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

NCT ID: NCT02059759

Last Updated: 2025-11-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 36 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-09-30
• Study Completion Date: 2016-05-25

Brief 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.

Detailed 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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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 IL-2

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

Group Type: EXPERIMENTAL

1.0 MIU IL-2 per day

Intervention Type: DRUG

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 IL-2

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

Group Type: EXPERIMENTAL

2.0 MIU IL-2 per day

Intervention Type: DRUG

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).

Interventions

Placebo

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 Type: DRUG

1.0 MIU IL-2 per day

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 Type: DRUG

2.0 MIU IL-2 per day

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 Type: DRUG

Other Intervention Names

Aldesleukine; Proleukin; Aldesleukine; Proleukin

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)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Nīmes

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Raul Juntas-Morales, MD

Role: STUDY_DIRECTOR

CHRU de Montpellier

Locations

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, , France

Countries

France

References

Camu W, Mickunas M, Veyrune JL, Payan C, Garlanda C, Locati M, Juntas-Morales R, Pageot N, Malaspina A, Andreasson U, Kirby J, Suehs C, Saker S, Masseguin C, De Vos J, Zetterberg H, Shaw PJ, Al-Chalabi A, Leigh PN, Tree T, Bensimon G. Repeated 5-day cycles of low dose aldesleukin in amyotrophic lateral sclerosis (IMODALS): A phase 2a randomised, double-blind, placebo-controlled trial. EBioMedicine. 2020 Sep;59:102844. doi: 10.1016/j.ebiom.2020.102844. Epub 2020 Jul 7.

Reference Type: RESULT

PMID: 32651161 (View on PubMed)

Other Identifiers

2014-001327-71

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

LOCAL/2014/WC-01

Identifier Type: -

Identifier Source: org_study_id