Biological Activity and Safety of Low Dose IL2 in Relapsing Remitting Multiple Sclerosis
Biological Activity and Safety of Low Dose IL2 in Relapsing Remitting Multiple Sclerosis
Interleukin-2 (IL-2) was initially discovered and used as a stimulator of effector T
 lymphocytes (Teffs), but is now viewed as a very promising immunoregulatory drug having the
 capacity to stimulate regulatory T cells (Tregs). At low dose, Il-2 tips the Treg/Teff
 balance towards Tregs. Recently, it has been shown that Tregs of MS patients have reduced
 proliferative potential. MS-IL2 will assess the safety and biological efficacy of low-dose
 IL2 as a Treg inducer in a Relapsing-Remitting Multiple Sclerosis (RRMS), with the aim to
 stimulate Treg and define potential clinical benefits
In MS-IL2, 30 RRMS patients will be treated in a randomized, double-blind, placebo controlled
 clinical trial. IL-2 will be administered first as an induction course of IL-2 or placebo
 each day for 5 days, followed by a maintenance course at the same dose or placebo every two
 weeks over 6 months.

 The primary efficacy criteria will be the % change from baseline in Treg at day-5, which is
 indicative of the biological response to IL-2.

 The secondary efficacy criteria will be (i) the maintenance of regulatory T cells during the
 6 months of treatment with IL-2 vs. placebo and (ii) the stabilization or regression of the
 disease as determined by disease activity parameters assessed by MRI (cumulative number of
 new lesions in T1 enhanced by gadolinium after 6 months) in the groups treated with IL-2
 compared to placebo.

 Expected impact: MS-IL2 will define which patient respond to IL2 and which doses prevent
 relapses in RRMS. In addition, the deep phenomics studies will further provide the foundation
 for a clinical phase II to define clinical efficacy.
Inclusion Criteria:

 -  Age 18-65 years old ;

 -  Male and Female;

 -  Presenting relapsing remitting multiple sclerosis as determined by revised McDonald
 criteria (2010) ;

 -  On MRI : 1) Presenting 1-2 lesions enhanced by gadolinium (Gd+) (T1) without clinical
 expression of the disease clinique upon inclusion or 6 months prior to inclusion or 2)
 presenting one new lesion T2

 -  Expanded Disability Status Scale (EDSS) score comprised between 0 and 6;

 -  No flare (with or without any corticosteroid therapy) for the past 2 months

 -  Under β-Interferon treatment for ≥ 6 months ; or any other first-line treatment of the
 Relapsing-Remitting Multiple Sclerosis (RRMS): Dimethyl fumarate or teriflunomide
 treatment for ≥ 6 months or glatiramer acetate for ≥ 9 months

 -  For women of childbearing age, contraception for more than 2 weeks upon confirmation
 of inclusion criteria and negative Beta HCG on inclusion visit (D-30 to D-7);

 -  Patient informed consent should be signed by the patient and investigator before
 performing any clinical examination required for the study.

 -  Affiliation to the French Social Security Regimen

 Exclusion Criteria:

 -  Number of lesions enhanced by gadolinium (Gd+) on MRI in T1 > 2 upon inclusion;

 -  Known intolerance to IL2 (see SPC):

 -  Hypersensibility to active substance or one of the excipients ;

 -  Signs of evolving infection requiring treatment

 -  Other clinically significant chronic disorders (beside RR-MS)

 -  History of organ allograft

 -  Administration of a non-authorized treatment; bolus of corticosteroids in the last 2
 months, or treatment with cyclophosphamide, mitoxantrone, or rituximab in the last 6
 months;

 -  Heart failure (≥ grade III NYHA), renal insufficiency, or hepatic insufficiency
 (transaminase>5N), or lung failure

 -  White blood cell count <3000 /mm3, lymphocytes< 1000 /mm3, platelets <150 000 /mm3

 -  Poor venous access not allowing repeated blood tests

 -  Vaccination with live attenuated virus in the months preceding the inclusion or
 planned during the study

 -  Surgery with general anaesthesia during the last 2 months or surgery planned during
 the study

 -  Participation in other biomedical research in the last one month or planned during the
 study

 -  Concomitant psychiatric disease or any other chronic illness or drug-abuse that could
 interfere with the ability to comply with the protocol or to give informed consent

 -  Cancer or history of cancer cured for less than five years (except in situ carcinoma
 of the cervix or basocellular carcinoma)

 -  Pregnant or lactating women;

 -  Men and women of childbearing potential without effective contraception for the
 duration of treatment

 -  Patients under a measure of legal protection