Skip to main content
OpenTrials
Completed

NCT Number: NCT02059759

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Amyotrophic Lateral Sclerosis Central Nervous System Diseases Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Spinal Cord Diseases TDP-43 Proteinopathies

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

CHRU de Montpellier - Hôpital Gui de Chauliac

Montpellier, 34295, France

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Placebo

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 MIU IL-2 per day

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).

Other names: Aldesleukine, Proleukin

2.0 MIU IL-2 per day

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).

Other names: Aldesleukine, Proleukin

Primary outcomes

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

    Time frame: Day 8

    Treg refers to regulatory T cells

Secondary outcomes

  1. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 1

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  2. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 2

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  3. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 3

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  4. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 4

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  5. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 5

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  6. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 6

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  7. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 7

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  8. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 8

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  9. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 29

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  10. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 30

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  11. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 31

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  12. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 32

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  13. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 33

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  14. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 34

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  15. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 35

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  16. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 36

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  17. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 57

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  18. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 58

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  19. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 59

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  20. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 60

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  21. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 61

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  22. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 62

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  23. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 63

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  24. Presence/absence of specific, pre-defined adverse events.

    Time frame: Day 64

    The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.

  25. Presence/absence of abnormal vital signs

    Time frame: Day 1

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  26. Presence/absence of abnormal vital signs

    Time frame: Day 8

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  27. Presence/absence of abnormal vital signs

    Time frame: Day 29

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  28. Presence/absence of abnormal vital signs

    Time frame: Day 57

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  29. Presence/absence of abnormal vital signs

    Time frame: Day 64

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  30. Presence/absence of abnormal vital signs

    Time frame: Week 13

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  31. Presence/absence of abnormal vital signs

    Time frame: Week 25

    (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature)

  32. MedDRA classification of all adverse events throughout the study

    Time frame: Week 25

    MedDRA refers to "Medical Dictionary for Regulatory Activities"

  33. Thyroid function: blood T4

    Time frame: Baseline (day 0 to day -15)

  34. Thyroid function: blood T4

    Time frame: Week 13

  35. Thyroid function: blood TSH

    Time frame: Baseline (day 0 to day -15)

  36. Thyroid function: blood TSH

    Time frame: Week 13

  37. Presence/absence of clinically significant abnormality on a lung x-ray

    Time frame: Baseline (day 0 to day -15)

  38. Presence/absence of clinically significant abnormality on a lung x-ray

    Time frame: Week 13

  39. Presence/absence of clinically significant abnormality on an electrocardiogram

    Time frame: Baseline (day 0 to day -15)

  40. Presence/absence of clinically significant abnormality on an electrocardiogram

    Time frame: Week 13

  41. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Day 1

    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)

  42. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Day 8

    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)

  43. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Day 29

    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)

  44. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Day 57

    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)

  45. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Day 64

    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)

  46. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Week 13

    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)

  47. Presence/absence of a clinically significant abnormality among routine laboratory tests

    Time frame: Week 25

    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)

  48. Vital capacity (% of normal)

    Time frame: Baseline (day 0 to day -15)

    This is a measure of respiratory function.

  49. Vital capacity (% of normal)

    Time frame: Day 1

    This is a measure of respiratory function.

  50. Vital capacity (% of normal)

    Time frame: Week 13

    This is a measure of respiratory function.

  51. Vital capacity (% of normal)

    Time frame: Week 25

    This is a measure of respiratory function.

  52. The ALSFRS Questionnaire

    Time frame: Day 1

  53. The ALSFRS Questionnaire

    Time frame: Day 29

  54. The ALSFRS Questionnaire

    Time frame: Day 57

  55. The ALSFRS Questionnaire

    Time frame: Week 13

  56. The ALSFRS Questionnaire

    Time frame: Week 25

  57. Tregs (absolute number and % CF4+ cells)

    Time frame: Day 1

  58. Tregs (absolute number and % CF4+ cells)

    Time frame: Day 8

  59. Tregs (absolute number and % CF4+ cells)

    Time frame: Day 57

  60. Tregs (absolute number and % CF4+ cells)

    Time frame: Day 64

  61. Tregs (absolute number and % CF4+ cells)

    Time frame: Week 13

  62. Tregs (absolute number and % CF4+ cells)

    Time frame: Week 25

  63. Total lymphocyte number

    Time frame: Day 1

  64. Total lymphocyte number

    Time frame: Day 8

  65. Total lymphocyte number

    Time frame: Day 57

  66. Total lymphocyte number

    Time frame: Day 64

  67. Total lymphocyte number

    Time frame: Week 13

  68. Total lymphocyte number

    Time frame: Week 25

  69. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: Day 1

  70. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: Day 8

  71. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: Day 57

  72. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: Day 64

  73. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: Week 13

  74. CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes

    Time frame: week 25

  75. effector T cells: number and % of CD4 cells

    Time frame: Day 1

    This is measured as CD4+ lymphocytes minus regulatory T cells

  76. effector T cells: number and % of CD4 cells

    Time frame: Day 8

    This is measured as CD4+ lymphocytes minus regulatory T cells

  77. effector T cells: number and % of CD4 cells

    Time frame: Day 57

    This is measured as CD4+ lymphocytes minus regulatory T cells

  78. effector T cells: number and % of CD4 cells

    Time frame: Day 64

    This is measured as CD4+ lymphocytes minus regulatory T cells

  79. effector T cells: number and % of CD4 cells

    Time frame: Week 13

    This is measured as CD4+ lymphocytes minus regulatory T cells

  80. effector T cells: number and % of CD4 cells

    Time frame: Week 25

    This is measured as CD4+ lymphocytes minus regulatory T cells

  81. Phosphorylated neurofilament heavy protein (pNfH) levels in serum

    Time frame: day 1

  82. Light chain neurofilament levels in serum

    Time frame: Day 1

  83. Light chain neurofilament levels in serum

    Time frame: Week 13

Other outcomes

  1. Age (years)

    Time frame: Baseline

  2. Sex (male/female)

    Time frame: Baseline

  3. Body mass index (kg/m^2)

    Time frame: Baseline

  4. Disease duration from date of first symptoms (fatigue, weakness)

    Time frame: Baseline

  5. The patient's current Riluzole posology

    Time frame: Baseline to week 25

  6. The patient's currentposology for other concomitant treatments

    Time frame: Baseline to week 25

  7. Description of concomitant treatments, if any

    Time frame: Throughout study, up to 25 weeks

  8. Routine serology results dating to within the last 30 days: HIV-1 (positive/negative ?)

    Time frame: Baseline

  9. Routine serology results dating to within the last 30 days: Epstein Barr Virus (positive/negative ?)

    Time frame: Baseline

  10. Routine serology results dating to within the last 30 days: cytomegalovirus (positive/negative ?)

    Time frame: Baseline

Sponsors and collaborators

Lead sponsor

Centre Hospitalier Universitaire de Nīmes

Other

Registry information

Acronym: IMODALS

Important dates

Study start
2015
Primary completion
2016
Study completion
2016
First posted
Feb 11, 2014
Registry last updated
Nov 17, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.