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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04618042
Recruitment Status : Recruiting
First Posted : November 5, 2020
Last Update Posted : January 11, 2021
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris

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
Ards Covid19 Pneumonia Drug: FX06 Drug: Placebo of FX06 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: FX06 to Rescue Acute Respiratory Distress Syndrome During Covid-19 Pneumonia
Actual Study Start Date : November 13, 2020
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : July 2021


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




Primary Outcome Measures :
  1. Change in extravascular lung water index (EVLWi) [ Time Frame: 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 :
  1. Evolution of daily extravascular lung water index (EVLWi) [ Time Frame: Between Day 1 and Day 7 ]
    measured by transpulmonary thermodilution during 7 days

  2. Evolution of daily cardiac index [ Time Frame: Between Day 1 and Day 7 ]
    measured by transpulmonary thermodilution during 7 days

  3. Evolution of global end-diastolic volume index [ Time Frame: Between Day 1 and Day 7 ]
    measured by transpulmonary thermodilution during 7 days

  4. Evolution of pulmonary vascular permeability index [ Time Frame: Between Day 1 and Day 7 ]
    measured by transpulmonary thermodilution during 7 days

  5. Overall survival [ Time Frame: Day 30 ]
  6. Mortality rate in ICU and in hospital [ Time Frame: Through study completion an average of 2 months ]
  7. Rate of withdraw or withhold life-sustaining treatments decision [ Time Frame: Day 30 ]
  8. Daily weight [ Time Frame: Between Day 1 and Day 7 ]
  9. Daily fluid balance [ Time Frame: Between Day 1 and Day 7 ]
  10. Evolution of albuminemia [ Time Frame: Between Day 1 and Day 7 ]
    Evolution of blood biological criteria (g/L)

  11. Duration of mechanical ventilation [ Time Frame: Day 30 ]
  12. Proportion of participants alive and off invasive mechanical ventilation [ Time Frame: Day 30 ]
  13. Evolution of Murray ARDS severity score [ Time Frame: Day 1 to day 15 ]
  14. Evolution of radiological Weinberg score [ Time Frame: Day 1 to Day 30 ]
    Scale from 0 to 12 better with higher score indicating more severe radiological pulmonary severity

  15. Evolution of pulmonary Sequential Organ Failure Assessment) score. [ Time Frame: Day 1 to day 15 ]
    Scale from 0 to 4 betterwith higher score indicating more severe pulmonary disease

  16. Rate of rescue therapy with Veino-veinous V-ECMO [ Time Frame: Through study completion an average of 2 months ]
  17. Evolution of SOFA (Sequential Organ Failure Assessment) score [ Time Frame: Day 15 ]
    Scale from 0 to 24, lower is better.

  18. Organ failure free days [ Time Frame: Day 15 ]
    one or more SOFA sub-score >=3

  19. Renal replacement therapy free days [ Time Frame: Day 30 ]
  20. Duration of renal replacement therapy free days [ Time Frame: Day 30 ]
  21. Nature and frequency of adverse events [ Time Frame: Through study completion an average of 2 months ]
  22. Evolution of FX06 concentration [ Time Frame: Day 1 ]
    measured at day 1 at time 0 (before FX06 application) and after 5, 15, 30, 60 min

  23. Immunogenicity (antibody against FX06) induced by the drug, performed by ELISA according to manufacturer's procedure [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04618042


Contacts
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Contact: Nicolas BRECHOT, MD +33142163835 nicolas.brechot@aphp.fr
Contact: David HAJAGE, MD +33142160553 david.hajage@aphp.fr

Locations
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France
Service de Médecine Intensive Réanimation - CHU Angers Recruiting
Angers, France, 49933
Contact: Pierre ASFAR, MD       piAsfar@chu-angers.fr   
Service de Médecine Intensive Réanimation - CHI de Poissy Recruiting
Chambourcy, France, 78240
Contact: Yan HAYON, MD       jan.hayon@ght-yvelinesnord.fr   
Hôpital Pitié Salpêtrière Recruiting
Paris, France, 75013
Contact: BRECHOT Nicolas, MD       nicolas.brechot@aphp.fr   
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04618042    
Other Study ID Numbers: APHP200495
2020-002056-20 ( EudraCT Number )
First Posted: November 5, 2020    Key Record Dates
Last Update Posted: January 11, 2021
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
FX06
Pulmonary vascular hyperpermeability
Additional relevant MeSH terms:
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Pneumonia
Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Lung Diseases
Respiratory Tract Diseases
Respiratory Tract Infections
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury