Corona Virus Infection
Conditions
Brief summary
Primary Objective: To evaluate the effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by C-reactive protein (CRP) levels in adult patients hospitalized with severe coronavirus disease 2019 (COVID-19) Secondary Objectives: * To evaluate the time to onset of effect of SAR443122 relative to the control arm on the hyperinflammatory state as measured by CRP levels * To evaluate the time to onset of effect of SAR443122 relative to the control arm on oxygenation status * To evaluate the effect of SAR443122 relative to the control arm on oxygenation status * To evaluate the effect of SAR443122 relative to the control arm on total duration of supplemental oxygen requirement * To evaluate the effect of SAR443122 relative to the control arm on length of ventilator support needed * To evaluate the effect of SAR443122 relative to the control arm on laboratory markers of severe COVID-19 * To evaluate the effect of SAR443122 relative to the control arm on mortality * To evaluate the effect of SAR443122 relative to the control arm on need for thrombolytic therapy * To evaluate the effect of SAR443122 relative to the control arm on need for vasopressor treatment * To evaluate the safety of SAR443122 as compared to the control arm up to End of Study * To evaluate the effect of SAR443122 relative to the control arm on total duration without high flow supplemental oxygen requirements
Detailed description
Study duration per participant is approximatively 32 days including a 14-day treatment period
Interventions
DRUGSAR443122
Pharmaceutical form:capsule Route of administration: oral
DRUGPlacebo
Pharmaceutical form:capsule Route of administration: oral
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Participant must be ≥18 years and ≤80 years of age inclusive, at the time of signing the informed consent. * Hospitalized (or documentation of a plan to admit to the hospital if the participant is in an emergency department) with evidence of COVID-19 lung disease diagnosed by chest radiograph, chest computed tomography or chest auscultation (rales, crackles) and with severe disease defined as follows: The participant requires supplemental oxygen administered by nasal cannula, simple face mask, or other similar oxygen delivery device (ie, increase in oxygen requirement following SARS-CoV-2 infection). * SARS-CoV-2 infection confirmed by RT-PCR, or other commercial or public health assay in any specimen, within 3 weeks prior to randomization, and no alternative explanation for current clinical condition. * At time of randomization, have demonstrated laboratory signs consistent with systemic inflammation. * Male and/or female participants, including women of childbearing potential (WOCBP). * Capable of giving signed informed consent.
Exclusion criteria
* In the opinion of the investigator, unlikely to survive after 48 hours, or unlikely to remain at the investigational site beyond 48 hours * Participants requiring use of invasive or non-invasive positive pressure ventilation at randomization. * Presence of significant liver enzyme abnormalities, thrombocytopenia or anemia at screening. * Any prior or concurrent use or plans to receive during the study period of immunomodulatory therapies (other than interventional drug) at screening. * Use of chronic systemic corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day at screening. *
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Relative change from baseline in CRP level | Day 7 | Relative change from baseline in CRP level on Day 7 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to improvement of oxygenation | Baseline to Day 28 | The time to improvement of oxygenation as measured by oxygen saturation \>/=92% breathing room air over 48 hrs or until discharge |
| Change from baseline in SPO2/FiO2 ratio | Day 7 | Change from baseline in SPO2/FiO2 ratio at Day 7 |
| Number of Days without need for oxygen support and alive | Baseline to Day 28 | Number of Days without need for oxygen support and alive (oxygen saturation \>=92% breathing room air) up to Day 28 |
| Numbers of Ventilator-free days and alive | Baseline to Day 28 | Numbers of Ventilator-free days and alive up to Day 28 |
| Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes | Day 7 and Day 15 | Change from baseline in white blood cell count and differential blood lymphocytes at Day 7 and End of treatment (EOT) |
| Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio | Day 7 and Day 15 | Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT |
| Change from baseline in marker of inflammation: interleukin 6 (IL-6) | Day 7 and Day 15 | Change from baseline in IL-6 at Day 7 and EOT |
| Time to 50% decrease from baseline in CRP level | Baseline to Day 28 | The time to 50% decrease from baseline in CRP level |
| Incidence of Deaths | Baseline to Day 28 | Incidence of Deaths up to Day 28 |
| Percentage of participants receiving thrombolytic treatment | Baseline to Day 28 | Percentage of participants receiving thrombolytic treatment up to Day 28 |
| Percentage of participants receiving vasopressor treatment | Baseline to Day 28 | Percentage of participants receiving vasopressor treatment up to Day 28 |
| Incidence of serious adverse events (SAEs), adverse events of special interest (AESI) and treatment-emergent adverse events (TEAEs) leading to treatment discontinuation | Baseline to Day 28 | — |
| Incidence of TEAEs leading to study discontinuation (primary reason) | Baseline to Day 28 | — |
| Numbers of Respiratory Failure-Free Days (RFFD) and alive | Baseline to Day 28 | Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28 |
| Change from baseline in D-Dimer | Day 7 and Day 15 | Change from baseline in D-Dimer at Day 7 and EOT |
Countries
Argentina, Brazil, Chile, Mexico, Russia
Outcome results
None listed