Germany6 sites
Investigational Site Number 276-003
Bad Mergentheim, 97980
Investigational Site Number 276-004
Hanover, 30625
Investigational Site Number 276-005
Marburg, 35043
Investigational Site Number 276-007
Mönchengladbach, 41061
Investigational Site Number 276-001
Münster, 48149
Investigational Site Number 276-002
Ulm, 89073
Belgium3 sites
Investigational Site Number 056001
Brussels, 1070
Investigational Site Number 056002
Overpelt, 3900
Investigational Site Number 056003
Sijsele-Damme, 8340
Netherlands1 site
Investigational Site Number 528001
Sittard-Geleen, 6162BG
About this study
Official title: Exploratory Open Label Study to Investigate the Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Relapsing Forms of Multiple Sclerosis
Primary Objective:
To measure the effect of Teriflunomide on lymphocytes subsets in patients with relapsing forms of multiple sclerosis as compared with baseline values and those of a reference population of untreated healthy subjects.
Read more
Secondary Objectives:
To assess if Teriflunomide treatment results in biased T cell clonal diversity. To assess the effect of Teriflunomide on the function of peripheral blood mononuclear cells (proliferation and cytokine production in situ).
To assess the circulating cytokines profile in the serum of Relapsing Multiple Sclerosis (RMS) patients during a 24-week treatment versus baseline and healthy controls.
To assess the reversibility of all parameter changes in patients who discontinue treatment after accelerated elimination procedure with cholestyramine or activated charcoal.
Read the detailed description
The duration of the study for patients is 32 weeks which includes 4 weeks for screening, 24 weeks for treatment and 4 weeks for follow-up. An extension of the study is proposed until Teriflunomide is commercially available in the country where patient lives.
The duration of the study for healthy volunteers is 25 weeks which includes only one week for screening.
- Conditions
- Multiple Sclerosis
- Being tested
- teriflunomide HMR1726, cholestyramine, charcoal
- 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 HMR1726Drug
Pharmaceutical form:tablet Route of administration: oral
cholestyramineDrug
Pharmaceutical form:powder Route of administration: oral
charcoalDrug
Pharmaceutical form:granule Route of administration: oral
| Study group | Role | What they receive |
|---|---|---|
| teriflunomide (HMR1726) | Experimental | Participants administered 14mg Teriflunomide once daily, oral. For participants who permanently discontinue Teriflunomide, an accelerated elimination procedure with either cholestyramine or charcoal will be administered. Receives: Drug: teriflunomide HMR1726; Drug: cholestyramine; Drug: charcoal |
| Reference population | No intervention | Untreated healthy subjects |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in Lymphocyte subset parameters as measured by flow cytometry
Measured: At 12 weeks and 24 weeks
Secondary outcomes (3)
Change from baseline in biased T cell clonal repertoire based T cell receptor (TCR) spectratyping
Measured: At 12 weeks and 24 weeks
Change from baseline in serum cytokine as measured by multicytokine array tool
Measured: At 12 weeks and 24 weeks
Change from baseline in Mitogen/TCR-specific T cell proliferation as measured by flow cytometry
Measured: At 12 weeks and 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2013 (estimated)
- Study startOct 2013
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by SanofiThe 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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Sciences & Operations, Study director, Sanofi
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01863888
- Sponsor's protocol ID
- LPS13539
- Other IDs
- U1111-1139-8802
- Acronym
- TERI-DYNAMIC
- Status last verified
- Mar 2015
- First submitted
- 23 May 2013
- Last updated
- 13 Mar 2015
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Exploratory Open Label Study to Investigate the Effect of Teriflunomide on Immune Cell Subsets in the Blood of Patients With Relapsing Forms of Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT01863888
- Acronym / sponsor ID
- TERI-DYNAMIC / LPS13539
- Conditions
- Multiple Sclerosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Oct 2013
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 29 May 2013 (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.
Primary Objective:
To measure the effect of Teriflunomide on lymphocytes subsets in patients with relapsing forms of multiple sclerosis as compared with baseline values and those of a reference population of untreated healthy subjects.
