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

Centre Hospitalier Universitaire de Nīmes

Status and phase: Completed; Phase 2

Conditions: Amyotrophic Lateral Sclerosis

Treatments: Drug: 2.0 MIU IL-2 per day; Drug: 1.0 MIU IL-2 per day; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02059759

2014-001327-71 (EudraCT Number)

LOCAL/2014/WC-01

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 36 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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36 participants in 3 patient groups, including a placebo group

Placebo

Placebo Comparator group

Description:

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). Intervention: Placebo

Treatment:

Drug: Placebo

1.0 IL-2

Experimental group

Description:

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). Intervention: 1.0 MIU IL-2 per day

Treatment:

Drug: 1.0 MIU IL-2 per day

2.0 IL-2

Experimental group

Description:

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). Intervention: 2.0 MIU IL-2 per day

Treatment:

Drug: 2.0 MIU IL-2 per day