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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001327-71 | EudraCT Number |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 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 |
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| 1.0 IL-2 | Experimental | 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 |
|
| 2.0 IL-2 | Experimental | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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). |
| Measure | Description | Time Frame |
|---|---|---|
| CD4+ CD25+ CD127- FoxP3+(Treg) cells: change in percentage of total lymphocytes | Treg refers to regulatory T cells | Day 8 |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Day 1 |
| Presence/absence of specific, pre-defined adverse events. |
| Measure | Description | Time Frame |
|---|---|---|
| Age (years) | Baseline | |
| Sex (male/female) | Baseline | |
| Body mass index (kg/m^2) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Raul Juntas-Morales, MD | CHRU de Montpellier | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| CHRU de Montpellier - Hôpital Gui de Chauliac | Montpellier | 34295 | France |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32651161 | Result | 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. |
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| 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). |
|
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| 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). |
|
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The pre-defined events include: injection site reaction, flu like syndrome, fatigue, gastro-intestinal signs, allergic signs.
| Day 2 |
| 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. | Day 3 |
| 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. | Day 4 |
| 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. | Day 5 |
| 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. | Day 6 |
| 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. | Day 7 |
| 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. | Day 8 |
| 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. | Day 29 |
| 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. | Day 30 |
| 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. | Day 31 |
| 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. | Day 32 |
| 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. | Day 33 |
| 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. | Day 34 |
| 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. | Day 35 |
| 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. | Day 36 |
| 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. | Day 57 |
| 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. | Day 58 |
| 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. | Day 59 |
| 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. | Day 60 |
| 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. | Day 61 |
| 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. | Day 62 |
| 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. | Day 63 |
| 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. | Day 64 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Day 1 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Day 8 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Day 29 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Day 57 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Day 64 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Week 13 |
| Presence/absence of abnormal vital signs | (based on a systematic check of vital signs: pulse, blood pressure, oxymetry, temperature) | Week 25 |
| MedDRA classification of all adverse events throughout the study | MedDRA refers to "Medical Dictionary for Regulatory Activities" | Week 25 |
| Thyroid function: blood T4 | Baseline (day 0 to day -15) |
| Thyroid function: blood T4 | Week 13 |
| Thyroid function: blood TSH | Baseline (day 0 to day -15) |
| Thyroid function: blood TSH | Week 13 |
| Presence/absence of clinically significant abnormality on a lung x-ray | Baseline (day 0 to day -15) |
| Presence/absence of clinically significant abnormality on a lung x-ray | Week 13 |
| Presence/absence of clinically significant abnormality on an electrocardiogram | Baseline (day 0 to day -15) |
| Presence/absence of clinically significant abnormality on an electrocardiogram | Week 13 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Day 1 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Day 8 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Day 29 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Day 57 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Day 64 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Week 13 |
| Presence/absence of a clinically significant abnormality among routine laboratory tests | The routine blood tests considered are:
| Week 25 |
| Vital capacity (% of normal) | This is a measure of respiratory function. | Baseline (day 0 to day -15) |
| Vital capacity (% of normal) | This is a measure of respiratory function. | Day 1 |
| Vital capacity (% of normal) | This is a measure of respiratory function. | Week 13 |
| Vital capacity (% of normal) | This is a measure of respiratory function. | Week 25 |
| The ALSFRS Questionnaire | Day 1 |
| The ALSFRS Questionnaire | Day 29 |
| The ALSFRS Questionnaire | Day 57 |
| The ALSFRS Questionnaire | Week 13 |
| The ALSFRS Questionnaire | Week 25 |
| Tregs (absolute number and % CF4+ cells) | Day 1 |
| Tregs (absolute number and % CF4+ cells) | Day 8 |
| Tregs (absolute number and % CF4+ cells) | Day 57 |
| Tregs (absolute number and % CF4+ cells) | Day 64 |
| Tregs (absolute number and % CF4+ cells) | Week 13 |
| Tregs (absolute number and % CF4+ cells) | Week 25 |
| Total lymphocyte number | Day 1 |
| Total lymphocyte number | Day 8 |
| Total lymphocyte number | Day 57 |
| Total lymphocyte number | Day 64 |
| Total lymphocyte number | Week 13 |
| Total lymphocyte number | Week 25 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | Day 1 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | Day 8 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | Day 57 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | Day 64 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | Week 13 |
| CD56+(NK), CD19+(B), CD3+, CD4+, CD8+ cell populations: numbers and percentages of total lymphocytes | week 25 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Day 1 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Day 8 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Day 57 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Day 64 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Week 13 |
| effector T cells: number and % of CD4 cells | This is measured as CD4+ lymphocytes minus regulatory T cells | Week 25 |
| Phosphorylated neurofilament heavy protein (pNfH) levels in serum | day 1 |
| Light chain neurofilament levels in serum | Day 1 |
| Light chain neurofilament levels in serum | Week 13 |
| Baseline |
| Disease duration from date of first symptoms (fatigue, weakness) | Baseline |
| The patient's current Riluzole posology | Baseline to week 25 |
| The patient's currentposology for other concomitant treatments | Baseline to week 25 |
| Description of concomitant treatments, if any | Throughout study, up to 25 weeks |
| Routine serology results dating to within the last 30 days: HIV-1 (positive/negative ?) | Baseline |
| Routine serology results dating to within the last 30 days: Epstein Barr Virus (positive/negative ?) | Baseline |
| Routine serology results dating to within the last 30 days: cytomegalovirus (positive/negative ?) | Baseline |
| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| C082598 | aldesleukin |
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