COVID 19Phase 2LILIADE-COVIDNCT04357444
Low Dose of IL-2 In Acute Respiratory DistrEss Syndrome Related to COVID-19
A Phase 2 study testing 1: ILT101 in people with COVID 19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
The purpose is to demonstrate the efficacy of low-dose interleukin 2 (Ld-IL2) administration in improving clinical course and oxygenation parameters in patients with SARS-CoV2-related ARDS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID 19
- What is being tested?
- 1: ILT101
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteFrance
- Study dates
- 23 Oct 2020to 5 Apr 2021
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, age ≥ 18 years
- Laboratory (RT-PCR) confirmed infection with SARS-CoV2
- Patient is either under invasive or non-invasive mechanical ventilation (including high flow nasal oxygen therapy).
- Diagnosis of ARDS according to the Berlin definition of ARDS
- Onset of ARDS <96 hours
- Patient with French Social Security System
- A written informed consent by the designated substitute decision maker, if present. In the event of absence, the patient can be included by investigator's decision alone.
Who cannot join
- Previous history of ARDS in the last month
- Chronic respiratory diseases requiring long-term oxygen therapy and/or long-term respiratory assistance
- History of organ allograft.
- Active cancer
- Liver cirrhosis with basal Child and Pugh of C
- Pulmonary fibrosis
Show all 20Show fewer
- Patient with end-of-life decision
- Patient not expected to survive for 24 hours
- Woman known to be pregnant, lactating or with a positive (urine or serum test) or indeterminate (serum test) pregnancy test
- Patient already enrolled in another interventional pharmacotherapy protocol on COVID-19
- Patient with known hypersensitivity to natural or recombinant Interleukin-2 or to any of the excipients
- Presence of any of the following abnormal laboratory values at screening: absolute neutrophil count (ANC) less than 1.5x109/L, AST or ALT greater than 5 x ULN, platelets <50,000 per mm3
- Use of chronic oral corticosteroids > 10 mg prednisone equivalent a day for a non-COVID-19-related condition
- Current uncontrolled autoimmune disease
- Patients with uncontrolled suspected or known active systemic bacterial or fungal infections
- Patient with severe, uncontrolled pre-existing (chronic) organ failure (myocardial, hepatic or renal)
- Vaccination with live attenuated vaccines in the month preceding the inclusion
- Patient with burns to ≥ 15% of their total body surface area
- Patient receiving extra-corporeal membrane oxygenation, high-frequency oscillatory ventilation or any form of extra-corporeal lung support
- Patient under legal protection (protection of the court, or in curatorship or guardianship).
Trial locations and contacts
1 site in 1 country.
France1 site
Service Anesthésie Réanimation - Groupe Hospitalier Pitié-Salpêtrière
Paris, 75013
About this study
The purpose is to demonstrate the efficacy of low-dose interleukin 2 (Ld-IL2) administration in improving clinical course and oxygenation parameters in patients with SARS-CoV2-related ARDS.
Read the detailed description
About 25% of hospitalized patients with SARS-CoV2 infection presented life-threatening respiratory conditions. Of these, 60% met ARDS criteria leading to death in 25% to 63% of the cases. SARS-CoV2-related ARDS is caused by a massive inflammatory cell infiltration leading to dysregulated cytokine/chemokine responses with lung immunopathological changes. To date, there is no treatment available.
Regulatory T cells (Treg) are a subpopulation of CD4+ T cells playing a crucial role in the control of immune responses, in part by preventing excessive inflammation. Depletion of Treg cells in models of lung infection or after berylium exposure exacerbated lung inflammation. In contrast, a beneficial role for Treg during early ARDS and its resolution has been observed.
Low-dose interleukin 2 (Ld-IL2) is the first therapy driving Treg-specific expansion and activation. Ld-IL2 was successfully tested in a wide range of preclinical models of inflammatory diseases, including beryllium-induced lung inflammation. Moreover, Ld-IL2 has been shown to be safe and free of serious adverse events when administered in patients with various autoimmune diseases. Importantly, in our previous work, we observed only very low concentrations of IL-2 in the blood (0.1 pg/mL [0.0-2.0]) as well as in the BAL supernatant (0.8 pg/mL [0.4-1.3]) collected from patients during the early phase of ARDS, suggesting that additional IL-2 could be beneficial for Treg expansion/activation.
