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

Phase 2CompletedNCT02059759

Centre Hospitalier Universitaire de Nīmes36 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

Conditions

Amyotrophic Lateral Sclerosis

Interventions

PlaceboDRUG

Patients in this arm will receive sub-cutaneous injections of placebo (same vehicle as for experimental arms, and same volume) for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).

1.0 MIU IL-2 per dayDRUG

Patients in this arm will receive sub-cutaneous injections corresponding to 1.0 MIU of IL-2 per injection for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).

2.0 MIU IL-2 per dayDRUG

Patients in this arm will receive sub-cutaneous injections corresponding to 2.0 MIU of IL-2 per injection for 5 consecutive days at the beginning of three consecutive months (a total of 15 injections, 5 per month for 3 months).

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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)

Locations (1)

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, France

Outcomes

Primary Outcomes

CD4+ CD25+ CD127- FoxP3+(Treg) cells: change in percentage of total lymphocytes

Treg refers to regulatory T cells

Time frame: Day 8