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• Register: EUCTR
• Last refreshed on: 14 March 2022
• Main ID: EUCTR2016-001515-20-IT
• Date of registration: 07/02/2018
• Prospective Registration: No
• Primary sponsor: UNIVERSITÀ CATTOLICA DEL SACRO CUORE- POLICLINICO A. GEMELLI
• Public title: nd
• Scientific title: EFFECT OF TERIFLUNOMIDE ON T CELL SUBPOPULATIONS IN PERIPHERAL BLOOD FROM RRMS PATIENTS - nd
• Date of first enrolment: 20/10/2016
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2016-001515-20
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: yes; Single blind: no; Double blind: no; Parallel group: Cross over: Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): no Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): yes

Countries of recruitment

Italy

Contacts

• Name: Unità operativa Sclerosi Multipla-
• Affiliation: Fondazione policlinico gemelli

• Name: Unità operativa Sclerosi Multipla-
• Affiliation: Fondazione policlinico gemelli

Key inclusion & exclusion criteria

Inclusion criteria:
Patients of male or female aged> 18 years, with relapsing remitting multiple sclerosis diagnosed according to the McDonald criteria 2010. Only patients candidates to treatment with teriflunomide will be enrolled
Aged between 18-55 years
EDSS between 0-5,5
Patients relapse free for = 30 days prior to study entry
No treatment with immunomodulatory drugs in the last 3 months
Ability to provide written informed consent and be compliant with the timing of the evaluations required by the Protocol
Women of childbearing potential and not complianti highly effective contraceptive measures defined in accordance with the recommendations of the Clinical Trial Facilitation Group (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf)
Male patients with partners of childbearing age who do not belong to highly effective contraceptive measures defined in accordance with the recommendations of Clinical Trial Facilitation Group
Women who are pregnant or breast-feeding (in all women of childbearing age before you start treatment with Teriflunomide will be made the dosage of beta-HCG in serum, and also will be made a urinary pregnancy test every month during treatment as required by the recommendations of the Clinical Trial Facilitation Group)
Highly effective contraceptive measures under specific CTFG the recommendations are as follows:
-patients who use combined hormonal contraceptives (containing estrogen and progesterone) associated with inhibition of ovulation or oral, intravaginal that transdermal
- Patients who use hormonal contraceptives based only progesterone that inhibit ovulation, whether oral, injectable or implantable
- Patients with placement of IUD (intrauterine device)
-patients with positioning of hormone releasing intrauterine systems
- Patients with bilateral tubal occlusion
- Patients with vasectomized partner
- Patients who practice sexual abstinence

Are the trial subjects under 18? no
Number of subjects for this age range: 1
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:
<18 years of age; > 55 years of age.
Patients diagnosed with progressive multiple sclerosis
Onset of disease relapse or treatment with corticosteroids within 30 days prior to study entry
Hypersensitivity to the active substance or to any of the excipients
Patients with severe hepatic impairment (Child-Pugh Class C).
Patients with pre-existing acute or chronic liver disease, or patients with levels of ALT (alanine aminotransferase) greater than 2 times the upper normal limit ULN).
Women of childbearing potential and not compliant to highly effective contraceptive measures defined in accordance with the recommendations of the Clinical Trial Facilitation Group(http://www.hma.eu/fileadmin/dateien/Human_Medicines/01About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf). A ll women of childbearing age before starting treatment with teriflunomide it will be made the dosage of beta-HCG in serum; Also a urine pregnancy test will be performed monthly during treatment as provided by the recommendations of the Clinical Trial Facilitation Group)
Women lactating
Male patients with partners of childbearing age and not complianti highly effective contraceptive measures defined in accordance with the recommendations of the Clinical Trial Facilitation Group
Patients with severe immunodeficiency, such as AIDS (the determination of IgG and IgM serology for HIV type 1 and 2 will be conducted prior to initiating treatment with teriflunomide)
Any patients with severe active infection until resolution.
Patients with latent or active tuberculosis (before starting treatment with teriflunomide will be assayed the Quantiferon test)
Patients with severe renal failure requiring dialysis, there are not adequate clinical experience in this patient group.
Patients with significantly impaired bone marrow function or with anemia, leucopenia, neutropenia or thrombocytopenia.
Patients with severe hypoproteinaemia, eg nephrotic syndrome.
Previous course of treatment with teriflunomide.
Previous treatment with leflunomide (within 6 months prior to baseline).
Concomitant treatment with other immunosuppressive drugs
Medical or psychiatric conditions that compromise the patient's ability to give informed consent, to comply with the evaluation required under the Protocol or to complete the study.
diagnosis of dementia
history of malignancy, including solid tumors and hematologic malignancies
History or laboratory evidence of coagulation disorders
Patients with history or known presence of HBV infection, HCV (before starting treatment with teriflunomide should be performed the following serological tests: HBsAg, HBcAb confirmed by a positive research of HBV-DNA by PCR, anti HCV antibodies).
Patients with history or known presence of syphilis (in the period of screening will be carried out serological tests to determine anti-VDRL antibodies)
Comorbid for other neurological disorders that may mimic multiple sclerosis as neuromyelitis optica, Lyme disease, vitamin B12 deficiency is not treated, neurosarcoidosis and cerebrovascular disorders
abuse of alcohol or drugs.
Any contraindication to perform the Nuclear Magnetic Resonance such as: patients with cardiac pacemakers, insulin infusion pump, medication infusion device, cochlear implants, otological implants, transdermal patch of medications (nitro, hormones), which can cause problems if removed, even temporarily, any metal implants or objects piercing (s), bearers of screws, nails, bone plates, wire

