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

Primary Purpose

Corona Virus Infection

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
SAR443122
Placebo
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Corona Virus Infection

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Investigational Site Number 0320001
  • Investigational Site Number 0760003
  • Investigational Site Number 0760001
  • Investigational Site Number 0760002
  • Investigational Site Number 1520001
  • Investigational Site Number 1520003
  • Investigational Site Number 1520002
  • Investigational Site Number 4840001
  • Investigational Site Number 6430001
  • Investigational Site Number 6430002

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

SAR443122

Placebo

Arm Description

SAR443122 dose 1, twice daily for 14 days

matching placebo

Outcomes

Primary Outcome Measures

Relative change from baseline in CRP level
Relative change from baseline in CRP level on Day 7

Secondary Outcome Measures

Time to 50% decrease from baseline in CRP level
The time to 50% decrease from baseline in CRP level
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
Change from baseline in SPO2/FiO2 ratio
Change from baseline in SPO2/FiO2 ratio at 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
Numbers of Ventilator-free days and alive
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
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
Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT
Change from baseline in marker of inflammation: interleukin 6 (IL-6)
Change from baseline in IL-6 at Day 7 and EOT
Change from baseline in D-Dimer
Change from baseline in D-Dimer at Day 7 and EOT
Incidence of Deaths
Incidence of Deaths up to Day 28
Percentage of participants receiving thrombolytic treatment
Percentage of participants receiving thrombolytic treatment up to Day 28
Percentage of participants receiving vasopressor treatment
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
Incidence of TEAEs leading to study discontinuation (primary reason)
Numbers of Respiratory Failure-Free Days (RFFD) and alive
Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28

Full Information

First Posted
June 28, 2020
Last Updated
April 21, 2022
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT04469621
Brief Title
A Phase 1b Trial to Evaluate Safety and Effect of SAR443122 on Immune System in Severe COVID-19
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
July 17, 2020 (Actual)
Primary Completion Date
October 23, 2020 (Actual)
Study Completion Date
October 23, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corona Virus Infection

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
SAR443122
Arm Type
Experimental
Arm Description
SAR443122 dose 1, twice daily for 14 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo
Intervention Type
Drug
Intervention Name(s)
SAR443122
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Pharmaceutical form:capsule Route of administration: oral
Primary Outcome Measure Information:
Title
Relative change from baseline in CRP level
Description
Relative change from baseline in CRP level on Day 7
Time Frame
Day 7
Secondary Outcome Measure Information:
Title
Time to 50% decrease from baseline in CRP level
Description
The time to 50% decrease from baseline in CRP level
Time Frame
Baseline to Day 28
Title
Time to improvement of oxygenation
Description
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
Title
Change from baseline in SPO2/FiO2 ratio
Description
Change from baseline in SPO2/FiO2 ratio at Day 7
Time Frame
Day 7
Title
Number of Days without need for oxygen support and alive
Description
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
Title
Numbers of Ventilator-free days and alive
Description
Numbers of Ventilator-free days and alive up to Day 28
Time Frame
Baseline to Day 28
Title
Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes
Description
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
Title
Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio
Description
Change from baseline in neutrophil to lymphocyte ratio at Day 7 and EOT
Time Frame
Day 7 and Day 15
Title
Change from baseline in marker of inflammation: interleukin 6 (IL-6)
Description
Change from baseline in IL-6 at Day 7 and EOT
Time Frame
Day 7 and Day 15
Title
Change from baseline in D-Dimer
Description
Change from baseline in D-Dimer at Day 7 and EOT
Time Frame
Day 7 and Day 15
Title
Incidence of Deaths
Description
Incidence of Deaths up to Day 28
Time Frame
Baseline to Day 28
Title
Percentage of participants receiving thrombolytic treatment
Description
Percentage of participants receiving thrombolytic treatment up to Day 28
Time Frame
Baseline to Day 28
Title
Percentage of participants receiving vasopressor treatment
Description
Percentage of participants receiving vasopressor treatment up to Day 28
Time Frame
Baseline to Day 28
Title
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
Title
Incidence of TEAEs leading to study discontinuation (primary reason)
Time Frame
Baseline to Day 28
Title
Numbers of Respiratory Failure-Free Days (RFFD) and alive
Description
Numbers of Respiratory Failure-Free Days (RFFD) and alive up to Day 28
Time Frame
Baseline to Day 28

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Sciences & Operations
Organizational Affiliation
Sanofi
Official's Role
Study Director
Facility Information:
Facility Name
Investigational Site Number 0320001
City
Caba
ZIP/Postal Code
1430
Country
Argentina
Facility Name
Investigational Site Number 0760003
City
Porto Alegre
ZIP/Postal Code
90035 003
Country
Brazil
Facility Name
Investigational Site Number 0760001
City
São José Do Rio Preto
ZIP/Postal Code
15090-000
Country
Brazil
Facility Name
Investigational Site Number 0760002
City
São Paulo
ZIP/Postal Code
04321-120
Country
Brazil
Facility Name
Investigational Site Number 1520001
City
Santiago
ZIP/Postal Code
750-0691
Country
Chile
Facility Name
Investigational Site Number 1520003
City
Santiago
ZIP/Postal Code
8900085
Country
Chile
Facility Name
Investigational Site Number 1520002
City
Talca
ZIP/Postal Code
3460001
Country
Chile
Facility Name
Investigational Site Number 4840001
City
Monterrey
ZIP/Postal Code
64460
Country
Mexico
Facility Name
Investigational Site Number 6430001
City
Moscow
ZIP/Postal Code
111539
Country
Russian Federation
Facility Name
Investigational Site Number 6430002
City
Moscow
ZIP/Postal Code
123182
Country
Russian Federation

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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

Learn more about this trial

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

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