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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status
Completed
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Placebo
1.0 MIU IL-2 per day
2.0 MIU IL-2 per day
Sponsored by
Centre Hospitalier Universitaire de Nīmes
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring low-dose interleukin 2

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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)

Sites / Locations

  • CHRU de Montpellier - Hôpital Gui de Chauliac

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Placebo Comparator

Experimental

Experimental

Arm Label

Placebo

1.0 IL-2

2.0 IL-2

Arm 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

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

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

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of specific, pre-defined adverse events.
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Presence/absence of abnormal vital signs
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
MedDRA classification of all adverse events throughout the study
MedDRA refers to "Medical Dictionary for Regulatory Activities"
Thyroid function: blood T4
Thyroid function: blood T4
Thyroid function: blood TSH
Thyroid function: blood TSH
Presence/absence of clinically significant abnormality on a lung x-ray
Presence/absence of clinically significant abnormality on a lung x-ray
Presence/absence of clinically significant abnormality on an electrocardiogram
Presence/absence of clinically significant abnormality on an electrocardiogram
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration ) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Presence/absence of a clinically significant abnormality among routine laboratory tests
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Vital capacity (% of normal)
This is a measure of respiratory function.
Vital capacity (% of normal)
This is a measure of respiratory function.
Vital capacity (% of normal)
This is a measure of respiratory function.
Vital capacity (% of normal)
This is a measure of respiratory function.
The ALSFRS Questionnaire
The ALSFRS Questionnaire
The ALSFRS Questionnaire
The ALSFRS Questionnaire
The ALSFRS Questionnaire
Tregs (absolute number and % CF4+ cells)
Tregs (absolute number and % CF4+ cells)
Tregs (absolute number and % CF4+ cells)
Tregs (absolute number and % CF4+ cells)
Tregs (absolute number and % CF4+ cells)
Tregs (absolute number and % CF4+ cells)
Total lymphocyte number
Total lymphocyte number
Total lymphocyte number
Total lymphocyte number
Total lymphocyte number
Total lymphocyte number
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
effector T cells: number and % of CD4 cells
This is measured as CD4+ lymphocytes minus regulatory T cells
Phosphorylated neurofilament heavy protein (pNfH) levels in serum
Light chain neurofilament levels in serum
Light chain neurofilament levels in serum

Full Information

First Posted
February 7, 2014
Last Updated
May 30, 2016
Sponsor
Centre Hospitalier Universitaire de Nīmes
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1. Study Identification

Unique Protocol Identification Number
NCT02059759
Brief Title
Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2
Acronym
IMODALS
Official Title
Immuno-modulation in Amyotrophic Lateral Sclerosis- a Phase II Study of Safety and Activity of Low Dose Interleukin-2
Study Type
Interventional

2. Study Status

Record Verification Date
May 2016
Overall Recruitment Status
Completed
Study Start Date
September 2015 (undefined)
Primary Completion Date
December 2015 (Actual)
Study Completion Date
May 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Centre Hospitalier Universitaire de Nīmes

