A Study of Liposomal Trans Crocetin, LEAF-4L6715, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19, Sepsis or Other Causes

Study Overview
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Brief Summary
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This is an open label phase II study of treatment with LEAF-4L6715 in patients who experience severe acute respiratory distress syndrome (ARDS) due to COVID-19, Sepsis or other Causes. The purpose of this study is to evaluate the improvement in PaO2/FiO2 by more than 25% in patients treated with LEAF-4L6715.

Detailed Description
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Patient is treated with LEAF-4L6715, a liposomal transcrocetin. The liposomal formulation allows for a gradual release of the free drug, thereby facilitating less frequent dosing. Pharmacokinetic assessment will be carried out to identify an optimal dose and schedule.

Official Title
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A Study of Liposomal Trans Crocetin, LEAF-4L6715, in Patients With Acute Respiratory Distress Syndrome Due to COVID-19, Sepsis or Other Causes

Conditions
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COVID19, Sepsis or Other Causes, Acute Respiratory Distress Syndrome

Intervention / Treatment
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* Drug: LEAF-4L6715


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent from the patient or patient's legal representative must be obtained prior to any procedures, as the likelihood of patients being able to provide consent is very limited Patients must be ≥ 18 years old Patient must have acute respiratory distress syndrome as defined, with a PaO2/FiO2 ratio of less than 200 mm Hg Patient must be under artificial ventilation support (including patient under OptiflowTM Nasal High Flow device or an equivalent device) Patient must have a life expectancy of at least 24 hours Patients should have normal liver function as defined by ALT, AST and alkaline phosphate less than 3 ULN for the institution Patient must have platelet count above >100,000 cells/mm3, hemoglobin > 8 g/dL and an absolute neutrophil count (ANC) of > 1000 cells/mm3 Patients requiring dialysis due to renal impairment in cohort 3 Exclusion Criteria: Patient is enrolled in any other therapeutic clinical trial with the same endpoints. All observational studies or study with limited invasive methods (Pharmacokinetic studies, monitoring of virus charges studies, biological monitoring studies ….) are allowed Patient is pregnant or breast-feeding Patient has a known hypersensitivity to crocetins, LEAF-4L6715 or any of its excipients Patients with hemoglobinopathy Patients receiving extracorporeal membrane oxygenation (ECMO)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4L6715<br>exploring various doses of LEAF-4L6715 | Drug: LEAF-4L6715<br>* LEAF-4L6715<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients showing an increase of at least 25% of PaO2/FiO2 ratio |  | 24 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of patients with a PaO2/FiO2 ratio above 200 mm Hg |  | 24, 48 and 72 hours | 
| all cause mortality |  | 28 days |