Secondary Objectives:
To assess if Teriflunomide treatment results in biased T cell clonal diversity. To assess the effect of Teriflunomide on the function of peripheral blood mononuclear cells (proliferation and cytokine production in situ).
To assess the circulating cytokines profile in the serum of Relapsing Multiple Sclerosis (RMS) patients during a 24-week treatment versus baseline and healthy controls.
To assess the reversibility of all parameter changes in patients who discontinue treatment after accelerated elimination procedure with cholestyramine or activated charcoal.
Detailed description
The duration of the study for patients is 32 weeks which includes 4 weeks for screening, 24 weeks for treatment and 4 weeks for follow-up. An extension of the study is proposed until Teriflunomide is commercially available in the country where patient lives.
The duration of the study for healthy volunteers is 25 weeks which includes only one week for screening.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| teriflunomide (HMR1726) | Experimental | Drug: teriflunomide HMR1726, Drug: cholestyramine, Drug: charcoalParticipants administered 14mg Teriflunomide once daily, oral. For participants who permanently discontinue Teriflunomide, an accelerated elimination procedure with either cholestyramine or charcoal will be administered. |
| Reference population | No intervention | –Untreated healthy subjects |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (12 listed)
- Patients (male and female) with relapsing forms of multiple sclerosis meeting McDonald criteria for MS at the screening visit and having either one of the following treatment status:
- Naïve to disease modifying (DM) treatment or no DM treatment for more than 2 years
- Or currently (not more than 3 months interruption) on MS therapy with IFN β-1 or Glatiramer acetate and a period of at least 2 weeks without IFN β-1 or Glatiramer acetate before switching to teriflunomide.
- Male and female patients, between 18 and 56 years of age, exclusive.
- Male and female subjects, between 18 and 56 years of age, exclusive. Body weight between 50.0 and 95.0 kg, inclusive, if male; and between 40.0 and 85.0 kg, inclusive, if female, body mass index between 18.0 and 30.0 kg/m2, inclusive.
Key exclusion criteria (16 listed)
- Did not consent to HIV testing (the specifics of informed consent process for the HIV testing should be done in accordance with local guidelines).
- A relapse within 30 days prior to screening. Clinically relevant cardiovascular, neurological, endocrine, or other major systemic disease making implementation of the protocol or interpretation of the study results difficult or that would put the patient at risk by participating in the study.
- Patients with a congenital or acquired severe immunodeficiency, a history of cancer (except for basal or squamous cell skin lesions which have been surgically excised, with no evidence of metastasis), lymphoproliferative disease, or any patient who has received lymphoid irradiation.
- Human immunodeficiency virus (HIV) positive patients. Known history of active tuberculosis not adequately treated or positive QuantiFERON TB Gold test.
- Hypoproteinemia (eg, in case of severe liver disease or nephrotic syndrome) with serum albumin <3.0 g/dL.
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 HMR1726Pharmaceutical form:tablet Route of administration: oral | Drug | teriflunomide (HMR1726) |
| cholestyraminePharmaceutical form:powder Route of administration: oral | Drug | teriflunomide (HMR1726) |
| charcoalPharmaceutical form:granule Route of administration: oral | Drug | teriflunomide (HMR1726) |
Primary outcome
Change from baseline in Lymphocyte subset parameters as measured by flow cytometry
Time frame: At 12 weeks and 24 weeks
3 secondary outcomes
Change from baseline in biased T cell clonal repertoire based T cell receptor (TCR) spectratyping
Time frame: At 12 weeks and 24 weeks
Change from baseline in serum cytokine as measured by multicytokine array tool
Time frame: At 12 weeks and 24 weeks
Change from baseline in Mitogen/TCR-specific T cell proliferation as measured by flow cytometry
Time frame: At 12 weeks and 24 weeks
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 13 Mar 2015.
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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.
Clinical Sciences & Operations study director
Sanofi
10 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 HMR1726, cholestyramine and charcoal in people with Multiple Sclerosis, run by Sanofi at 10 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 12 inclusion and 16 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 13 Mar 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in Germany, Belgium, Netherlands. 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 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?
Change from baseline in Lymphocyte subset parameters as measured by flow cytometry (time frame: At 12 weeks and 24 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 Mar 2015.