A Phase 1b Trial to Evaluate Safety and Effect of SAR443122 on Immune System in Severe COVID-19

Sanofi68 enrolled

Overview

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

Study duration per participant is approximatively 32 days including a 14-day treatment period

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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. * Exclusion criteria related to tuberculosis (TB) and non-tuberculous mycobacterial (NTM) infections. * Participants with suspected or known active systemic bacterial or fungal infections within 4 weeks of screening. * Pregnant or breastfeeding women. * In the opinion of the study investigator, might confound the results of the study or pose an undue risk to the safety of the participant. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Locations (10)

Investigational Site Number 0320001

Caba, Argentina

Investigational Site Number 0760003

Porto Alegre, Brazil

Investigational Site Number 0760001

São José do Rio Preto, Brazil

Investigational Site Number 0760002

São Paulo, Brazil

Investigational Site Number 1520001

Santiago, Chile

Investigational Site Number 1520003

Santiago, Chile

Investigational Site Number 1520002

Talca, Chile

Investigational Site Number 4840001

Monterrey, Mexico

Investigational Site Number 6430001

Moscow, Russia

Investigational Site Number 6430002

Moscow, Russia

Outcomes

Primary Outcomes

Relative change from baseline in CRP level

Relative change from baseline in CRP level on Day 7

Time frame: Day 7

Secondary Outcomes

Time to 50% decrease from baseline in CRP level

The time to 50% decrease from baseline in CRP level

Time frame: Baseline to Day 28

Time to improvement of oxygenation

The time to improvement of oxygenation as measured by oxygen saturation \>/=92% breathing room air over 48 hrs or until discharge

Time frame: Baseline to Day 28

Change from baseline in SPO2/FiO2 ratio

Change from baseline in SPO2/FiO2 ratio at Day 7

Time frame: Day 7

Number of Days without need for oxygen support and alive

Number of Days without need for oxygen support and alive (oxygen saturation \>=92% breathing room air) up to Day 28

Time frame: Baseline to Day 28

Numbers of Ventilator-free days and alive

Numbers of Ventilator-free days and alive up to Day 28

Time frame: Baseline to Day 28

Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes

Change from baseline in white blood cell count and differential blood lymphocytes at Day 7 and End of treatment (EOT)

Time frame: Day 7 and Day 15

Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio

Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT

Time frame: Day 7 and Day 15

Change from baseline in marker of inflammation: interleukin 6 (IL-6)

Change from baseline in IL-6 at Day 7 and EOT

Time frame: Day 7 and Day 15

Change from baseline in D-Dimer

Change from baseline in D-Dimer at Day 7 and EOT

Time frame: Day 7 and Day 15

Incidence of Deaths

Incidence of Deaths up to Day 28

Time frame: Baseline to Day 28

Percentage of participants receiving thrombolytic treatment

Percentage of participants receiving thrombolytic treatment up to Day 28

Time frame: Baseline to Day 28

Percentage of participants receiving vasopressor treatment

Percentage of participants receiving vasopressor treatment up to Day 28

Time frame: Baseline 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

Time frame: Baseline to Day 28

Incidence of TEAEs leading to study discontinuation (primary reason)

Time frame: Baseline to Day 28

Numbers of Respiratory Failure-Free Days (RFFD) and alive

Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28

Time frame: Baseline to Day 28

A Phase 1b Trial to Evaluate Safety and Effect of SAR443122 on Immune System in Severe COVID-19

Overview

Conditions

Interventions

Eligibility

Locations (10)

Outcomes

Primary Outcomes

Secondary Outcomes