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

Corona Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04469621
• Other study ID #: PDY16879
• Secondary ID: 2020-002104-39U1
• Status: Completed
• Phase: Phase 1
• Start date: July 17, 2020
• Est. completion date: October 23, 2020

Study information

• Verified date: April 2022
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: October 23, 2020
• Est. primary completion date: October 23, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections

Intervention

Drug:
• SAR443122
Pharmaceutical form:capsule Route of administration: oral
• Placebo
Pharmaceutical form:capsule Route of administration: oral

Locations

Country	Name	City	State
Argentina	Investigational Site Number 0320001	Caba
Brazil	Investigational Site Number 0760003	Porto Alegre
Brazil	Investigational Site Number 0760001	São José Do Rio Preto
Brazil	Investigational Site Number 0760002	São Paulo
Chile	Investigational Site Number 1520001	Santiago
Chile	Investigational Site Number 1520003	Santiago
Chile	Investigational Site Number 1520002	Talca
Mexico	Investigational Site Number 4840001	Monterrey
Russian Federation	Investigational Site Number 6430001	Moscow
Russian Federation	Investigational Site Number 6430002	Moscow

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Argentina,  Brazil,  Chile,  Mexico,  Russian Federation, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative change from baseline in CRP level	Relative change from baseline in CRP level on Day 7	Day 7
Secondary	Time to 50% decrease from baseline in CRP level	The time to 50% decrease from baseline in CRP level	Baseline to Day 28
Secondary	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
Secondary	Change from baseline in SPO2/FiO2 ratio	Change from baseline in SPO2/FiO2 ratio at Day 7	Day 7
Secondary	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
Secondary	Numbers of Ventilator-free days and alive	Numbers of Ventilator-free days and alive up to Day 28	Baseline to Day 28
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in D-Dimer	Change from baseline in D-Dimer at Day 7 and EOT	Day 7 and Day 15
Secondary	Incidence of Deaths	Incidence of Deaths up to Day 28	Baseline to Day 28
Secondary	Percentage of participants receiving thrombolytic treatment	Percentage of participants receiving thrombolytic treatment up to Day 28	Baseline to Day 28
Secondary	Percentage of participants receiving vasopressor treatment	Percentage of participants receiving vasopressor treatment up to Day 28	Baseline to Day 28
Secondary	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
Secondary	Incidence of TEAEs leading to study discontinuation (primary reason)		Baseline to Day 28
Secondary	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