The effect of teriflunomide on brain microglial cell activation in multiple sclerosis.

• Register: EUCTR
• Last refreshed on: 2 October 2017
• Main ID: EUCTR2016-003622-16-FI
• Date of registration: 27/02/2017
• Prospective Registration: Yes
• Primary sponsor: Turku University Hospital
• Public title: The effect of teriflunomide on brain microglial cell activation in multiple sclerosis.
• Scientific title: Targeting SPMS: Effect of teriflunomide treatment on microglial activation in an MS patient cohort at risk of progression. A [11C]PK11195 Brain PET study.
• Date of first enrolment: 19/09/2017
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-003622-16
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: Comparison to MS patients not on therapy and to historical MS patients and healthy controls If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: yes Other specify the comparator: Comparison to MS patients not on therapy. Number of treatment arms in the trial: 1
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Finland

Contacts

• Name: Turku University Hospital
• Affiliation: Turku University Hospital

• Name: Turku University Hospital
• Affiliation: Turku University Hospital

Key inclusion & exclusion criteria

Inclusion criteria:
-Signing the consent form
-Having used teriflunomide treatment for at least 6 months
-40-55 years of age at the time of signing the research consent form
-MS diagnosis in accordance with either the Poser or McDonald criteria
-EDSS 2-6.5
-Clear lesion load in brain MRI (>9 T2 lesions)
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 30
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
-Patients suffering from another brain disease in addition to MS
-Significant pathology in the MRI scan other than MS-related pathology
-Steroid treatment within 4 weeks prior to the scan
-Patients suffering from claustrophobia or panic disorder, or patients who have exhibited hypersensitivity of PET markers (practical obstacle to the scan)
-Exposure to experimental radioactivity in the last 12 months such that the dosimetry threshold would be exceeded due to participation in the study
-Severe hepatic impairment
-Pregnant women, or women of childbearing potential who are not using reliable contraception during treatment with teriflunomide and thereafter as long as its plasma levels are above 0.02 mg/l.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Multiple sclerosis

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Trade Name: AUBAGIO
Product Name: Teriflunomide
Product Code: L04AA31
Pharmaceutical Form: Film-coated tablet

Primary Outcome(s)

Secondary Objective: •To evaluate the total lesion load of the white matter MS plaques at different time points using MRI
•To measure total brain, white matter (WM) and gray matter (GM) volumes using MRI at different time points
•To determine MD (mean diffusity) and FA (fractional anisotropy) using DTI (diffusion tensor imaging) at different time points
•To correlate the baseline microglial activation status to the clinical outcome parameters at the end of the study
•To correlate the baseline microglial activation status to the MRI parameters
•To compare microglial activation in the study group to microglial activation in a group of age-matched healthy controls
•To compare microglial activation in the study group (in the beginning of the study) to microglial activation in an independent group of age-matched untreated MS-patients

Primary end point(s): Change in microglia-activity in RRMS patients on teriflunomide treatment as measured by PET imaging and [11C]PK11195 radioligand.

Main Objective: To perform brain PET imaging with the [11C]PK11195 radioligand to 20 RRMS patients (age 40-55) who are using teriflunomide treatment and to 10 RRMS patients not on therapy. Purpose is to compare the binding of the radioligand between the two different time points and compare the outcomes in the cohorts to see whether teriflunomide treatment alters microglial activation in RRMS.

Timepoint(s) of evaluation of this end point: Baseline and 1 year.

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: MRI at baseline and yearly thereafter.
Clinical outcome parameters and quality of life measurements: baseline and yearly thereafter.
Cognitive variables: baseline and after 3 years.

Secondary end point(s): Comparison of the following MRI parameters
-Evaluation of white matter lesion load in MRI scans (impact of treatment on disease inflammatory activity)
-Evaluation of the total volume of the brain, the volume of white matter and of grey matter in MRI scans (impact of treatment on brain atrophy)
-DTI (diffusion tensor imaging) will be used to measure the MD (mean diffusivity) and FA (fractional anisotropy) MRI scans (impact of treatment on brain atrophy)
All the above mentioned MRI variables will also be correlated to microglial activation and clinical parameters.

Clinical outcome parameters (EDSS, MSFC, MSIS29) and quality of life measurements (SF36, EQ5-D) will be measured and will be correlated with PET and MRI findings to evaluate whether high microglial activation is predictive of higher likelihood of progression and other measures of disability.

Cognitive variables measured using the BICAMS test battery will be correlated with PET and MRI findings.

Secondary ID(s)

T214/2016

Source(s) of Monetary Support

Sanofi-aventis groupe