immuno-modulation in amyotrophic lateral sclerosis- a phase ii study of safety and activity of low dose interleukin-2

Conditions: Amyotrophic Lateral Sclerosis

Summary: 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)

Keywords: low-dose interleukin 2