Biological Activity and Safety of Low Dose IL2 in Relapsing Remitting Multiple Sclerosis. Multicentric Randomized Study
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 3
- 主要终点
- Treg response to low dose IL2 induction course period, expressed as % of total CD4 cells
研究概览
简要总结
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
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
1 : IL2
Interleukin-2 (ILT-101)
干预措施: IL2 (Drug)
2 : Placebo
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Treg response to low dose IL2 induction course period, expressed as % of total CD4 cells
时间窗: at day5
次要结局
- Change in Treg percentage on D15 after induction (D1-D5) compared to baseline(at day15)
- 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)
- The cumulative number of new T2 lesions(Day 169)
- Annual relapse rate (number of relapses observed over a 6 month period)(Day 169)
- Change in Treg percentage from D15 to M6 compared to baseline(Day 15 to Day 169)
- Frequency of patients free of Gd+ lesions at M6(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)