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

NCT ID: NCT02424396

Last Updated: 2020-11-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-13
• Study Completion Date: 2020-06-15

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.

Conditions

Relapsing Remitting Multiple Sclerosis

Keywords

Interleukin 2, IL2; Relapsing Remitting Multiple Sclerosis; Autoimmune diseases; Regulatory T cells, Tregs

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1 : IL2

Interleukin-2 (ILT-101)

Group Type: EXPERIMENTAL

IL2

Intervention Type: DRUG

Induction period: repeated administration of low-dose IL-2 Maintenance period: treatment with IL-2

2 : Placebo

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Interventions

IL2

Induction period: repeated administration of low-dose IL-2 Maintenance period: treatment with IL-2

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Eligibility Criteria

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
• 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondation ARSEP/AFM

UNKNOWN

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

David Klatzmann

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

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, , France

Countries

France

References

Louapre C, Rosenzwajg M, Golse M, Roux A, Pitoiset F, Adda L, Tchitchek N, Papeix C, Maillart E, Ungureanu A, Charbonnier-Beaupel F, Galanaud D, Corvol JC, Vicaut E, Lubetzki C, Klatzmann D. A randomized double-blind placebo-controlled trial of low-dose interleukin-2 in relapsing-remitting multiple sclerosis. J Neurol. 2023 Sep;270(9):4403-4414. doi: 10.1007/s00415-023-11690-6. Epub 2023 May 28.

Reference Type: DERIVED

PMID: 37245191 (View on PubMed)

Other Identifiers

2014-000088-82

Identifier Type: OTHER

Identifier Source: secondary_id

P130102

Identifier Type: -

Identifier Source: org_study_id