Respiratory Distress Syndrome Related to SARS-Cov-2
Conditions
Interventions
Product Name: glenzocimab
Product Code: ACT017
Pharmaceutical Form: Solution for infusion
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous
Sponsors
ACTICOR BIOTECH
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female hospitalized patients = 18 years (i.e., at least 18 years old at the time of randomization) and 2.5 µg/L c. and/or signs of micro-angiopathy on a vascular enhanced chest CT-scan 7. With one or more of the following biological markers of progression: • CRP =10 mg/L, • LDH > 250 U/L, • IL6 > 8 pg/mL, • Lymphocyte count 88 pg/mL, • Pro-calcitonin > 0.5 ng/mL, • Ferritin > 400 µg/L 8. Effective birth control that should have been in place for at least 2 months in non-menopausal women and 4 months for men after IMP administration. Birth control methods considered to be highly effective include: • combined (estrogen-progestogen) hormonal contraception associated with the inhibition of ovulation: oral, intravaginal, transdermal, • progesterone-only hormonal contraception associated with the inhibition of ovulation: oral, injectable, implantable, • intrauterine device, • intrauterine hormone-releasing system, • bilateral tubal occlusion, • vasectomized partner. 9. Women of child-bearing potential must have negative results of a urinary or plasma pregnancy test (serum HCG). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 30 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 30
Exclusion criteria
Exclusion criteria: 1. Patients requiring immediate admission to the ICU, 2. Patients requiring invasive mechanical ventilation, 3. Obvious disseminated intravascular coagulation (DIC), with low platelet count (2g/L or low 12sec and/or aPTT > 60sec, presence of fibrin degradation products in the plasma, with or without clinically visible hemorrhagic signs , 4. ARDS of another origin, 5. Concomitant pulmonary infection (pneumoniae) with another agent, notably bacterial or fungal, 6. Patients presenting with hemoglobin < 9g/L, 7. Patients under immunosuppressive agents, 8. Patients receiving an anti-cancer treatment (radiotherapy, chemotherapy, immunotherapy) 9. Patients under aspirin = 100 mg/day, 10. Patients under anticoagulant therapy (except heparin and lowmolecular weight heparin), and anti-Xa drugs achieving effective anticoagulation, as assessed by appropriate tests, or having received thrombolytics =24 hrs, 11. Patients receiving NSAIDs or anti-platelet agents with platelet suppression within the past 7 days, 12. Patients treated concomitantly with another monoclonal antibody (e.g. tocilizumab) 13. Ischemic stroke or transient ischemic attack within the past year, 14. Deep venous thrombosis or pulmonary embolism within the past year, 15. Severe renal insufficiency (Grades 4-5) with a glomerular filtration rate <30mL/Min/1.73m2, 16. One of the following severe organ failures: a. Hepatic with either Child Pugh score =C, or ASAT/ALAT =5 U.N.L, b. Cardiac with NYHA=Class II, unstable angina pectoris, myocardial infarct <1 year, supra-ventricular or ventricular arrhythmia, 17. Hereditary tendency to bleeding or coagulopathy, 18. Severe vascular disease (aneurysms, arterial surgery =6 months), 19. Unhealed wounds, gastrointestinal ulcers or perforation =6 months, 20. Major surgery <28 days, other surgery within the past 7 days, 21. Hemoptysis, GI bleeding, CNS bleeding <1 month, 22. Platelet count <50,000/mm3 (50G/L), 23. Absolute Neutrophil Count =1,000/mm3 (1.0G/L), 24. Terminal illness, including cancer (life expectancy <3 months), 25. Uncontrolled arterial hypertension (systolic blood pressure =185 mmHg and/or diastolic blood pressure =110 mmHg despite appropriate antihypertensive therapy, 26. Childbirth within <10 days, 27. Pregnancy or breastfeeding, 28. Prior cardiopulmonary resuscitation <10 days, 29. Allergy or hypersensitivity to drugs of the same class 30. Participation in another interventional clinical trial within 30 days prior to the inclusion
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the effect of glenzocimab in preventing clinical progression of disease, when added to Standard-of-Care in Covid-19 patients presenting with acute respiratory distress syndrome;Secondary Objective: Efficacy: • To assess the impact of treatment on overall disease control, • To assess the impact of treatment on symptomatology and biological parameters. Safety: • To assess the number of the following events: o deaths, o serious adverse events (SAEs), o suspected unexpected serious adverse reactions (SUSARs) o medically important events, o Bleeding-related events. Pharmacokinetics: • To verify that actual PK profile in patients does not differ from that in healthy volunteers, and matches with PK-PD simulation. Exploratory: • Evolution of pulmonary lesions on chest imaging, • Evolution of biological parameters related to hemostasis, coagulation and inflammation, • Determination of predictive factors for a response.;Primary end point(s): Primary efficacy endpoint: Progression from moderate to severe respiratory distress assessed at Day 4. The primary efficacy endpoint is a composite failure endpoint defined as the occurrence of at least one of the following failure events : o RR = 30/min, or o SpO2 = 90% in resting state, or o PaO2/FiO2 = 100mmHg o Death occurring prior to or on Day 4 ;Timepoint(s) of evaluation of this end point: Cf Figure 5 of the protocol version 3.0 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary efficacy endpoints : • All cause Death at day 40 and Overall Survival • WHO-COVID-19 Scale • NEWS-2 Scale • Respiratory Rate status defined as:: o Normal: 300 mmHg, o Mild: 200 mmHg 95% o Mild: 93% < SpO2 = 95%, o Moderate: 90% < SpO2 = 93%, o Severe: = 90%, o Death. • CHEST CT-Scan (or in exceptional cases, chest radiogram) • oxygen-free days (over the study period = 40 days), • Admission to the ICU (over study period = 40 days), • ICU-free days (over study period = 40 days), • Hospital-free days (over study period = 40 days), • Clinical recovery and Time to Clinical recovery (over study period = 40 days), • Chest CT-Scan, • Cure and Time-to-cure (over study period = 40 days). ;Timepoint(s) of evaluation of this end point: Cf Figure 5 of the protocol version 3.0 | — |
Countries
Brazil, France
Contacts
Public ContactLAURIE JULLIEN
ACTICOR BIOTECH
Outcome results
None listed