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.
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
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