NCT03039673

MIROCALS: Modifying Immune Response and OutComes in ALS

Efficacy and Safety of Low-dose IL-2 (Ld-IL-2) as a Treg Enhancer for Controlling Neuro-inflammation in Newly Diagnosed Amyotrophic Lateral Sclerosis (ALS) Patients: A Randomized, Double-blind, Placebo- Controlled, Phase-II Proof of Concept/ Proof of Mechanism Clinical Trial

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 304 (actual)
• Sponsor: Centre Hospitalier Universitaire de Nīmes · Academic / Other
• Sex: All
• Age: 18 Years – 75 Years
• Healthy volunteers: Not accepted

Summary

MIROCALS is a phase II study of ld-IL-2 as a therapeutic agent for ALS. A randomized (1:1), placebo-controlled, double-blind, parallel group trial will be carried out to assess ld-IL-2 safety and clinical efficacy on survival and functional decline in newly diagnosed ALS patients treated for 18 months. Randomization will be stratified according to (i) country (n = 2 levels: UK, France) and (ii) site of onset (n= 2 levels: bulbar vs limb onset). The primary objective to evaluate the clinical efficacy and safety of the experimental drug (ld IL-2) over an 18 months period in order to establish the proof of concept (PoC) that modifying immune responses through the enhancement of regulatory T cells modifies the rate of ALS disease progression.

Detailed description

The secondary objectives of MIROCALS are: To validate a new phase-II study design to improve the efficiency of drug development in ALS with early determination of drug response using established biomarkers (BMs). The aims of this new trial design are: (i) To shorten future trials duration in ALS using an early drug responding surrogate marker of disease activity; (ii) To establish the proof of mechanism (PoM) of the tested drugs; (iii) To identify drug responder status. Additional exploratory objectives are: (i) Deep immune \& inflammatory phenotyping (ii) Brain biomarkers (iii) Genomics and Transcriptomics

Conditions

• Amyotrophic Lateral Sclerosis

Interventions

Type	Name	Description
DRUG	Riluzole	All patients will be treated with Riluzole for a period of three months prior to final inclusion and randomization. Riluzole treatment will continue throughout the 18 months of follow-up planned for in this protocol. Riluzole treatment is part of routine care for patients with ALS.
DRUG	IL-2	The dose of IL-2 to be used in this study will be 2.0 million IU/day. Each treatment course will last 5 days (i.e. 1 sub-cutaneous injection per day for 5 consecutive days). The 5-day course will be repeated every 4-weeks over an 18-month treatment period. In case of intolerance, a flexible dose-reduction schedule is available.
DRUG	5% glucose water solution	The placebo consists of 5% glucose water solution, which is the matrix with which low-dose IL-2 injections are prepared in the experimental arm. Placebo injections are prepared in exactly the same manner as IL-2 injections, just without the IL-2. Each treatment course will last 5 days (i.e. 1 sub-cutaneous injection per day for 5 consecutive days). The 5-day course will be repeated every 4-weeks over an 18-month treatment period.

Timeline

• Start date: 2017-06-19
• Primary completion: 2021-07-22
• Completion: 2021-07-22
• First posted: 2017-02-01
• Last updated: 2025-12-04

Locations

17 sites across 2 countries: France, United Kingdom