Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2

The primary objective is to evaluate in ALS patients the regulatory T cell early response to two low-doses of IL-2 at 1 and 2 MIU per day after one course of 5 consecutive days comparatively to placebo.

This is a phase II study on ld-IL-2 as a therapeutic agent for ALS which aims at defining the activity and safety of a range a doses for subsequent use of the best dose in a phase II/III trial. For ethical reasons, ld-IL-2 must be tested as an add-on therapy to riluzole hence all patients will need to be treated with riluzole for at least three months prior to entry. A randomized (1:1:1), placebo-controlled, double-blind, parallel group trial will be carried out to assess ld-IL-2 activity on regulatory T cells and immuno-inflammatory markers in ALS patients treated for 3 months (5 days every four weeks repeated three times).

The secondary objectives of this study are:

A. To evaluate maintenance of Tcell response after three repeated 5-day courses at one course every four weeks for 12 weeks.

B. To evaluate the safety of ld-IL-2 therapy in an ALS population, with an overall follow-up of 6 months (up to 15 weeks after last administration); C. To evaluate functional changes throughout the study; D. To evaluate changes in other pre-defined blood cytology parameters, and a blood biomarker for axonal damage.

Eligibility Criteria:
Inclusion Criteria:

* The patient has been correctly informed
* The patient must have given his/her informed and signed consent.
* The patient must be insured or beneficiary of a health insurance plan.
* The patient is at least 18 years old and less than 75 years old
* Probable, or laboratory-supported probable or definite ALS as defined by El Escorial Revised ALS diagnostic criteria (according to Airlie House Conference 1988)
* Stable on riluzole treatment for more than 3 months with liver function test results \< 2ULN
* Disease duration ≤ 5 years
* Vital capacity ≥ 70% of normal
* Ability to swallow without the requirement for nasogastric or PEG feeding
* Agreement for patient to use an adequate method of contraception throughout the study and for 2 weeks after post study visit
* The patient is available and willing to participate in seven study visits occurring at the CHU within the next six months

Exclusion Criteria:

* The patient is participating in another interventional study
* Within the past three months, the patient has participated in another interventional
* The patient is in an exclusion period determined by a previous study
* The patient is under judicial protection
* The patient is an adult under guardianship
* The patient refuses to sign the consent
* It is impossible to correctly inform the patient
* Other life threatening disease
* Presence of contra-indicated concomitant treatments or with potential neuroprotective benefit (see section 11.2 of the protocol)
* Presence of tracheostomy or non-invasive ventilation
* Use of Percutaneous endoscopic gastrostomy (PEG) or nasogastric tube
* Presence of clinical infection (treated or untreated)
* Positive serology for CMV, EBV (confirmed by viral load), or HIV
* Vaccination within 8 weeks prior to first experimental dosing
* Other disease precluding functional assessments
* 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
* Documented auto-immune disorders except asymptomatic Hashimoto thyroiditis
* Women of child bearing age without contraception or pregnant or breast feeding
* Any clinically significant laboratory abnormality (excepting cholesterol, triglyceride and glucose)