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyotrophic Lateral Sclerosis
Keywords
low-dose interleukin 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
36 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm 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
Arm Title
1.0 IL-2
Arm Type
Experimental
Arm 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
Arm Title
2.0 IL-2
Arm Type
Experimental
Arm 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
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention 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 Type
Drug
Intervention Name(s)
1.0 MIU IL-2 per day
Other Intervention Name(s)
Aldesleukine, Proleukin
Intervention 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 Type
Drug
Intervention Name(s)
2.0 MIU IL-2 per day
Other Intervention Name(s)
Aldesleukine, Proleukin
Intervention 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).
Primary Outcome Measure Information:
Title
CD4+ CD25+ CD127- FoxP3+(Treg) cells: change in percentage of total lymphocytes
Description
Treg refers to regulatory T cells
Time Frame
Day 8
Secondary Outcome Measure Information:
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 1
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 2
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 3
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 4
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 5
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 6
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 7
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 8
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 29
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 30
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 31
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 32
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 33
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 34
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 35
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 36
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 57
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 58
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 59
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 60
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 61
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 62
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 63
Title
Presence/absence of specific, pre-defined adverse events.
Description
The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
Time Frame
Day 64
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Day 1
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Day 8
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Day 29
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Day 57
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Day 64
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Week 13
Title
Presence/absence of abnormal vital signs
Description
(based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)
Time Frame
Week 25
Title
MedDRA classification of all adverse events throughout the study
Description
MedDRA refers to "Medical Dictionary for Regulatory Activities"
Time Frame
Week 25
Title
Thyroid function: blood T4
Time Frame
Baseline (day 0 to day -15)
Title
Thyroid function: blood T4
Time Frame
Week 13
Title
Thyroid function: blood TSH
Time Frame
Baseline (day 0 to day -15)
Title
Thyroid function: blood TSH
Time Frame
Week 13
Title
Presence/absence of clinically significant abnormality on a lung x-ray
Time Frame
Baseline (day 0 to day -15)
Title
Presence/absence of clinically significant abnormality on a lung x-ray
Time Frame
Week 13
Title
Presence/absence of clinically significant abnormality on an electrocardiogram
Time Frame
Baseline (day 0 to day -15)
Title
Presence/absence of clinically significant abnormality on an electrocardiogram
Time Frame
Week 13
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration ) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Day 1
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Day 8
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Day 29
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Day 57
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Day 64
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Week 13
Title
Presence/absence of a clinically significant abnormality among routine laboratory tests
Description
The routine blood tests considered are: haemogram (hemoglobin, hematocrit, red blood cell count, white blood cell count, leukocyte formula, platelets, mean corpuscular volume, mean corpuscular hemoglobin, mean corpuscular hemoglobin concentration) blood biochemistry (ionogram, urea, creatinine, glucose, C reactive protein, procalcitonin, protein, albumin) liver function panel (aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, bilirubin) iron metabolism (iron, ferritin, transferrin)
Time Frame
Week 25
Title
Vital capacity (% of normal)
Description
This is a measure of respiratory function.
Time Frame
Baseline (day 0 to day -15)
Title
Vital capacity (% of normal)
Description
This is a measure of respiratory function.
Time Frame
Day 1
Title
Vital capacity (% of normal)
Description
This is a measure of respiratory function.
Time Frame
Week 13
Title
Vital capacity (% of normal)
Description
This is a measure of respiratory function.
Time Frame
Week 25
Title
The ALSFRS Questionnaire
Time Frame
Day 1
Title
The ALSFRS Questionnaire
Time Frame
Day 29
Title
The ALSFRS Questionnaire
Time Frame
Day 57
Title
The ALSFRS Questionnaire
Time Frame
Week 13
Title
The ALSFRS Questionnaire
Time Frame
Week 25
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Day 1
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Day 8
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Day 57
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Day 64
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Week 13
Title
Tregs (absolute number and % CF4+ cells)
Time Frame
Week 25
Title
Total lymphocyte number
Time Frame
Day 1
Title
Total lymphocyte number
Time Frame
Day 8
Title
Total lymphocyte number
Time Frame
Day 57
Title
Total lymphocyte number
Time Frame
Day 64
Title
Total lymphocyte number
Time Frame
Week 13
Title
Total lymphocyte number
Time Frame
Week 25
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
Day 1
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
Day 8
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
Day 57
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
Day 64
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
Week 13
Title
CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes
Time Frame
week 25
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Day 1
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Day 8
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Day 57
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Day 64
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Week 13
Title
effector T cells: number and % of CD4 cells
Description
This is measured as CD4+ lymphocytes minus regulatory T cells
Time Frame
Week 25
Title
Phosphorylated neurofilament heavy protein (pNfH) levels in serum
Time Frame
day 1
Title
Light chain neurofilament levels in serum
Time Frame
Day 1
Title
Light chain neurofilament levels in serum
Time Frame
Week 13
Other Pre-specified Outcome Measures:
Title
Age (years)
Time Frame
Baseline
Title
Sex (male/female)
Time Frame
Baseline
Title
Body mass index (kg/m^2)
Time Frame
Baseline
Title
Disease duration from date of first symptoms (fatigue, weakness)
Time Frame
Baseline
Title
The patient's current Riluzole posology
Time Frame
Baseline to week 25
Title
The patient's currentposology for other concomitant treatments
Time Frame
Baseline to week 25
Title
Description of concomitant treatments, if any
Time Frame
Throughout study, up to 25 weeks
Title
Routine serology results dating to within the last 30 days: HIV-1 (positive/negative ?)
Time Frame
Baseline
Title
Routine serology results dating to within the last 30 days: Epstein Barr Virus (positive/negative ?)
Time Frame
Baseline
Title
Routine serology results dating to within the last 30 days: cytomegalovirus (positive/negative ?)
Time Frame
Baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Raul Juntas-Morales, MD
Organizational Affiliation
CHRU de Montpellier
Official's Role
Study Director
Facility Information:
Facility Name
CHRU de Montpellier - Hôpital Gui de Chauliac
City
Montpellier
ZIP/Postal Code
34295
Country
France

12. IPD Sharing Statement

Citations:
PubMed Identifier
32651161
Citation
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.
Results Reference
derived

Learn more about this trial

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

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