Our objective is therefore to investigate the therapeutic benefit of Ld-IL2 as a Treg inducer for controlling SARS-CoV2-related ARDS.
After admission of patients to the intensive care unit at one of the recruiting centers, the eligibility criteria will be checked by the investigating physician and participation in the study will be proposed to the patient or parent/family member/trusted person. If the patient is unable to consent and there is no parent/family member/trusted person, the patient may be included in the emergency procedure.
After inclusion (J0), the patient will be randomized to one of the 2 treatment arms (low dose IL-2 or placebo).
The experimental treatment will be daily administered to the patient from D1 to D10.
The patient will be monitored daily until D28 during hospitalization.
- Conditions
- COVID 19
- Being tested
- 1: ILT101, 2: Placebo Comparator
- Keywords
- COVID-19, SARS-CoV2, Acute Respiratory Distress Syndrome, Low dose of IL-2, Immunotherapy
- Medical subject headings
- COVID-19, Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1: ILT101Drug
Subcutaneous injections, once-daily administration for 10 consecutive days.
2: Placebo ComparatorDrug
placebo in Subcutaneous route
| Study group | Role | What they receive |
|---|---|---|
| 1: ILT101 | Experimental | ILT-101 in Subcutaneous route Receives: Drug: 1: ILT101 |
| 2: Placebo Comparator | Placebo comparator | Placebo in subcutaneous injections every day during 10 days Receives: Drug: 2: Placebo Comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
The PaO2/FiO2 ratio at D11
Measured: at Day11
Secondary outcomes (19)
Changes in Tregs between Baseline and Day 7 (expressed in %)
Measured: at Day0 and Day7
Number of days alive with oxygen therapy within 28 days
Measured: at Day28
Maximal oxygen rate within 28 days
Measured: at Day28
Number of days alive free of invasive or non-invasive ventilation within 28 days
Measured: At Day28
Number of days alive outside ICU within 28 days
Measured: at Day28
Number of days alive outside hospital within 28 days
Measured: at Day28
Time (in days) from randomization to death
Measured: through study completion at day 28
Mortality rate at D28
Measured: at Day28
Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7)
Measured: at Day0 and Day7 or at the time of discharge
Use of antibiotics for respiratory (proved or suspected) infection within 28 days
Measured: at Day28
Number of prone positioning sessions
Measured: throughout the follow up period at day 28
Changes in Tregs during the different visits between baseline and day 28
Measured: at Day0, 5, 7, 11, 14 and Day28
Cytokines analysis on plasma samples at Day 0, 7 and 14
To evaluate selected immune and inflammatory markers: Serum concentrations of cytokines and soluble factors related to the immune response and inflammatory processes will be evaluated and compare to baseline by multiplex immunoprofiling to analyse a larger number of molecules including at least IFNα2, IFNγ, IL-1α, IL-1β, IL-1RA, IL-2, IL-6, IL-8, IL-10, IL-17, TNFα, TNFβ, VEGF-A, TGF-beta, S-RAGE, SP-A, SP-D, Angiopoétine 1 and KGF.
Measured: at Day 0, 7 and 14
Tregs numbers during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.
Measured: at Day0, 5, 7, 11, 14 and Day28
Tregs percentages during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.
Measured: at Day0, 5, 7, 11, 14 and Day28
Deep Immunophenotyping of Cellular components in blood samples at Day 0, 7, and 14
Cellular components will be analysed by flow cytometry covering (i) most of the innate and adaptive immune cells including Tregs, T helper cell subsets including follicular helper cells, B cell subsets, NK cell subsets, (ii) the associated relevant markers of activation/function/differentiation, tissue migration, as well as (iii) unconventional lymphoid cells (NKT/MAIT, innate lymphoid cells), myeloid-derived suppressor cells, classical and non-classical monocytes and dendritic cells (mDC1/2, pDC).
