A Phase 3 interventional study of LEAF-4L6715 and Supportive Care in Acute Respiratory Distress Syndrome, sponsored by LEAF4Life, Inc.. Not yet recruiting at 1 site in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-10-15.
Sponsored by LEAF4Life, Inc. · Phase 3, Interventional, and Treatment
Acute Respiratory Distress Syndrome (ARDS) is a serious condition where people in hospital care suddenly have trouble breathing because of infection, pneumonia, COVID-19 or other disease. People with ARDS may have to be put in an intensive care unit (ICU) and on a ventilator to help them breathe. This trial is to try to find out if injecting a product called LEAF-4L6715 makes the treatment better or worse than what is normally given. LEAF-4L6715 is a product that contains tiny bubbles to slowly release a substance named transcrocetin which scientific studies show may increase oxygen flow and reduce inflamed cells and protect tissues of the body.
Study Design: Prospective, international, multicenter, open label, randomized, controlled, two-arm study.
Study Objective(s): The primary objective of the study is to determine if the addition of LEAF-4L6715 to Standard of Care (SOC) treatment may improve clinical outcomes at 30-days, including survival and duration of mechanical ventilation (MV), in patients with Acute Respiratory Distress Syndrome (ARDS) compared to SOC treatment alone.
The secondary objectives are to compare other relevant respiratory and clinical outcomes and safety between the two groups during Intensive Care Unit (ICU) stay, hospitalization, and follow-up, including percentage of patients alive at 60 days and 90 days from randomization.
Rationale: The scientific and clinical observations to date strongly suggest that transcrocetin (TC) may be a good candidate for the treatment of hypoxic conditions such as moderate to severe ARDS. Indeed, TC plays a major role in enhancing oxygen diffusion, but also in reducing inflammation and protecting tissues. However, TC's poor stability and solubility and its short in vivo half-life of \~30mins resulted in transient oxygenation effect. LEAF-4L6715 was designed to be a stable TC formulation with a 6-fold increase in half-life and a 12-fold increase in drug exposure compared to free TC, resulting in a more sustained oxygenation compared with free TC.
Developed as a liposomal formulation of TC, LEAF-4L6715 allows for a gradual release of the free drug and was evaluated at multiple levels (1) in vitro in Human Umbilical Vein Endothelial Cells (HUVECs); (2) in vivo in healthy mice (n=40) as well as in a mouse model of sepsis (n=10) and (3) in a clinical trial evaluating Pharmacokinetics (PK) and safety. A phase 1/2 trial which included 37 patients defined the optimal dose regimen and intravenous infusion timing and confirmed the safety of LEAF-4L6715. It also showed promising trends in therapeutic efficacy.
1,619 studies on the registry are indexed under Respiratory Distress Syndrome; 319 are open to participants now.
This study's planned enrollment of 310 is above the median of 60 across 973 interventional studies indexed under Respiratory Distress Syndrome.
Browse Respiratory Distress Syndrome studies →This is the only study on the registry with LEAF4Life, Inc. as lead sponsor.
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Patients will be included if all of the following criteria are met:
Exclusion Criteria:
LEAF-4L6715 administered Intravenously 200 mg every 12h for 2 days, then 200 mg Intravenously every 24 hours for 8 days (total 10 days dosing) Supportive care, as considered necessary by the treating physician/Principal Investigator (PI), including mechanical ventilation, in line with therapeutic guidelines for ARDS and Multiorgan Failure
Drug: LEAF-4L6715 · Drug: Supportive Care
Description: Supportive care, as considered necessary by the treating physician/Principal Investigator (PI), including mechanical ventilation, in line with therapeutic guidelines for ARDS and Multiorgan Failure
Drug: Supportive Care
LEAF-4L6715: Administration at a dose of 200mg , for up to 10 days every 12 hours for the first 2 days, followed by once-a-day dosing for the next 8 days (days 3 through 10).
Also known as: Liposomal transcrocetin
Supportive care, as considered necessary by the treating physician/Principal Investigator (PI), including mechanical ventilation, in line with therapeutic guidelines for ARDS and Multiorgan Failure
Days free from invasive mechanical ventilation
From Randomization to Day 30
Time frame: 30 Days
30 Day All-Cause Mortality
Survival at Day 30
Time frame: 30 days
Mean total of Sequential Organ Failure Assessment (SOFA) score
Mean total of Sequential Organ Failure Assessment (SOFA) score and sub-scores during the treatment period.
Time frame: 30 days
Need for rescue procedures
Need for rescue procedures such as prone positioning, inhaled nitric oxide (NO), recruitment maneuvers, extracorporeal membrane oxygenation (ECMO).
Time frame: 30 days
Ventilator-associated pneumonia treated with antibiotics between randomization and 30 days.
Proportion of patients with ventilator-associated pneumonia treated with antibiotics between randomization and 30 days.
Time frame: 30 days
Number of days alive without organ failure at 30 days and 60 days
Number of days alive without organ failure at 30 days and 60 days, using the SOFA score and its components
Time frame: 60 days
Mean reduction in the WHO 9-point Ordinal Scale score
Mean reduction in the WHO 9-point Ordinal Scale score from start of treatment to 30 days
Time frame: 30 days
Length of ICU stay
Number of days patient was in Intensive Care Unit
Time frame: 60 days
Length of hospital stay
Number of days patient stayed in hospital
Time frame: 60 Days
Incidence of serious adverse events (SAEs), AEs, and treatment-emergent adverse events
Incidence of serious adverse events (SAEs), AEs, and treatment-emergent adverse events by maximum Common Terminology Criteria for Adverse Events (CTCAE) grade and/or change in baseline laboratory values
Time frame: 90 Days or event resolution/stabilization
Change in Quality of Life (QOL) by Health economics and outcomes research assessments
Change in Quality of Life (QOL) by Health economics and outcomes research assessments: to compare patient QOL using European QOL Five Dimension (EQ-5D-5L)
Time frame: 90 days
Survival at 30, 60 and 90 days
Number of patients alive at 30, 60 and 90 days from randomization.
Time frame: 90 days
PaO2/FiO2 ratio
Number of patients with an improvement of 25% in PaO2/FiO2 ratio at 72 hours post-treatment initiation and over time until acute treatment discontinuation.
Time frame: 30 days
Time to successful extubation
Time in hours to successful extubation without re-intubation or death within the next 48 Hours
Time frame: 30 days
Total duration of mechanical ventilation
Total duration of MV in days and the number of days, between randomization and 30 days, alive without MV.
Time frame: 30 days
Pharmacokinetics (PK) assessments
12\. Maximum plasma concentration (Cmax) , units μg/ml
Time frame: Day 1, Day 3, Day 14 and Day 30
Pharmacokinetic (PK) Assessments
Area under the curve (AUC) units h\*μg/ml
Time frame: Day 1, Day 3, Day 14 and Day 30
Plan to share: No
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