Clinical trial NCT04469621: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Corona Virus Infection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2020-07-14
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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.

Primary outcomes:
measure: Relative change from baseline in CRP level
timeFrame: Day 7
Secondary outcomes:
measure: Time to 50% decrease from baseline in CRP level
timeFrame: Baseline to Day 28
measure: Time to improvement of oxygenation
timeFrame: Baseline to Day 28
measure: Change from baseline in SPO2/FiO2 ratio
timeFrame: Day 7
measure: Number of Days without need for oxygen support and alive
timeFrame: Baseline to Day 28
measure: Numbers of Ventilator-free days and alive
timeFrame: Baseline to Day 28
measure: Change from baseline in markers of inflammation: white blood cell count and differential blood lymphocytes
timeFrame: Day 7 and Day 15
measure: Change from baseline in marker of inflammation: neutrophil to lymphocyte ratio
timeFrame: Day 7 and Day 15
measure: Change from baseline in marker of inflammation: interleukin 6 (IL-6)
timeFrame: Day 7 and Day 15
measure: Change from baseline in D-Dimer
timeFrame: Day 7 and Day 15
measure: Incidence of Deaths
timeFrame: Baseline to Day 28
measure: Percentage of participants receiving thrombolytic treatment
timeFrame: Baseline to Day 28
measure: Percentage of participants receiving vasopressor treatment
timeFrame: Baseline to Day 28
measure: Incidence of serious adverse events (SAEs), adverse events of special interest (AESI) and treatment-emergent adverse events (TEAEs) leading to treatment discontinuation
timeFrame: Baseline to Day 28
measure: Incidence of TEAEs leading to study discontinuation (primary reason)
timeFrame: Baseline to Day 28
measure: Numbers of Respiratory Failure-Free Days (RFFD) and alive
timeFrame: Baseline to Day 28
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Investigational Site Number 0320001
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 0760003
city: São José Do Rio Preto
country: Brazil
facility: Investigational Site Number 0760001
city: São Paulo
country: Brazil
facility: Investigational Site Number 0760002
city: Santiago
country: Chile
facility: Investigational Site Number 1520001
city: Santiago
country: Chile
facility: Investigational Site Number 1520003
city: Talca
country: Chile
facility: Investigational Site Number 1520002
city: Monterrey
country: Mexico
facility: Investigational Site Number 4840001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430002
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References: