MIROCALS: Modifying Immune Response and OutComes in ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2

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
    

Intervention name(s): Riluzole; IL-2; 5% glucose water solution
Intervention type(s): Drug; Drug; Drug
Intervention description(s): 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.; 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.; 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.
Other intervention name(s): low dose interleukin-2; ultra low dose interleukin-2
Intervention MeSH terms: Interleukin-2; Riluzole
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: interleukin-2; low-dose interleukin-2