Acute Respiratory Distress SyndromePhase 3NCT06640777
Efficacy and Safety of LEAF-4L6715 for Acute Respiratory Distress Syndrome
A Phase 3 study testing LEAF-4L6715 and Supportive Care in people with Acute Respiratory Distress Syndrome, run by LEAF4Life, Inc. at 1 site in France.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Respiratory Distress Syndrome
- What is being tested?
- LEAF-4L6715 and Supportive Care
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 310 participants
- Where
- 1 siteFrance
- Study dates
- 1 Nov 2024to 9 Nov 2027
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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
- Patients will be included if all of the following criteria are met:
- Patients ≥18 years old
- Signed and dated informed consent from patient's trusted person before any study related procedures, pursuing patient signature as soon as patient health condition allows
- ARDS with a documented Positive End-Expiratory Pressure (PEEP) ≥5 and PaO2/FiO2 ratio of ≤200 mm Hg for a minimum of 24 hours prior to randomization
- Patient with an endotracheal tube or tracheostomy tube and receiving MV support
- Life expectancy of at least 24 hours from randomization
Show all 9Show fewer
- Alanine transaminase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) < 3 x upper limit of normal at the time of randomization
- Male or non-pregnant female patient
- Affiliated to a social security system (for France)
Who cannot join
- Enrolled in any other therapeutic clinical trial or receiving an experimental drug (only observational studies allowed)
- Hypersensitivity to crocetins, LEAF 4L6715 or any of its excipients.
- Receiving extracorporeal membrane oxygenation (ECMO) treatment
- On MV for more than 7 days
- Chronic Obstructive Pulmonary Disease (COPD) or other respiratory insufficiency with home ventilation or oxygen therapy
- Severe underlying pre-existing condition with expected 6 months mortality >50% or survival <50%
Show all 9Show fewer
- Patient moribund, decision to limit therapeutic interventions
- Unwilling or unable to comply with study procedures
- Under guardianship, curatorship or safeguard of justice (for France)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Solenne Paiva, Ph.D. contact
France1 site
Sorbonne University
Paris, Paris
Alain Combes, +33 (0)1 42 16 38 18, alain.combes@aphp.fr
Alain Combes, MD
About this study
Official title: Multicenter, Randomized, Open-Label Phase 3 Study to Investigate Efficacy and Safety of Liposomal Transcrocetin(LEAF-4L6715) Plus Standard of Care Vs Standard of Care Alone for Treatment of Patients with Acute Respiratory Distress Syndrome
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.
Read the detailed description
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.
- Conditions
- Acute Respiratory Distress Syndrome
- Being tested
- LEAF-4L6715, Supportive Care
- Keywords
- ARDS
- Medical subject headings
- Respiratory Distress Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LEAF-4L6715Drug
Also called Liposomal transcrocetin
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).
Supportive CareDrug
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
| Study group | Role | What they receive |
|---|---|---|
| LEAF-4L6715 (Liposomal Transcrocetin) + Supportive Care | Experimental | 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 Receives: Drug: LEAF-4L6715; Drug: Supportive Care |
| Supportive Care | Active comparator | 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 Receives: Drug: Supportive Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Days free from invasive mechanical ventilation
From Randomization to Day 30
Measured: 30 Days
30 Day All-Cause Mortality
Survival at Day 30
Measured: 30 days
Secondary outcomes (15)
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.
Measured: 30 days
Need for rescue procedures
Need for rescue procedures such as prone positioning, inhaled nitric oxide (NO), recruitment maneuvers, extracorporeal membrane oxygenation (ECMO).
Measured: 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.
Measured: 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
Measured: 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
Measured: 30 days
Length of ICU stay
Number of days patient was in Intensive Care Unit
Measured: 60 days
Length of hospital stay
Number of days patient stayed in hospital
Measured: 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
Measured: 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)
Measured: 90 days
Survival at 30, 60 and 90 days
Number of patients alive at 30, 60 and 90 days from randomization.
Measured: 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.
Measured: 30 days
Time to successful extubation
Time in hours to successful extubation without re-intubation or death within the next 48 Hours
Measured: 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.
Measured: 30 days
Pharmacokinetics (PK) assessments
- Maximum plasma concentration (Cmax) , units μg/ml
Measured: Day 1, Day 3, Day 14 and Day 30
Pharmacokinetic (PK) Assessments
Area under the curve (AUC) units h*μg/ml
Measured: Day 1, Day 3, Day 14 and Day 30
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Oct 2024
- Study start1 Nov 2024 (estimated)
- Primary completion9 Nov 2026 (estimated)
- Study completion9 Nov 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Respiratory Distress SyndromeStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, international, multicenter, open label, randomized, controlled, two-arm study.
