Sarilumab COVID-19

Sanofi

Status and phase: Completed; Phase 3

Conditions: Corona Virus Infection

Treatments: Drug: Placebo; Drug: Sarilumab SAR153191

Study type: Interventional

Funder types: Industry

Identifiers

NCT04327388

EFC16844

2020-001162-12 (EudraCT Number)

U1111-1249-6021 (Other Identifier)

Details and patient eligibility

About

Primary Objective:

To evaluate the clinical efficacy of sarilumab relative to the control arm in adult participants hospitalized with severe or critical Coronavirus Disease 2019 (COVID-19).

Secondary Objectives:

• Evaluate the 28-day survival rate.

• Evaluate the clinical efficacy of sarilumab compared to the control arm by clinical severity.

• Evaluate changes in the National Early Warning Score 2.

• Evaluate the duration of predefined symptoms and signs (if applicable).

• Evaluate the duration of supplemental oxygen dependency (if applicable).

• Evaluate the incidence of new mechanical ventilation use during the study.

• Evaluate the duration of new mechanical ventilation use during the Study.

• Evaluate the proportion of participants requiring rescue medication during the 28-day period.

• Evaluate need for admission into intensive care unit.

• Evaluate duration of hospitalization (days).

• The secondary safety objectives of the study were to evaluate the safety of sarilumab through hospitalization (up to Day 29 if participant was still hospitalized) compared to the control arm as assessed by incidence of:

  • Serious adverse events.
  • Major or opportunistic bacterial or fungal infections in participants with grade 4 neutropenia.
  • Grade greater than or equal to (>=) 2 infusion related reactions.
  • Grade >=2 hypersensitivity reactions.
  • Increase in alanine transaminase (ALT) >=3X upper limit of normal (ULN) (for participants with normal baseline) or greater than 3X ULN AND at least 2-fold increase from baseline value (for participants with abnormal baseline).
  • Major or opportunistic bacterial or fungal infections.

Full description

An individual participant would complete the study approximately 60 days from screening to follow-up on day 60 ±7 days.

Enrollment: 420 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria :

Participants must be >=18 years of age. Participants must be hospitalized for less than or equal to 7 days with evidence of pneumonia and have one of the following disease categories: severe disease or critical disease.

Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection.

Exclusion criteria:

Unlikely to survive after 48 hours from screening or unlikely to remain at the investigational site beyond 48 hours. Participants with multi organ dysfunction or requiring extracorporeal life support or renal replacement therapy were excluded.

Presence of neutropenia less than 2000/cubic millimeter (mmˆ3), aspartate transaminase or ALT greater than 5X ULN, platelets less than 50,000/mmˆ3.

Prior immunosuppressive therapies. Use of systemic chronic corticosteroids for non-COVID-19 related condition. Known or suspected history of tuberculosis. Suspected or known active systemic bacterial or fungal infections.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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420 participants in 3 patient groups, including a placebo group

Sarilumab 200 mg

Experimental group

Description:

Sarilumab 200 milligrams (mg), single dose of intravenous (IV) injection on Day 1. Participants could receive a second dose of sarilumab 200 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 \[dated 08-Apr-2020\]): * Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and * Increase/recurrence of fever or * Increase/no change in fraction of inspired oxygen (FiO2) requirement or * Required vasopressors, extracorporeal membrane oxygenation (ECMO) or development of multi-organ dysfunction.

Treatment:

Drug: Sarilumab SAR153191

Sarilumab 400 mg

Experimental group

Description:

Sarilumab 400 mg, single dose of IV injection on Day 1. Participants could receive a second dose of sarilumab 400 mg 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 \[dated 08-Apr-2020\]): * Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and * Increase/recurrence of fever or * Increase/no change in FiO2 requirement or * Required vasopressors, ECMO or development of multi-organ dysfunction.

Treatment:

Drug: Sarilumab SAR153191

Placebo

Placebo Comparator group

Description:

Placebo (for sarilumab), single dose of IV injection on Day 1. Participants could receive a second dose of placebo (for sarilumab) 24 to 48 hours after the first dose if first and any one of last three criteria was met as compared to Day 1 (as per following protocol amendment 2 \[dated 08-Apr-2020\]): * Benefit risk assessment by the investigator favored the administration of another dose of study drug without compromising safety and * Increase/recurrence of fever or * Increase/no change in FiO2 requirement or * Required vasopressors, ECMO or development of multi-organ dysfunction.

Treatment:

Drug: Placebo