NCT03039673

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.

Trial Health

90
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
304

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Jun 2017

Typical duration for phase_2

Geographic Reach
2 countries

17 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 31, 2017

Completed
1 day until next milestone

First Posted

Study publicly available on registry

February 1, 2017

Completed
5 months until next milestone

Study Start

First participant enrolled

June 19, 2017

Completed
4.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 22, 2021

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 22, 2021

Completed
Last Updated

December 4, 2025

Status Verified

November 1, 2025

Enrollment Period

4.1 years

First QC Date

January 31, 2017

Last Update Submit

November 26, 2025

Conditions

Amyotrophic Lateral Sclerosis

Keywords

interleukin-2low-dose interleukin-2

Outcome Measures

Primary Outcomes (1)

  • Time to death from date of randomization to date of death

    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.

    Month 21

Study Arms (2)

low dose interleukin-2

EXPERIMENTAL

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

Drug: RiluzoleDrug: IL-2

Placebo

PLACEBO COMPARATOR

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

Drug: RiluzoleDrug: 5% glucose water solution

Interventions

RiluzoleDRUG

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.

Placebolow dose interleukin-2
IL-2DRUG

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.

Also known as: low dose interleukin-2, ultra low dose interleukin-2
low dose interleukin-2
5% glucose water solutionDRUG

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.

Placebo

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (17)

CHRU de Lille - Hôpital Roger Salengro

Lille, 59037, France

Location

CHU de Limoges - Hôpital Dupuytren

Limoges, 87042, France

Location

HCL - Hôpital Neurologique P. Wertheimer

Lyon, 69677, France

Location

APHM - Hôpital de la Timone

Marseille, 13385, France

Location

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, 34295, France

Location

CHU de Nice - Hôpital Pasteur

Nice, 06002, France

Location

APHP - Groupe Hospitalier Pitié-Salpetrière

Paris, 75651, France

Location

CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll

Saint-Brieuc, 22027, France

Location

CHU de Strasbourg - Hôpital de Hautepierre

Strasbourg, 67098, France

Location

CHRU de Tours - Hôpital Bretonneau

Tours, 37044, France

Location

Trafford Centre for Biomedical Research

Brighton, BN1 9RY, United Kingdom

Location

Institute of Neurological Sciences, Queen Elizabeth University Hospital

Glasgow, G514TF, United Kingdom

Location

North-East London and Essex MND Regional Care Centre

London, E1 4NS, United Kingdom

Location

King's MND Care and Research Centre

London, SE5 8AF, United Kingdom

Location

Centre for Neuromuscular Diseases - National Hospital of Neurology

London, WC1N 3BG, United Kingdom

Location

Salford Royal NHS Foundation Trust, Neurology Dept

Manchester, M6 8HD, United Kingdom

Location

Sheffield Care and Research Centre

Sheffield, S10 2JF, United Kingdom

Location

Related Publications (1)

  • 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.

    PMID: 40354799RESULT

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

RiluzoleInterleukin-2

Condition Hierarchy (Ancestors)

Spinal Cord DiseasesCentral Nervous System DiseasesNervous System DiseasesMotor Neuron DiseaseNeurodegenerative DiseasesTDP-43 ProteinopathiesNeuromuscular DiseasesProteostasis DeficienciesMetabolic DiseasesNutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

ThiazolesSulfur CompoundsOrganic ChemicalsBenzothiazolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingInterleukinsCytokinesIntercellular Signaling Peptides and ProteinsPeptidesAmino Acids, Peptides, and ProteinsLymphokinesProteinsBiological Factors

Study Officials

  • Nigel Leigh, MD, PhD

    Brighton and Sussex Medical School

    PRINCIPAL INVESTIGATOR

  • Gilbert Bensimon, MD, PhD

    Centre Hospitalier Universitaire de Nîmes

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 31, 2017

First Posted

February 1, 2017

Study Start

June 19, 2017

Primary Completion

July 22, 2021

Study Completion

July 22, 2021

Last Updated

December 4, 2025

Record last verified: 2025-11

Data Sharing

IPD Sharing
Will share

Locations

FR(10)GB(7)