Clinical trial NCT03039673: MIROCALS: Modifying Immune Response and OutComes in ALS
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: interleukin-2
low-dose interleukin-2
Lead sponsor: Centre Hospitalier Universitaire de Nīmes
Sponsor class: OTHER
First posted: 2017-02-01
Enrollment: 304
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

Eligibility criteria: 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

Primary outcomes:
measure: Time to death from date of randomization to date of death
timeFrame: Month 21
Secondary outcomes:
Other outcomes:
Locations:
city: Lille
country: France
facility: CHRU de Lille - Hôpital Roger Salengro
city: Limoges
country: France
facility: CHU de Limoges - Hôpital Dupuytren
city: Lyon
country: France
facility: HCL - Hôpital Neurologique P. Wertheimer
city: Marseille
country: France
facility: APHM - Hôpital de la Timone
city: Montpellier Cedex 5
country: France
facility: CHRU de Montpellier - Hôpital Gui de Chauliac
city: Nice
country: France
facility: CHU de Nice - Hôpital Pasteur
city: Paris Cedex 13
country: France
facility: APHP - Groupe Hospitalier Pitié-Salpetrière
city: Saint Brieuc
country: France
facility: CENTRE HOSPITALIER DE SAINT BRIEUC - Hôpital Yves Le Foll
city: Strasbourg
country: France
facility: CHU de Strasbourg - Hôpital de Hautepierre
city: Tours
country: France
facility: CHRU de Tours - Hôpital Bretonneau
city: Brighton
country: United Kingdom
facility: Trafford Centre for Biomedical Research
city: Glasgow
country: United Kingdom
facility: Institute of Neurological Sciences, Queen Elizabeth University Hospital
city: London
country: United Kingdom
facility: North-East London and Essex MND Regional Care Centre
city: London
country: United Kingdom
facility: King's MND Care and Research Centre
city: London
country: United Kingdom
facility: Centre for Neuromuscular Diseases - National Hospital of Neurology
city: Manchester
country: United Kingdom
facility: Salford Royal NHS Foundation Trust, Neurology Dept
city: Sheffield
country: United Kingdom
facility: Sheffield Care and Research Centre
Study officials:
affiliation: Brighton and Sussex Medical School
name: Nigel Leigh, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Centre Hospitalier Universitaire de Nîmes
name: Gilbert Bensimon, MD, PhD
role: STUDY_DIRECTOR
References: