Infection with SARS-CoV-2 virus, COVID-19 infection
Conditions
Sponsors
ABIVAX
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A patient will be eligible to participate in this study if ALL the following criteria are met: 1. Adult (= 18 years old) men or women hospitalizedor not hospitalized, diagnosed for SARS-CoV-2 infection by PCR or Rapid Antigen tests (approximately 48 hours prior to randomization), with at least one associated risk factor. Considered risk factors are: • Age = 65 years • Obesity defined as BMI = 30 • Recent histroy of uncontrolled High Blood Pressure • Treated diabetes (type I or II) • History of ischemic cardiovascular disease 2. Symptomatic patients must present at least 1 of the following symptoms at enrollment: fever or perceived fever ( for more than 24 hours, headache, sore throat, dry cough, fatigue, chest pain or choking sensation (with no associated respiratory distress), myalgia, anosmia, ageusia or gastro-intestinal symptoms. 3. Patients with pulse oximetry arterial saturation (SpO2) = 92 % on room air at enrolment. 4. Patients with the following hematological and biochemical laboratory parameters obtained within 7 days prior to D0: • Hemoglobin > 9.0 g dL-1 • Absolute Neutrophil Count = 1000 mm-3; • Platelets = 100,000 mm-3; • Creatinine clearance = 50 mL min-1 by the Cockcroft-Gault formula • Total serum bilirubin < 2 x ULN • Alkaline phosphatase< 2 x ULN, AST (SGOT) and ALT (SGPT) < 3 x ULN; 5. Women of childbearing potential and men receiving the study treatment and their partners must agree to use a highly effective contraceptive method during the study and for 6 months (180 days) after end of study or early termination. Contraception should be in place at least 2 weeks prior to enrolment. Women must be surgically sterile or if of childbearing potential must use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one month between menstruations) confirmation of absence of pregnancy is required. This recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. Female and male patients must not be planning pregnancy during the trial and for 6 months post completion of their participation in the trial. In addition, male patients should use condom during the trial and for 6 months (180 days) post completion of their participation in the study. Male patients must not donate sperm as long as contraception is required. For the purpose of this protocol, a woman is considered of childbearing potential (WOCBP), i.e. fertile, following menarche and until becoming post-menopausal unless permanently sterile. Permanent sterilisation methods include hysterectomy, bilateral salpingectomy and bilateral oophorectomy. A postmenopausal state is defined as no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a post-menopausal state in women not using hormonal contraception or hormonal replacement therapy. However, in the absence of 12 months of amenorrhea, a single FSH measurement is insuffici
Exclusion criteria
Exclusion criteria: Patients who meet any of the following exclusion criteria will be excluded from the study: 1. Patients with moderate or severe acute respiratory failure or requiring non-invasive ventilation or oxygen or with SpO2 < 92% or tachypnea (respiratory rate = 30 breaths/min). 2. Patients treated with immunosuppressors and/or immunomodulators (cf. Appendix #2). 3. Engrafted patients (organ and/or hematopoietic stem cells). 4. Patients with uncontrolled auto-immune disease. 5. Patients with known or suspected active (i.e. not controlled) bacterial, viral (excluding COVID-19) or fungal infections. 6. Patients with preexisting, severe and not controlled organ failure. 7. History or active malignancy requiring chemotherapy or radiation therapy (excluding 2 years disease free survivor patients). 8. Pregnant or breast-feeding women. 9. Illicit drug or alcohol abuse or dependence that may compromise the patient's safety or adherence to the study protocol. 10. Use of any investigational or non-registered product within 3 months or within 5 half-lives preceding baseline, whichever is longer. 11. Hypersensitivity to ABX464 and/or its excipients. 12. Any condition, which in the opinion of the investigator, could compromise the patient's safety or adherence to the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the efficacy of ABX464 50mg to prevent respiratory failure or death in study patients.;Secondary Objective: Evaluate the proportion of patients requiring hospitalization compared to the {Standard of care + placebo} group Assess the proportion of patients reporting each severity rating on a 7-point ordinal scale Assess the time to an improvement of one category of the a 7-point on an ordinal scale from baseline Evaluate and compare the effect of ABX464 on immunophenotyping and cytokines levels Evaluate the proportion of patient requiring oxygen supplementation Assess the time to hospitalization Evaluate the time to application of invasive and non-invasive mechanical ventilation or high flow oxygen therapy Assess the IMV and/or NIV duration Assess the oxygen supplementation (>3L/min) duration Assess the hospital stay duration Evaluate the effect of ABX464 on miR-124 expression Assess the change in CRP, Troponin I & T and D-dimer levels Evaluate the prevention of Covid-19 related deaths Evaluate SARS-CoV-2 infection in subjects Evaluate the safety ;Primary end point(s): ?Rate of patients with no invasive or non-invasive mechanical ventilation (IMV and NIV, respectively), but excluding simple nasal/mask oxygen supplementation, and who are alive at the end of the 28 days period.;Timepoint(s) of evaluation of this end point: Day 28 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.Rate of patients hospitalized 2. Percentage of patients reporting each severity rating on a 7-point ordinal scale at each study visit (i.e. Not hospitalized, no limitations on activities; Not hospitalized, limitation on activities; Hospitalized, not requiring supplemental oxygen; Hospitalized, requiring supplemental oxygen; Hospitalized, on non-invasive ventilation or high flow oxygen devices; Hospitalized, on invasive mechanical ventilation or ECMO; Death); 3.Change in the ranking on an ordinal scale from baseline to days 7, 14, 21, 28, 48 and at 4 month 4.Change from enrolment in inflammatory markers in plasma (i.e. MCP-1, MIP-1 a, G-CSF, IL-1b, IL-2, IL-6, IL-7, IL-10, IL-17, INFg and TNFa) and in immune phenotype and assessment of cell-activation markers in PBMCs at D14, D28. 5.Rate of patients requiring oxygen supplementation. 6.Time to hospitalization from baseline. 7.Time to assisted ventilation and oxygen supplementation (log rank) from baseline. 8.Number of days of assisted ventilation. 9.Number of days of oxygen supplementation. 10.Number of days at the hospital from admission to discharge. 11.Change from baseline in microRNA-124 levels in total blood (PAXgene®) at D0, D7 and D28. 12.AUC and % of change from enrolment in CRP, Troponin I & T and D-dimer levels. 13.Time to death and mortality rate (all causes, and Covid-19 related). 14. To evaluate the improvement the 7-point ordinal scale during the course of the study compared to {Standard of care + placebo} group. 15. Time to improvement of one level in é-point ordinal scale. 16.SARS-CoV-2 virus in nasopharyngeal sample and/or in blood at Day 0, 7, 14, 21, and 28. 17.Number and rates of participants with Treatment Emergent Adverse Event 18.Cumulative incidence of serious adverse events (SAEs) including serious adverse drug reactions (SARs) and suspected unexpected serious adverse reactions (SUSARs) 19.Cumulative incidence of Grade 3 and 4 adverse events (AEs) | — |
Countries
Belgium, Brazil, Chile, France, Germany, Italy, Mexico, Peru, Spain, United Kingdom
Contacts
Public ContactClinical operations
abivax
Outcome results
None listed