MIROCALS

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 randomised, double-blind, placebo-controlled, phase two proof of concept / proof of mechanism clinical trial

UK Chief Investigator

Professor Nigel Leigh

Research summary

ALS is a devastating, disabling and rare disease which progressively breaks down and damages the nerve cells in the brain and spine. It affects approximately 50,000 people in the EU at any time and approximately 10,000 deaths each year. Some interventions are provided to manage the symptoms of this disease, but care is largely supportive and palliative.

The cost to society and to individuals is significant; much of it is health care costs. There is a pressing need to find disease-modifying therapies that will slow disease progression, increase survival and better quality of life.

Riluzole is still the only agent shown to modify survival in ALS but its affects are modest. This tells us that modifying disease progression is a realistic goal in ALS.

Research has shown neuroinflammation significantly contributes to neuronal damage. It is thought if this neuroinflammation can be modified this targeted therapy would be very effective in ALS patients. Previous therapeutic attempts targeted the suppression of all immuno-inflammatory cells, but the risks of toxicity outweighed the benefits of drug effect.

Targeting specific regulatory T-cells called Tregs has shown to reduce neuroinflammation more safely and effectively and low dose IL-2 (ld-IL2) acts through these Tregs.

This study is a randomised, double-blind, placebo-controlled, parallel group, stratified study (country (UK vs France) and site of disease onset (limb vs bulbar)). Bulbar region is lower part of the skull. It investigates the efficacy and safety of low-dose IL2 therapy for 18 months as an add-on therapy with riluzole, and compares the efficacy and safety to riluzole plus placebo in recently diagnosed ALS patients.

The study will take place in five hospitals in England (and five hospitals in France) and will run for 36 months. They hope to recruit 72 patients in the UK from October 2016 (216 patients in total across France and UK).

Inclusion / exclusion criteria

Key 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.

Key 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 authorised 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 five years.

Note: Other protocol defined inclusion / exclusion criteria may apply.

Current status

Study results published

Locations

Brighton – Principal Investigator: Professor Nigel Leigh

Glasgow – Principal Investigator: Dr George Gorrie

London (King's College Hospital) – Principal Investigator: Professor Ammar Al-Chalabi

London (Royal London Hospital) – Principal Investigator: Dr Andrea Malaspina

London (UCL/National Hospital for Neurology and Neurosurgery) – Principal Investigator: Dr Nikhil Sharma

Salford – Principal Investigator: Dr John Ealing

Sheffield – Principal Investigator: Professor Dame Pamela Shaw

Information about study sites

Recruitment groups

Patients with MND

Recruitment targets

• UK target: approximately 80 patients enrolled, to reach 72 randomised patients.

• Global target: 216 randomised patients.

Key dates

Study start date: 19 June 2017 (global)

Planned recruitment close date: 30 June 2019

Target study completion date: June 2021

Results published: 9th May 2025

Sponsor

Centre Hospitalier Universitaire de Nīmes

Study design

Interventional (clinical trial)

Intervention

• Drug: IL-2

• Drug: Riluzole

• Other: Placebo (5% glucose water solution)

Phase

2

Outcome measures

Primary outcome measures: Time to death from date of randomisation to date of death.