Biological Activity and Safety of Low Dose IL2 in Relapsing Remitting Multiple Sclerosis

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