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

Phase 1

Conditions: Amyotrophic Lateral Sclerosis (ALS)
MedDRA version: 20.0Level: PTClassification code 10002026Term: Amyotrophic lateral sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2015-005347-14-GB

Lead Sponsor: CHU DE NIMES

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 216

Inclusion Criteria

Inclusion criteria for the persons taking part in the trial
1 / Run-in period
•The patient has been correctly informed
•The patient must have given his/her informed and signed consent.
•The patient must be 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 (ie. less than 4 weeks/ 28 days) or current riluzole treatment; when riluzole treatment is present and the prior duration of treatment is less than or equal to 4 weeks (28 days), a riluzole wash-out period of at least 4 weeks (28 days) must be performed prior to entry.
•Lumbar punctures accepted by patient and feasible

2/ Randomised controlled trial period
•Run-in period completed, including lumbar puncture and sampling for blood biomarkers at inclusion and at 3 months
•The patient is willing to continue participation
•Disease duration = 28 months
•Stable dose of riluzole treatment for at least 3 months

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 54
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 162

Exclusion Criteria

Exclusion criteria for persons taking part in the trial (run-in and Randomised Control Trial periods)
•The patient is participating in another research study that may interfere with the results or conclusions of this study
•Within the past three months, the patient has participated in another study that may interfere with the results or conclusions of this study
•The patient is in an exclusion period determined by a previous study
•The patient does not have capacity to give fully informed consent and/or to comply with study requirements and procedures
•Significant cognitive impairment as judged by investigator on the basis of his/her assessment of the patient, taking into account information from caregivers
•Other neurodegenerative disease that could explain signs or symptoms
•Contra indication for lumbar puncture (presence of contra-indicated treatment, –see section 11.3.2, or coagulation test abnormality, clinically significant coagulopathy or thrombocytopenia)
•Non authorised treatment (see section 11.3 of the protocol)
•Other disease or disorders that could preclude functional assessments or life-threatening disorders
•Any Cancer within the past 5 years (except stable non-metastatic basal cell skin carcinoma or in situ carcinoma of the cervix)
•Severe cardiac or pulmonary disease
•Any documented, active, past or present ,auto-immune disorders except asymptomatic Hashimoto thyroiditis
•Using assisted ventilation
•Gastrostomy
•Women of child-bearing age and sexually active men without effective contraception or woman who are pregnant or breast feeding
•Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride and glucose).
•Clinically significant evidence of active viral infection at randomisation: CMV, EBV, HIV-1, HBV or HCV
•History of documented symptomatic and treated asthma within the past 5 years

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: The main Objective is 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 rate of ALS disease progression.;Secondary Objective: The secondary Objectives are:<br>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).<br>The aims of this new trial design are:<br>(i) To shorten future trials duration in ALS using an early drug responding surrogate marker of disease activity;<br>(ii) To establish the proof of mechanism (PoM) of the tested drugs;<br>(iii) To identify drug responder status.<br>;Primary end point(s): Survival from randomisation to date of death from any cause or date of end of study ;Timepoint(s) of evaluation of this end point: 548 days

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): A.Secondary clinical efficacy : <br>A.1 ALSFRSr; <br>A.2 Slow Vital Capacity; <br>A.3 QoL EuroQL5D, <br>A.4 ECAS<br>B.Secondary laboratory efficacy <br>B.1 Immuno-cytometry: Tregs (CD4+CD25+CD127-FOXP3+), Total Lymphocytes, CD3+, CD4+, CD8+ , NK (CD3-CD56+), B(CD19<br>B.2 pNFH and CCL2 levels (CSF and Blood)<br>;Timepoint(s) of evaluation of this end point: A.Secondary clinical efficacy : <br>A.1 monthly<br>A.2 6-monthly <br>A.3 6-monthly<br>A.4 at inclusion and at month 4<br>B.Secondary laboratory efficacy <br>B.1 at Inclusion, Randomisation, D8, D113 and D120<br>B.2 pNFH and CCL2 levels (Blood) at Inclusion,Randomisation, D8, D113 and D120, pNFH and CCL2 levels (CSF)at Inclusion, Randomisation and D113