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

Relapsing Remitting Multiple Sclerosis Clinical Trial

— MS-IL2  

Official title:

Biological Activity and Safety of Low Dose IL2 in Relapsing Remitting Multiple Sclerosis. Multicentric Randomized Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02424396
• Other study ID #: P130102
• Secondary ID: 2014-000088-82
• Status: Completed
• Phase: Phase 2
• Start date: June 13, 2016
• Est. completion date: June 15, 2020

Study information

• Verified date: November 2020
• Source: Assistance Publique - Hôpitaux de Paris
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: June 15, 2020
• Est. primary completion date: October 11, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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 ß-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

Related Conditions & MeSH terms

• Multiple Sclerosis
• Multiple Sclerosis, Relapsing-Remitting
• Relapsing Remitting Multiple Sclerosis
• Sclerosis

Intervention

Drug:
• IL2
Induction period: repeated administration of low-dose IL-2 Maintenance period: treatment with IL-2
• Placebo

Locations

Country	Name	City	State
France	Centre d'investigation Clinique - Pitié salpêtrière	Paris
France	Centre d'investigation clinique Biothérapie Immunologie (CIC-BTi) - Groupe Hospitalier Pitié-Salpêtrière - AP-HP	Paris
France	Département des maladies du système nerveux et Centre d'investigation clinique - Groupe Hospitalier Pitié-Salpêtrière - AP-HP	Paris

Sponsors (2)

Lead Sponsor	Collaborator
Assistance Publique - Hôpitaux de Paris	Fondation ARSEP/AFM

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Treg response to low dose IL2 induction course period, expressed as % of total CD4 cells		at day5
Secondary	Change in Treg percentage on D15 after induction (D1-D5) compared to baseline		at day15
Secondary	Change in Treg percentage from D15 to M6 compared to baseline		Day 15 to Day 169
Secondary	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
Secondary	Frequency of patients free of Gd+ lesions at M6		Day 169
Secondary	The cumulative number of new T2 lesions		Day 169
Secondary	Annual relapse rate (number of relapses observed over a 6 month period)		Day 169
Secondary	% of patients with flare		Day 169
Secondary	% of disease free patient i.e % of patient with no clinical symptoms and no activity on MRI		Day 169