Measured: at Day0, 7 and Day14
T cell repertoire on Treg, after sorting from blood at Day 7 and Day 14 and compared to baseline
Measured: at Day0, 7 and Day14
T cell repertoire on Teff (CD4 and CD8) after sorting from blood at Day 7 and Day 14 and compared to baseline
Measured: at Day0, 7 and Day14
Single cells sequencing will be performed in BAL at Day 7 and Day 14 and compared to baseline.
Measured: at Day0, 7 and Day14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Apr 2020
- Study start23 Oct 2020
- Primary completion2 Nov 2020
- Study completion5 Apr 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COVID 19Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Iltoo Pharma
- Responsible party
- Sponsor
- Investigators
- Jean-Michel CONSTANTIN, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04357444
- Sponsor's protocol ID
- APHP200406
- Other IDs
- 2020-001571-32
- Acronym
- LILIADE-COVID
- Status last verified
- Apr 2021
- First submitted
- 10 Apr 2020
- Last updated
- 4 Oct 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Kakh M, Doroudchi M, Talepoor A. Induction of Regulatory T Cells After Virus Infection and Vaccination. Immunology. 2025 May 7. doi: 10.1111/imm.13927. Online ahead of print.
PubMed 40329764
Study at a glance
From the registry record, last updated by the sponsor on 4 Oct 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Low Dose of IL-2 In Acute Respiratory DistrEss Syndrome Related to COVID-19
- ClinicalTrials.gov ID
- NCT04357444
- Acronym / sponsor ID
- LILIADE-COVID / APHP200406
- Conditions
- COVID 19
- Keywords
- COVID-19, SARS-CoV2, Acute Respiratory Distress Syndrome, Low dose of IL-2, Immunotherapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Iltoo Pharma
- Study start
- 23 Oct 2020 (actual)
- Primary completion
- 2 Nov 2020 (actual)
- Study completion
- 5 Apr 2021 (actual)
- First posted
- 22 Apr 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose is to demonstrate the efficacy of low-dose interleukin 2 (Ld-IL2) administration in improving clinical course and oxygenation parameters in patients with SARS-CoV2-related ARDS.
Detailed description
About 25% of hospitalized patients with SARS-CoV2 infection presented life-threatening respiratory conditions. Of these, 60% met ARDS criteria leading to death in 25% to 63% of the cases. SARS-CoV2-related ARDS is caused by a massive inflammatory cell infiltration leading to dysregulated cytokine/chemokine responses with lung immunopathological changes. To date, there is no treatment available.
Regulatory T cells (Treg) are a subpopulation of CD4+ T cells playing a crucial role in the control of immune responses, in part by preventing excessive inflammation. Depletion of Treg cells in models of lung infection or after berylium exposure exacerbated lung inflammation. In contrast, a beneficial role for Treg during early ARDS and its resolution has been observed.
Low-dose interleukin 2 (Ld-IL2) is the first therapy driving Treg-specific expansion and activation. Ld-IL2 was successfully tested in a wide range of preclinical models of inflammatory diseases, including beryllium-induced lung inflammation. Moreover, Ld-IL2 has been shown to be safe and free of serious adverse events when administered in patients with various autoimmune diseases. Importantly, in our previous work, we observed only very low concentrations of IL-2 in the blood (0.1 pg/mL [0.0-2.0]) as well as in the BAL supernatant (0.8 pg/mL [0.4-1.3]) collected from patients during the early phase of ARDS, suggesting that additional IL-2 could be beneficial for Treg expansion/activation.
Our objective is therefore to investigate the therapeutic benefit of Ld-IL2 as a Treg inducer for controlling SARS-CoV2-related ARDS.
After admission of patients to the intensive care unit at one of the recruiting centers, the eligibility criteria will be checked by the investigating physician and participation in the study will be proposed to the patient or parent/family member/trusted person. If the patient is unable to consent and there is no parent/family member/trusted person, the patient may be included in the emergency procedure.
