MIROCALS: Modifying Immune Response and OutComes in ALS

NCT ID: NCT03039673

Last Updated: 2025-12-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

304 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-06-19

Study Completion Date

2021-07-22

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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

See the medical conditions and disease areas that this research is targeting or investigating.

Amyotrophic Lateral Sclerosis

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

low dose interleukin-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

Group Type EXPERIMENTAL

Riluzole

Intervention Type DRUG

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.

IL-2

Intervention Type DRUG

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.

Placebo

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

Group Type PLACEBO_COMPARATOR

Riluzole

Intervention Type DRUG

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.

5% glucose water solution

Intervention Type DRUG

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.

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

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.

Intervention Type 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.

Intervention Type 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.

Intervention Type DRUG

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

low dose interleukin-2 ultra low dose interleukin-2

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* Patient is 18 years old and less than 76 years old
* Possible, Probable, Probable laboratory-supported or Definite ALS as defined by El Escorial Revised ALS diagnostic criteria
* Disease duration \<= 24 months
* Slow Vital capacity \>= 70% of normal
* No prior or present riluzole treatment
* Lumbar punctures accepted by patient and done

Exclusion Criteria

* Other neurodegenerative disease that could explain signs or symptoms
* Contra indication for lumbar puncture (history of allergy to xylocaine, presence of contra-indicated treatment, or coagulation test abnormality, clinically significant coagulopathy or thrombocytopenia)
* Non authorized treatment
* Other disease or disorders that could preclude functional assessment, or life-threatening disorders
* Any documented, active, past or present, auto-immune disorders except asymptomatic Hashimoto thyroiditis
* Using assisted ventilation
* Feeding through gastrostomy or nasogastric tube
* Women of child-bearing potential or sexually active man without contraception
* Pregnant or breast feeding woman
* Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride, glucose, CK, ferritin)
* History of documented symptomatic and treated asthma within the past 5 years
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Nigel Leigh, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Brighton and Sussex Medical School

Gilbert Bensimon, MD, PhD

Role: STUDY_DIRECTOR

Centre Hospitalier Universitaire de Nîmes

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

CHRU de Lille - Hôpital Roger Salengro

Lille, , France

Site Status

CHU de Limoges - Hôpital Dupuytren

Limoges, , France

Site Status

HCL - Hôpital Neurologique P. Wertheimer

Lyon, , France

Site Status

APHM - Hôpital de la Timone

Marseille, , France

Site Status

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, , France

Site Status

CHU de Nice - Hôpital Pasteur

Nice, , France

Site Status

APHP - Groupe Hospitalier Pitié-Salpetrière

Paris, , France

Site Status

CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll

Saint-Brieuc, , France

Site Status

CHU de Strasbourg - Hôpital de Hautepierre

Strasbourg, , France

Site Status

CHRU de Tours - Hôpital Bretonneau

Tours, , France

Site Status

Trafford Centre for Biomedical Research

Brighton, , United Kingdom

Site Status

Institute of Neurological Sciences, Queen Elizabeth University Hospital

Glasgow, , United Kingdom

Site Status

North-East London and Essex MND Regional Care Centre

London, , United Kingdom

Site Status

King's MND Care and Research Centre

London, , United Kingdom

Site Status

Centre for Neuromuscular Diseases - National Hospital of Neurology

London, , United Kingdom

Site Status

Salford Royal NHS Foundation Trust, Neurology Dept

Manchester, , United Kingdom

Site Status

Sheffield Care and Research Centre

Sheffield, , United Kingdom

Site Status

Countries

Review the countries where the study has at least one active or historical site.

France United Kingdom

References

Explore related publications, articles, or registry entries linked to this study.

Bensimon G, Leigh PN, Tree T, Malaspina A, Payan CA, Pham HP, Klaassen P, Shaw PJ, Al Khleifat A, Amador MDM, Attarian S, Bell SM, Beltran S, Bernard E, Camu W, Corcia P, Corvol JC, Couratier P, Danel V, Debs R, Desnuelle C, Dimitriou A, Ealing J, Esselin F, Fleury MC, Gorrie GH, Grapperon AM, Hesters A, Juntas-Morales R, Kolev I, Lautrette G, Le Forestier N, McDermott CJ, Pageot N, Salachas F, Sharma N, Soriani MH, Sreedharan J, Svahn J, Verber N, Verschueren A, Yildiz O, Suehs CM, Saker-Delye S, Muller C, Masseguin C, Hajduchova H, Kirby J, Garlanda C, Locati M, Zetterberg H, Asselain B, Al-Chalabi A; MIROCALS Study Group. Efficacy and safety of low-dose IL-2 as an add-on therapy to riluzole (MIROCALS): a phase 2b, double-blind, randomised, placebo-controlled trial. Lancet. 2025 May 24;405(10492):1837-1850. doi: 10.1016/S0140-6736(25)00262-4. Epub 2025 May 9.

Reference Type RESULT
PMID: 40354799 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

2015-005347-14

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

H2020/PHRC-N/2014/GB-01

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

MRG-001 in Patients With Amyotrophic Lateral Sclerosis
NCT06315608 NOT_YET_RECRUITING PHASE2
A Trial of Tocilizumab in ALS Subjects
NCT02469896 COMPLETED PHASE2
Study in ALS With Abatacept & IL-2
NCT06307301 ACTIVE_NOT_RECRUITING PHASE1
The Effect of RNS60 on ALS Biomarkers
NCT03456882 COMPLETED PHASE2
Intermediate-Sized Expanded Access Study
NCT05597436 NO_LONGER_AVAILABLE
Regulatory T Cells for Amyotrophic Lateral Sclerosis
NCT05695521 ACTIVE_NOT_RECRUITING PHASE1