- Masking
- None (open label)
- Enrolment
- 310 participants (estimated)
Sponsor and investigators
- Lead sponsor
- LEAF4Life, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- European Cardiovascular Research Center
- Responsible party
- Sponsor
- Investigators
- Alain Combes, MD, Principal investigator, Hôpital de la Pitié SalpêtrièreMarie Claude Morice, Ph.D., Study director, CERC - CARDIOVASCULAR EUROPEAN RESEARCH CENTERClet Niyikiza, Ph.D., Study chair, LEAF4Life, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06640777
- Sponsor's protocol ID
- LEAF-4L6715-03-01-01
- Status last verified
- Aug 2024
- First submitted
- 9 Aug 2024
- Last updated
- 15 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 15 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multicenter, Randomized, Open-Label Phase 3 Study to Investigate Efficacy and Safety of Liposomal Transcrocetin(LEAF-4L6715) Plus Standard of Care Vs Standard of Care Alone for Treatment of Patients with Acute Respiratory Distress Syndrome
- ClinicalTrials.gov ID
- NCT06640777
- Acronym / sponsor ID
- LEAF-4L6715-03-01-01
- Conditions
- Acute Respiratory Distress Syndrome
- Keywords
- ARDS
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 310 participants (estimated)
- Lead sponsor
- LEAF4Life, Inc.Industry (pharma, biotech, devices)
- Collaborators
- European Cardiovascular Research Center
- Study start
- 1 Nov 2024 (estimated)
- Primary completion
- 9 Nov 2026 (estimated)
- Study completion
- 9 Nov 2027 (estimated)
- First posted
- 15 Oct 2024 (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.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Prospective, international, multicenter, open label, randomized, controlled, two-arm study.
| Arm | Type | Receives |
|---|---|---|
| LEAF-4L6715 (Liposomal Transcrocetin) + Supportive Care | Experimental | Drug: LEAF-4L6715, Drug: Supportive CareLEAF-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 |
| Supportive Care | Active comparator | Drug: Supportive CareDescription: 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Patients will be included if all of the following criteria are met:
Key exclusion criteria (9 listed)
- Enrolled in any other therapeutic clinical trial or receiving an experimental drug (only observational studies allowed)
- Hypersensitivity to crocetins, LEAF 4L6715 or any of its excipients.
- Receiving extracorporeal membrane oxygenation (ECMO) treatment
- On MV for more than 7 days
- Chronic Obstructive Pulmonary Disease (COPD) or other respiratory insufficiency with home ventilation or oxygen therapy
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 |
|---|---|---|
| LEAF-4L6715Also: Liposomal transcrocetinLEAF-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). | Drug | LEAF-4L6715 (Liposomal Transcrocetin) + Supportive Care |
| Supportive CareSupportive 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 (Liposomal Transcrocetin) + Supportive Care, Supportive Care |
Primary outcome
Days free from invasive mechanical ventilation
Time frame: 30 Days
From Randomization to Day 30
30 Day All-Cause Mortality
Time frame: 30 days
Survival at Day 30
15 secondary outcomes
Mean total of Sequential Organ Failure Assessment (SOFA) score
Time frame: 30 days
Need for rescue procedures
Time frame: 30 days
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
Time frame: 60 days
Mean reduction in the WHO 9-point Ordinal Scale score
Time frame: 30 days
Length of ICU stay
Time frame: 60 days
Length of hospital stay
Time frame: 60 Days
Incidence of serious adverse events (SAEs), AEs, and treatment-emergent adverse events
Time frame: 90 Days or event resolution/stabilization
Change in Quality of Life (QOL) by Health economics and outcomes research assessments
Time frame: 90 days
Survival at 30, 60 and 90 days
Time frame: 90 days
PaO2/FiO2 ratio
Time frame: 30 days
Time to successful extubation
Time frame: 30 days
Total duration of mechanical ventilation
Time frame: 30 days
Pharmacokinetics (PK) assessments
Time frame: Day 1, Day 3, Day 14 and Day 30
Pharmacokinetic (PK) Assessments
Time frame: Day 1, Day 3, Day 14 and Day 30
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Oct 2024.
- Individual participant dataSharing planned: No
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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.
Solenne Paiva, Ph.D. contact
Alain Combes, MD principal investigator
Hôpital de la Pitié Salpêtrière
Marie Claude Morice, Ph.D. study director
CERC - CARDIOVASCULAR EUROPEAN RESEARCH CENTER
Clet Niyikiza, Ph.D. study chair
LEAF4Life, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing LEAF-4L6715 and Supportive Care in people with Acute Respiratory Distress Syndrome, run by LEAF4Life, Inc. 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 9 inclusion and 9 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: opening soon, as of the sponsor's last update on 15 Oct 2024. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Ute Windhovel, Ph.D. ((609) 2168944, uwindhovel@cerc-europe.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Days free from invasive mechanical ventilation (time frame: 30 Days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Oct 2024.