MIROCALS: Modifying Immune Response and OutComes in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

— MIROCALS  

Official title:

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 Randomized, Double-blind, Placebo- Controlled, Phase-II Proof of Concept/ Proof of Mechanism Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03039673
• Other study ID #: H2020/PHRC-N/2014/GB-01
• Secondary ID: No 633413PHRC-N,
• Status: Completed
• Phase: Phase 2
• Start date: June 19, 2017
• Est. completion date: July 22, 2021

Study information

• Verified date: April 2022
• Source: Centre Hospitalier Universitaire de Nimes
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 304
• Est. completion date: July 22, 2021
• Est. primary completion date: July 22, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Main 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

Main 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

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease
• Sclerosis

Intervention

Drug:
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
France	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	APHP - Groupe Hospitalier Pitié-Salpetrière	Paris Cedex 13
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
United Kingdom	Trafford Centre for Biomedical Research	Brighton
United Kingdom	Institute of Neurological Sciences, Queen Elizabeth University Hospital	Glasgow
United Kingdom	Centre for Neuromuscular Diseases - National Hospital of Neurology	London
United Kingdom	King's MND Care and Research Centre	London
United Kingdom	North-East London and Essex MND Regional Care Centre	London
United Kingdom	Salford Royal NHS Foundation Trust, Neurology Dept	Manchester
United Kingdom	Sheffield Care and Research Centre	Sheffield

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier Universitaire de Nimes

Countries where clinical trial is conducted

France,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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