Low Dose of IL-2 In Acute Respiratory DistrEss Syndrome Related to COVID-19

NCT ID: NCT04357444

Last Updated: 2021-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-23
• Study Completion Date: 2021-04-05

Brief 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.

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

Study Design

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

Study Groups

1: ILT101

ILT-101 in Subcutaneous route

Group Type: EXPERIMENTAL

1: ILT101

Intervention Type: DRUG

Subcutaneous injections, once-daily administration for 10 consecutive days.

2: Placebo Comparator

Placebo in subcutaneous injections every day during 10 days

Group Type: PLACEBO_COMPARATOR

2: Placebo Comparator

Intervention Type: DRUG

placebo in Subcutaneous route

Interventions

1: ILT101

Subcutaneous injections, once-daily administration for 10 consecutive days.

Intervention Type: DRUG

2: Placebo Comparator

placebo in Subcutaneous route

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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
• 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).

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

Sponsors

Iltoo Pharma

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Michel CONSTANTIN

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Service Anesthésie Réanimation - Groupe Hospitalier Pitié-Salpêtrière

Paris, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 40329764 (View on PubMed)

Other Identifiers

2020-001571-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200406

Identifier Type: -

Identifier Source: org_study_id