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

NCT ID: NCT04618042

Last Updated: 2021-06-22

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-11-13
• Study Completion Date: 2021-06-13

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

FX06

Group Type: EXPERIMENTAL

FX06

Intervention Type: DRUG

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

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo of FX06

Intervention Type: DRUG

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

Interventions

FX06

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

Intervention Type: DRUG

Placebo of FX06

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

Intervention Type: DRUG

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Service de Médecine Intensive Réanimation - CHU Angers

Angers, , France

Service de Médecine Intensive Réanimation - CHI de Poissy

Chambourcy, , France

Hôpital Pitié Salpêtrière

Paris, , France

Countries

France

References

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.

Reference Type: DERIVED

PMID: 37641136 (View on PubMed)

Other Identifiers

2020-002056-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

APHP200495

Identifier Type: -

Identifier Source: org_study_id