FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia (FX-COVID)

Assistance Publique - Hôpitaux de Paris

Status and phase: Completed; Phase 2

Conditions: Covid19; Ards; Pneumonia

Treatments: Drug: Placebo of FX06; Drug: FX06

Study type: Interventional

Funder types: Other

Identifiers

NCT04618042

APHP200495

2020-002056-20 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 50 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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50 participants in 2 patient groups, including a placebo group

FX06

Experimental group

Treatment:

Drug: FX06

Placebo

Placebo Comparator group

Treatment:

Drug: Placebo of FX06