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

A Phase 1b, Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Immunomodulatory Effect of the RIPK1 Inhibitor SAR443122 in Hospitalized Patients With Severe COVID-19

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 Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: SAR443122; Drug: Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 1

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, 1430
    • Investigational Site Number 0320001
• Brazil
  • Porto Alegre, Brazil, 90035 003
    • Investigational Site Number 0760003
  • São José Do Rio Preto, Brazil, 15090-000
    • Investigational Site Number 0760001
  • São Paulo, Brazil, 04321-120
    • Investigational Site Number 0760002
• Chile
  • Santiago, Chile, 750-0691
    • Investigational Site Number 1520001
  • Santiago, Chile, 8900085
    • Investigational Site Number 1520003
  • Talca, Chile, 3460001
    • Investigational Site Number 1520002
• Mexico
  • Monterrey, Mexico, 64460
    • Investigational Site Number 4840001
• Russian Federation
  • Moscow, Russian Federation, 111539
    • Investigational Site Number 6430001
  • Moscow, Russian Federation, 123182
    • Investigational Site Number 6430002

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; matching placebo	Drug: Placebo; Pharmaceutical form:capsule Route of administration: oral
Experimental: SAR443122; SAR443122 dose 1, twice daily for 14 days	Drug: SAR443122; Pharmaceutical form:capsule Route of administration: oral

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Relative change from baseline in CRP level	Relative change from baseline in CRP level on Day 7	Day 7

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to 50% decrease from baseline in CRP level	The time to 50% decrease from baseline in CRP level	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	Baseline to Day 28
Change from baseline in SPO2/FiO2 ratio	Change from baseline in SPO2/FiO2 ratio at Day 7	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	Baseline to Day 28
Numbers of Ventilator-free days and alive	Numbers of Ventilator-free days and alive up to Day 28	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)	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	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	Day 7 and Day 15
Change from baseline in D-Dimer	Change from baseline in D-Dimer at Day 7 and EOT	Day 7 and Day 15
Incidence of Deaths	Incidence of Deaths up to Day 28	Baseline to Day 28
Percentage of participants receiving thrombolytic treatment	Percentage of participants receiving thrombolytic treatment up to Day 28	Baseline to Day 28
Percentage of participants receiving vasopressor treatment	Percentage of participants receiving vasopressor treatment up to Day 28	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		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	Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28	Baseline to Day 28

Collaborators and Investigators

• Sponsor: Sanofi

Study record dates

Study Major Dates

• Study Start (Actual): July 17, 2020
• Primary Completion (Actual): October 23, 2020
• Study Completion (Actual): October 23, 2020

Study Registration Dates

• First Submitted: June 28, 2020
• First Submitted That Met QC Criteria: July 12, 2020
• First Posted (Actual): July 14, 2020

Study Record Updates

• Last Update Posted (Actual): April 25, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections
• Other Study ID Numbers: PDY16879; 2020-002104-39 (EudraCT Number); U1111-1250-1185 (Other Identifier: UTN)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Qualified researchers may request access to patient level data and related study documents including the clinical study report, study protocol with any amendments, blank case report form, statistical analysis plan, and dataset specifications. Patient level data will be anonymized and study documents will be redacted to protect the privacy of trial participants. Further details on Sanofi's data sharing criteria, eligible studies, and process for requesting access can be found at: https://vivli.org

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No