FX-COVID: FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: FX06
|
Drug: FX06
FX06 i.v.: 400 mg per day (divided in two injections) during 5 days
|
| Placebo Comparator: Placebo
|
Drug: Placebo of FX06
Placebo i.v.: 400 mg per day (divided in two injections) during 5 days
|
Outcome Measures
Primary Outcome Measures
- Change in extravascular lung water index (EVLWi) [Between Day 1 and Day 7]
Assessed by transpulmonary thermodilution Transpulmonary thermodilution systems, part of the standard management in ICU, allow a direct evaluation of vascular hyperpermeability in the lungs using thermodilution technique. EVLWi is a reliable parameter, independently associated with mortality during ARDS
Secondary Outcome Measures
- Evolution of daily extravascular lung water index (EVLWi) [Between Day 1 and Day 7]
measured by transpulmonary thermodilution during 7 days
- Evolution of daily cardiac index [Between Day 1 and Day 7]
measured by transpulmonary thermodilution during 7 days
- Evolution of global end-diastolic volume index [Between Day 1 and Day 7]
measured by transpulmonary thermodilution during 7 days
- Evolution of pulmonary vascular permeability index [Between Day 1 and Day 7]
measured by transpulmonary thermodilution during 7 days
- Overall survival [Day 30]
- Mortality rate in ICU and in hospital [Through study completion an average of 2 months]
- Rate of withdraw or withhold life-sustaining treatments decision [Day 30]
- Daily weight [Between Day 1 and Day 7]
- Daily fluid balance [Between Day 1 and Day 7]
- Evolution of albuminemia [Between Day 1 and Day 7]
Evolution of blood biological criteria (g/L)
- Duration of mechanical ventilation [Day 30]
- Proportion of participants alive and off invasive mechanical ventilation [Day 30]
- Evolution of Murray ARDS severity score [Day 1 to day 15]
- Evolution of radiological Weinberg score [Day 1 to Day 30]
Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity
- Evolution of pulmonary Sequential Organ Failure Assessment) score. [Day 1 to day 15]
Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease
- Rate of rescue therapy with Veino-veinous V-ECMO [Through study completion an average of 2 months]
- Evolution of SOFA (Sequential Organ Failure Assessment) score [Day 15]
Scale from 0 to 24, lower is better.
- Organ failure free days [Day 15]
one or more SOFA sub-score >=3
- Renal replacement therapy free days [Day 30]
- Duration of renal replacement therapy free days [Day 30]
- Nature and frequency of adverse events [Through study completion an average of 2 months]
- Evolution of FX06 concentration [Day 1]
measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min
- Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure [Day 7]
A test for immunogenicity will be performed on a serum sample at day 7 (2 days after the end of treatment administration) to detect any antibody against FX06. The assay will consist in a three-fold procedure, as recommended by the manufacturer. An initial screening assay will qualitatively measure antibodies to FX06. Samples deemed positive will be subject to a confirmatory assay, which will determine the specificity of the detected antibody against FX06. The third tier of the assay will consist in titre analysis to semi-quantitatively assess the antibody response.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age ≥ 18 years
-
SARS-CoV-2 induced pneumonia confirmed by a positive PCR test in nasopharyngeal swab or respiratory tract secretions and ≤ 85 years
-
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)
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Need for endotracheal intubation and mechanical ventilation
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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.
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Affiliated to a social security system
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Highly effective method of contraception and negative highly sensitive pregnancy test, for women of childbearing potential
Exclusion Criteria:
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Mechanically ventilation for more than 4 days
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Patient receiving drugs interfering with inflammation: Non-steroidal anti-inflammatory drugs, immunoglobulins.
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Patients receiving chemotherapy, radiotherapy or immunotherapy for malignancy
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Participation in another interventional clinical trial
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Pregnant or lactating women
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Patient moribund on the day of randomization, defined by a SAPS-II score>90
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Contra-indication for vascular access implantation for transpulmonary thermodilution monitoring
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Severe or terminal renal insufficiency (creatinine clearance <30 ml/min)
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Severe hepatic insufficiency (hepatic SOFA score>2)
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Severe cardiac insufficiency, with left ventricular ejection fraction<30%
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Any history of severe allergic drug reaction (anaphylactic shock or allergic angioedema)
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Persons deprived of their liberty by a judicial or administrative decision (guardianship or tutelage measure)
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Service de Médecine Intensive Réanimation - CHU Angers | Angers | France | 49933 | |
| 2 | Service de Médecine Intensive Réanimation - CHI de Poissy | Chambourcy | France | 78240 | |
| 3 | Hôpital Pitié Salpêtrière | Paris | France | 75013 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP200495
- 2020-002056-20