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

Health Condition(s) or Problem(s) studied

RELAPSING-REMITTING MULTIPLE SCLEROSIS
MedDRA version: 20.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders

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

Intervention(s)

Trade Name: AUBAGIO - 14 MG - COMPRESSA RIVESTITA CON FILM - USO ORALE - BLISTER (ALU/ALU) - 28 COMPRESSE
Product Name: teriflunomide
Product Code: nd
Pharmaceutical Form: Film-coated tablet

Primary Outcome(s)

Primary end point(s): To evaluate the correlation between hange of the subpopulations of effector pro-inflammatory and anti-inflammatory T cells (% Th1 +% TC1 +% Th17 +% Tc17-% Th2) characterized by flow cytometry analysis, at baseline and during the early stages of treatment with teriflunomide to clinical and radiological response in one year of therapy.

Timepoint(s) of evaluation of this end point: 12 months

Secondary Objective: To evaluate the effect of teriflunomide on the immune response, to better characterize which phenotype of immune response is principally involved in the drug mechanism of action. In particular, this study will evaluate the effects of teriflunomide on the ratio of pro-inflammatory cells (Th1 / Th17) and anti-inflammatory cells (Th2 / Treg) in peripheral blood of patients with RRMS.

Main Objective: The immunological profile of patients with multiple sclerosis is defined by the mutual balance of subpopulations of effector T cells, expressed as a sum of subpopulations of effector pro-inflammatory T cells and anti-inflammatory T cells (% Th1 +% TC1 +% Th17 +% Tc17-% Th2) .
Immunomodulatory drugs are able to modulate the immune response by altering the ratio of these T cell subpopulation.
The primary objective of the study is to evaluate the immunological profile at baseline and its variation during the early stages of treatment with teriflunomide that might be a predictor of clinical and radiological response to therapy. Specifically, a regulatory pattern of lymphocyte subtypes represented by a higher ratio of regulatory T cells than the effector T cells, may be an optimal response markers during therapy with teriflunomide.

Secondary Outcome(s)

Secondary end point(s): To Assess the change from baseline in the subgroup of effector pro-inflammatory and anti-inflammatory T cells (% Th1 +% TC1 +% Th17 +% Tc17-% Th2) analyzed by flow cytometry, during treatment with teriflunomide to characterize which phenotype of immune response is primarily involved in the mechanism of action of the drug.

Timepoint(s) of evaluation of this end point: 12 months

Secondary ID(s)

12971/16

Source(s) of Monetary Support

genzyme

Ethics review

Status: Approved
Approval date: 20/10/2016
Contact: