Relapsing Remitting Multiple Sclerosis
Conditions
Keywords
Interleukin 2, IL2, Relapsing Remitting Multiple Sclerosis, Autoimmune diseases, Regulatory T cells, Tregs
Brief summary
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
Detailed description
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.
Interventions
DRUGIL2
Induction period: repeated administration of low-dose IL-2 Maintenance period: treatment with IL-2
DRUGPlacebo
Sponsors
Fondation ARSEP/AFM
Assistance Publique - Hôpitaux de Paris
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Treg response to low dose IL2 induction course period, expressed as % of total CD4 cells | at day5 |
Secondary
| Measure | Time frame |
|---|---|
| Change in Treg percentage from D15 to M6 compared to baseline | Day 15 to Day 169 |
| The cumulative number of new lesions enhanced by Gd+ (Sum of Gd + lesions on T1 MRI on M2, M4 and M6) | Day 57, Day 113 and Day 169 |
| Frequency of patients free of Gd+ lesions at M6 | Day 169 |
| Change in Treg percentage on D15 after induction (D1-D5) compared to baseline | at day15 |
| Annual relapse rate (number of relapses observed over a 6 month period) | Day 169 |
| % of patients with flare | Day 169 |
| % of disease free patient i.e % of patient with no clinical symptoms and no activity on MRI | Day 169 |
| The cumulative number of new T2 lesions | Day 169 |
Countries
France
Outcome results
None listed