Clinical trial NCT04618042: FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Official title: FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Ards
Covid19
Pneumonia
Keywords: FX06
Pulmonary vascular hyperpermeability
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2020-11-05
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Vascular leakage following endothelial injury, responsible for interstitial and alveolar edema, is a major feature of pathogen induced acute lung injury. As acute respiratory distress syndrome (ARDS) due to pandemic Covid-19 is associated with more than 60% mortality, controlling vascular leakage may be a major target to decrease the mortality associated with the spreading of the disease in France.

FX06, a drug under clinical development containing fibrin-derived peptide beta15-42, is able to stabilize cell-cell interactions, thereby reducing vascular leak and mortality in several animal models, particularly during lipopolysaccharide-induced and dengue hemorrhagic shock . A phase I study was conducted in humans, with no specific adverse event detected with a dose up to 17.5 mg/kg. In a phase II randomized multicentre double-blinded trial in 234 patients suffering from ST+ acute coronary syndrome, FX06 treated patients exhibited a 58% decrease in the early necrotic core zone. Importantly, adverse events were highly comparable between groups, indicating a high safety profile for the drug . Lastly, the drug was used as a salvage therapy in a patient exhibiting a severe ARDS following EBOLA virus infection . Altogether, those data indicate that FX06 is well tolerated in humans and is a potent regulator of vascular leakage.

Our hypothesis here is that FX06 may decrease pulmonary vascular hyperpermeability during ARDS following SARS-CoV-2 infection, thereby improving gas exchanges and the outcome of infected patients.


Eligibility criteria: Inclusion Criteria:

1. Age ≥ 18 years
2. SARS-CoV-2 induced pneumonia confirmed by a positive PCR test in nasopharyngeal swab or respiratory tract secretions and ≤ 85 years
3. Acute respiratory distress syndrome (ARDS) according to Berlin criteria (bilateral pulmonary infiltrates on frontal chest x-ray, PaO2/FiO2 ratio ≤300 mmHg, objective assessment excluding hydrostatic pulmonary edema)
4. Need for endotracheal intubation and mechanical ventilation
5. Informed consent by patient or legal representative. According to the specifications of emergency consent, randomization without the close relative or surrogate consent could be performed.
6. Affiliated to a social security system
7. Highly effective method of contraception and negative highly sensitive pregnancy test, for women of childbearing potential

Exclusion Criteria:

1. Mechanically ventilation for more than 4 days
2. Patient receiving drugs interfering with inflammation: Non-steroidal anti-inflammatory drugs, immunoglobulins.
3. Patients receiving chemotherapy, radiotherapy or immunotherapy for malignancy
4. Participation in another interventional clinical trial
5. Pregnant or lactating women
6. Patient moribund on the day of randomization, defined by a SAPS-II score\>90
7. Contra-indication for vascular access implantation for transpulmonary thermodilution monitoring
8. Severe or terminal renal insufficiency (creatinine clearance \<30 ml/min)
9. Severe hepatic insufficiency (hepatic SOFA score\>2)
10. Severe cardiac insufficiency, with left ventricular ejection fraction\<30%
11. Any history of severe allergic drug reaction (anaphylactic shock or allergic angioedema)
12. Persons deprived of their liberty by a judicial or administrative decision (guardianship or tutelage measure)

Primary outcomes:
measure: Change in extravascular lung water index (EVLWi)
timeFrame: Between Day 1 and Day 7
Secondary outcomes:
measure: Evolution of daily extravascular lung water index (EVLWi)
timeFrame: Between Day 1 and Day 7
measure: Evolution of daily cardiac index
timeFrame: Between Day 1 and Day 7
measure: Evolution of global end-diastolic volume index
timeFrame: Between Day 1 and Day 7
measure: Evolution of pulmonary vascular permeability index
timeFrame: Between Day 1 and Day 7
measure: Overall survival
timeFrame: Day 30
measure: Mortality rate in ICU and in hospital
timeFrame: Through study completion an average of 2 months
measure: Rate of withdraw or withhold life-sustaining treatments decision
timeFrame: Day 30
measure: Daily weight
timeFrame: Between Day 1 and Day 7
measure: Daily fluid balance
timeFrame: Between Day 1 and Day 7
measure: Evolution of albuminemia
timeFrame: Between Day 1 and Day 7
measure: Duration of mechanical ventilation
timeFrame: Day 30
measure: Proportion of participants alive and off invasive mechanical ventilation
timeFrame: Day 30
measure: Evolution of Murray ARDS severity score
timeFrame: Day 1 to day 15
measure: Evolution of radiological Weinberg score
timeFrame: Day 1 to Day 30
measure: Evolution of pulmonary Sequential Organ Failure Assessment) score.
timeFrame: Day 1 to day 15
measure: Rate of rescue therapy with Veino-veinous V-ECMO
timeFrame: Through study completion an average of 2 months
measure: Evolution of SOFA (Sequential Organ Failure Assessment) score
timeFrame: Day 15
measure: Organ failure free days
timeFrame: Day 15
measure: Renal replacement therapy free days
timeFrame: Day 30
measure: Duration of renal replacement therapy free days
timeFrame: Day 30
measure: Nature and frequency of adverse events
timeFrame: Through study completion an average of 2 months
measure: Evolution of FX06 concentration
timeFrame: Day 1
measure: Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure
timeFrame: Day 7
Other outcomes:
Locations:
city: Angers
country: France
facility: Service de Médecine Intensive Réanimation - CHU Angers
city: Chambourcy
country: France
facility: Service de Médecine Intensive Réanimation - CHI de Poissy
city: Paris
country: France
facility: Hôpital Pitié Salpêtrière
Study officials:
References: