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

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.

Study Overview

• Status: Completed
• Conditions: Acute Respiratory Distress Syndrome; COVID19, Sepsis or Other Causes
• Intervention / Treatment: Drug: LEAF-4L6715

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• France
  • Strasbourg, France, 67033
    • Institut de cancerologie Strasbourg Europe
  • Strasbourg, France, 67000
    • Hôpitaux Universitaires de Strasbourg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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
2. Patients must be ≥ 18 years old
3. Patient must have acute respiratory distress syndrome as defined, with a PaO2/FiO2 ratio of less than 200 mm Hg
4. Patient must be under artificial ventilation support (including patient under OptiflowTM Nasal High Flow device or an equivalent device)
5. Patient must have a life expectancy of at least 24 hours
6. Patients should have normal liver function as defined by ALT, AST and alkaline phosphate less than 3 ULN for the institution
7. Patient must have platelet count above >100,000 cells/mm3, hemoglobin > 8 g/dL and an absolute neutrophil count (ANC) of > 1000 cells/mm3
8. Patients requiring dialysis due to renal impairment in cohort 3

Exclusion Criteria:

1. 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
2. Patient is pregnant or breast-feeding
3. Patient has a known hypersensitivity to crocetins, LEAF-4L6715 or any of its excipients
4. Patients with hemoglobinopathy
5. Patients receiving extracorporeal membrane oxygenation (ECMO)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 4L6715; exploring various doses of LEAF-4L6715	Drug: LEAF-4L6715; LEAF-4L6715

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Institut de cancérologie Strasbourg Europe
• Collaborators: LEAF4Life, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): April 14, 2020
• Primary Completion (Actual): August 24, 2021
• Study Completion (Actual): August 24, 2021

Study Registration Dates

• First Submitted: May 5, 2020
• First Submitted That Met QC Criteria: May 6, 2020
• First Posted (Actual): May 7, 2020

Study Record Updates

• Last Update Posted (Actual): December 16, 2021
• Last Update Submitted That Met QC Criteria: December 15, 2021
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Inflammation; Disease; Infant, Newborn, Diseases; Lung Injury; Infant, Premature, Diseases; COVID-19; Sepsis; Toxemia; Syndrome; Respiratory Distress Syndrome; Respiratory Distress Syndrome, Newborn; Acute Lung Injury
• Other Study ID Numbers: 2020-003; 2020-001393-30 (EudraCT Number); 2020-A00900-39 (Other Identifier: IDRCB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes