FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia

NCT04618042 | Completed Phase 2 DMC

• 2 other identifiers: APHP2004952020-002056-20
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 3

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.

Conditions

Ards; Covid19; Pneumonia

Keywords

FX06; Pulmonary vascular hyperpermeability

Outcome Measures

Primary Outcomes (1)

• Change in extravascular lung water index (EVLWi)

  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

  Between Day 1 and Day 7

Secondary Outcomes (23)

• Evolution of daily extravascular lung water index (EVLWi)

  Between Day 1 and Day 7

• Evolution of daily cardiac index

  Between Day 1 and Day 7

• Evolution of global end-diastolic volume index

  Between Day 1 and Day 7

• Evolution of pulmonary vascular permeability index

  Between Day 1 and Day 7

• Overall survival

  Day 30

Study Arms (2)

FX06

EXPERIMENTAL

Drug: FX06

Placebo

PLACEBO COMPARATOR

Drug: Placebo of FX06

Interventions

FX06 DRUG

FX06 i.v.: 400 mg per day (divided in two injections) during 5 days

FX06

Placebo of FX06 DRUG

Placebo i.v.: 400 mg per day (divided in two injections) during 5 days

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)
• Need for endotracheal intubation and mechanical ventilation
• 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.
• Affiliated to a social security system
• Highly effective method of contraception and negative highly sensitive pregnancy test, for women of childbearing potential

You may not qualify if:

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

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (3)

Service de Médecine Intensive Réanimation - CHU Angers

Angers, 49933, France

Location

Service de Médecine Intensive Réanimation - CHI de Poissy

Chambourcy, 78240, France

Location

Hôpital Pitié Salpêtrière

Paris, 75013, France

Location

Related Publications (1)

• Guerin E, Belin L, Franchineau G, Le Guennec L, Hajage D, Diallo MH, Frapard T, Le Fevre L, Luyt CE, Combes A, Germain S, Hayon J, Asfar P, Brechot N. FX06 to rescue SARS-CoV-2-induced acute respiratory distress syndrome: a randomized clinical trial. Crit Care. 2023 Aug 29;27(1):331. doi: 10.1186/s13054-023-04616-1.

  PMID: 37641136 DERIVED

MeSH Terms

Conditions

Acute Lung Injury; COVID-19; Pneumonia

Condition Hierarchy (Ancestors)

Lung Injury; Lung Diseases; Respiratory Tract Diseases; Pneumonia, Viral; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 23, 2020
• First Posted: November 5, 2020
• Study Start: November 13, 2020
• Primary Completion: May 14, 2021
• Study Completion: June 13, 2021
• Last Updated: June 22, 2021

Record last verified: 2021-06

Locations

FR (3)