After inclusion (J0), the patient will be randomized to one of the 2 treatment arms (low dose IL-2 or placebo).
The experimental treatment will be daily administered to the patient from D1 to D10.
The patient will be monitored daily until D28 during hospitalization.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1: ILT101 | Experimental | Drug: 1: ILT101ILT-101 in Subcutaneous route |
| 2: Placebo Comparator | Placebo comparator | Drug: 2: Placebo ComparatorPlacebo in subcutaneous injections every day during 10 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Male or female, age ≥ 18 years
- Laboratory (RT-PCR) confirmed infection with SARS-CoV2
- Patient is either under invasive or non-invasive mechanical ventilation (including high flow nasal oxygen therapy).
- Diagnosis of ARDS according to the Berlin definition of ARDS
- Onset of ARDS <96 hours
Key exclusion criteria (20 listed)
- Previous history of ARDS in the last month
- Chronic respiratory diseases requiring long-term oxygen therapy and/or long-term respiratory assistance
- History of organ allograft.
- Active cancer
- Liver cirrhosis with basal Child and Pugh of C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 1: ILT101Subcutaneous injections, once-daily administration for 10 consecutive days. | Drug | 1: ILT101 |
| 2: Placebo Comparatorplacebo in Subcutaneous route | Drug | 2: Placebo Comparator |
Primary outcome
The PaO2/FiO2 ratio at D11
Time frame: at Day11
19 secondary outcomes
Changes in Tregs between Baseline and Day 7 (expressed in %)
Time frame: at Day0 and Day7
Number of days alive with oxygen therapy within 28 days
Time frame: at Day28
Maximal oxygen rate within 28 days
Time frame: at Day28
Number of days alive free of invasive or non-invasive ventilation within 28 days
Time frame: At Day28
Number of days alive outside ICU within 28 days
Time frame: at Day28
Number of days alive outside hospital within 28 days
Time frame: at Day28
Time (in days) from randomization to death
Time frame: through study completion at day 28
Mortality rate at D28
Time frame: at Day28
Difference between CRP levels at randomization and at Day 7 (or at the time of discharge if occurs before Day 7)
Time frame: at Day0 and Day7 or at the time of discharge
Use of antibiotics for respiratory (proved or suspected) infection within 28 days
Time frame: at Day28
Number of prone positioning sessions
Time frame: throughout the follow up period at day 28
Changes in Tregs during the different visits between baseline and day 28
Time frame: at Day0, 5, 7, 11, 14 and Day28
Cytokines analysis on plasma samples at Day 0, 7 and 14
Time frame: at Day 0, 7 and 14
Tregs numbers during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.
Time frame: at Day0, 5, 7, 11, 14 and Day28
Tregs percentages during induction period and throughout the follow up period at day 5, 7, 11, 14 and 28 compared to baseline before the first IL-2 injection.
Time frame: at Day0, 5, 7, 11, 14 and Day28
Deep Immunophenotyping of Cellular components in blood samples at Day 0, 7, and 14
Time frame: at Day0, 7 and Day14
T cell repertoire on Treg, after sorting from blood at Day 7 and Day 14 and compared to baseline
Time frame: at Day0, 7 and Day14
T cell repertoire on Teff (CD4 and CD8) after sorting from blood at Day 7 and Day 14 and compared to baseline
Time frame: at Day0, 7 and Day14
Single cells sequencing will be performed in BAL at Day 7 and Day 14 and compared to baseline.
Time frame: at Day0, 7 and Day14
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2021.
- Derived from this study: PubMed 40329764Kakh M, Doroudchi M, Talepoor A. Induction of Regulatory T Cells After Virus Infection and Vaccination. Immunology. 2025 May 7. doi: 10.1111/imm.13927. Online ahead of print.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Michel CONSTANTIN principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 1: ILT101 in people with COVID 19, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Oct 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The PaO2/FiO2 ratio at D11 (time frame: at Day11). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04357444, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Oct 2021.