MIROCALS: Modifying Immune Response and OutComes in ALS

Phase 2

Completed

• Conditions: Amyotrophic Lateral Sclerosis
• Interventions: Drug: Riluzole; Drug: 5% glucose water solution; Drug: IL-2

• Registration Number: NCT03039673
• Lead Sponsor: Centre Hospitalier Universitaire de Nīmes

Brief 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

Study Timeline

• Study First Submitted: 2017-01-31
• Study First Submitted QC: 2017-01-31
• Study First Posted: 2017-02-01
• Study Start: 2017-06-19
• Primary Completion: 2021-07-22
• Study Completion: 2021-07-22
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-01
• Last Update Posted: 2022-04-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 304

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Riluzole	Patients randomized to this arm will receive subcutaneious placebo injections (5% glucose water solution) in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: 5% glucose water solution
low dose interleukin-2	Riluzole	Patients randomized to this arm will receive subcutaneous injections of low-dose interleukin-2 in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: IL-2
Placebo	5% glucose water solution	Patients randomized to this arm will receive subcutaneious placebo injections (5% glucose water solution) in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: 5% glucose water solution
low dose interleukin-2	IL-2	Patients randomized to this arm will receive subcutaneous injections of low-dose interleukin-2 in addition to oral Riluzole treatment. Intervention: Riluzole Intervention: IL-2

Primary Outcome Measures

Name	Time	Method
Time to death from date of randomization to date of death	Month 21	Time to death from date of randomization to date of death as documented in death certificates, or date of last documented news for patients lost to follow-up, or 640 days for patients who survive more than 640 days (censoring at 640 days). Death certificates are collected by the centre's principal investigator from the City Hall of the patients' home or birth place.

Trial Locations

Locations (17)

CHRU de Lille - Hôpital Roger Salengro; 🇫🇷 Lille, France

CHU de Limoges - Hôpital Dupuytren; 🇫🇷 Limoges, France

HCL - Hôpital Neurologique P. Wertheimer; 🇫🇷 Lyon, France

APHM - Hôpital de la Timone; 🇫🇷 Marseille, France

CHRU de Montpellier - Hôpital Gui de Chauliac; 🇫🇷 Montpellier Cedex 5, France

CHU de Nice - Hôpital Pasteur; 🇫🇷 Nice, France

CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll; 🇫🇷 Saint Brieuc, France

CHU de Strasbourg - Hôpital de Hautepierre; 🇫🇷 Strasbourg, France

CHRU de Tours - Hôpital Bretonneau; 🇫🇷 Tours, France

Trafford Centre for Biomedical Research; 🇬🇧 Brighton, United Kingdom

King's MND Care and Research Centre; 🇬🇧 London, United Kingdom

North-East London and Essex MND Regional Care Centre; 🇬🇧 London, United Kingdom

Centre for Neuromuscular Diseases - National Hospital of Neurology; 🇬🇧 London, United Kingdom

Salford Royal NHS Foundation Trust, Neurology Dept; 🇬🇧 Manchester, United Kingdom

APHP - Groupe Hospitalier Pitié-Salpetrière; 🇫🇷 Paris Cedex 13, France

Institute of Neurological Sciences, Queen Elizabeth University Hospital; 🇬🇧 Glasgow, United Kingdom

Sheffield Care and Research Centre; 🇬🇧 Sheffield, United Kingdom