Sarilumab COVID-19

NCT04327388 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: EFC168442020-001162-12U1111-1249-6021
• Study Type: interventional
• Target: 420
• Locations: 11 countries
• Sites: 47

Brief Summary

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.

Conditions

Corona Virus Infection

Outcome Measures

Primary Outcomes (1)

• Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points

  Time to improvement of greater than or equal (\>=) 2 points in clinical status assessment was defined as time (in days) from first dose of study drug to the time of first occurrence of improvement of \>=2 points in clinical status of participants assessed using 7-point ordinal scale (calculated as: Date of first occurrence/episode of the event - date of first dose + 1). Seven-point ordinal scale for clinical assessment ranges from 1= death; 2= hospitalized, on invasive mechanical ventilation/ECMO; 3= hospitalized, on non-invasive ventilation/high flow oxygen devices; 4= hospitalized, requiring supplemental oxygen; 5= hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related/otherwise); 6= hospitalized, not requiring supplemental oxygen - no longer required ongoing medical care; 7= not hospitalized, higher score = less severity. Kaplan-Meier method was used for analysis.

  Baseline to Day 29

Secondary Outcomes (27)

• Percentage of Participants Who Were Alive at Day 29

  Day 29

• Percentage of Participants With Improvement in Clinical Status (According to 7-point Ordinal Scale Score) by at Least 1 Point From Baseline at Days 4, 7, 15, 21, and 29

  Baseline, Days 4, 7, 15, 21, and 29

• Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score

  Baseline, Days 4, 7, 15, 21, and 29

• Time to Resolution of Fever

  Baseline to Day 29

• Time to Resolution of Fever and Improvement in Oxygenation

  Baseline to Day 29

Study Arms (3)

Sarilumab 200 mg

EXPERIMENTAL

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.

Drug: Sarilumab SAR153191

Sarilumab 400 mg

EXPERIMENTAL

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.

Drug: Sarilumab SAR153191

Placebo

PLACEBO COMPARATOR

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.

Drug: Placebo

Interventions

Sarilumab SAR153191 DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion

Also known as: REGN88, Kevzara®

Sarilumab 200 mg; Sarilumab 400 mg

Placebo DRUG

Pharmaceutical form: Solution for injection Route of administration: Intravenous infusion

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sanofi: lead
• Regeneron Pharmaceuticals: collaborator

Study Sites (47)

Investigational Site Number 0320001

Caba, 1430, Argentina

Location

Investigational Site Number 0320003

Caba, C1180AAX, Argentina

Location

Investigational Site Number 0320004

Caba, C1426AAM, Argentina

Location

Investigational Site Number 0760003

Porto Alegre, 90110-270, Brazil

Location

Investigational Site Number 0760004

São José do Rio Preto, 15090-000, Brazil

Location

Investigational Site Number 0760001

São Paulo, 01327-001, Brazil

Location

Investigational Site Number 0760002

São Paulo, 04231-030, Brazil

Location

Investigational Site Number 0760005

São Paulo, 04321-120, Brazil

Location

Investigational Site Number 1240001

Montreal, H2X3E4, Canada

Location

Investigational Site Number 1240005

Montreal, H4A 3J1, Canada

Location

Investigational Site Number 1240004

Toronto, M4N3M5, Canada

Location

Investigational Site Number 1240002

Toronto, M5G 2N2, Canada

Location

Investigational Site Number 1240003

Vancouver, V5Z 1M9, Canada

Location

Investigational Site Number 1520003

Santiago, 750-0691, Chile

Location

Investigational Site Number 1520002

Santiago, 80004005, Chile

Location

Investigational Site Number 1520004

Santiago, Chile

Location

Investigational Site Number 1520001

Talca, 3460001, Chile

Location

Investigational Site Number 2500001

Bordeaux, 33076, France

Location

Investigational Site Number 2500007

Clamart, 92140, France

Location

Investigational Site Number 2500006

La Roche-sur-Yon, 85925, France

Location

Investigational Site Number 2500002

Nantes, 44093, France

Location

Investigational Site Number 2500005

Paris, 75877, France

Location

Investigational Site Number 2500003

Strasbourg, 67098, France

Location

Investigational Site Number 2500004

Suresnes, 92151, France

Location

Investigational Site Number 2760004

Cologne, 50937, Germany

Location

Investigational Site Number 2760002

Essen, 45147, Germany

Location

Investigational Site Number 2760001

Münster, 48149, Germany

Location

Investigational site number 3760003

Ashdod, 7747629, Israel

Location

Investigational Site Number 3760002

Jerusalem, 91120, Israel

Location

Investigational Site Number 3760001

Ramat Gan, 52662, Israel

Location

Investigational Site Number 3800005

Milan, 20122, Italy

Location

Investigational Site Number 3800001

Milan, 20132, Italy

Location

Investigational Site Number 3800002

Milan, 20157, Italy

Location

Investigational Site Number 3800003

Modena, 41100, Italy

Location

Investigational Site Number 3800004

Parma, 43100, Italy

Location

Investigational Site Number 3800006

Rozzano, 20089, Italy

Location

Investigational Site Number 3920002

Fuchu-Shi, Japan

Location

Investigational Site Number 3920003

Iruma-Gun, Japan

Location

Investigational Site Number 3920001

Kamakura-Shi, Japan

Location

Investigational Site Number 6430003

Moscow, 111539, Russia

Location

Investigational Site Number 6430002

Moscow, 123182, Russia

Location

Investigational Site Number 6430001

Moscow, 129301, Russia

Location

Investigational Site Number 7240003

Barcelona, 08035, Spain

Location

Investigational Site Number 7240004

Barcelona, 08036, Spain

Location

Investigational Site Number 7240002

Madrid, 28007, Spain

Location

Investigational Site Number 7240005

Madrid, 28034, Spain

Location

Investigational Site Number 7240001

Madrid, 28046, Spain

Location

Related Publications (1)

• Lescure FX, Honda H, Fowler RA, Lazar JS, Shi G, Wung P, Patel N, Hagino O; Sarilumab COVID-19 Global Study Group. Sarilumab in patients admitted to hospital with severe or critical COVID-19: a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Respir Med. 2021 May;9(5):522-532. doi: 10.1016/S2213-2600(21)00099-0. Epub 2021 Mar 4.

  PMID: 33676590 DERIVED

Related Links

• EFC16844 Plain Language Results Summary

MeSH Terms

Conditions

Coronavirus Infections

Interventions

sarilumab

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Trial Transparency Team
• Organization: Sanofi

Contact-US@sanofi.com

800-633-1610

Study Officials

• Clinical Sciences & Operations

  Sanofi

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 26, 2020
• First Posted: March 31, 2020
• Study Start: March 28, 2020
• Primary Completion: July 31, 2020
• Study Completion: September 2, 2020
• Last Updated: September 24, 2025
• Results First Posted: May 13, 2021

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share

Locations

IT (6); DE (3); AR (3); ES (5); RU (3); JP (3); IL (3); BR (5); CL (4); CA (5); FR (7)