Either you have JavaScript disabled or your browser does not support Javascript . To work properly, this page requires JavaScript to be enabled.
How to enable JavaScript in your browser?

An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19

Trial Profile

An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19

Status: Recruiting
Phase of Trial: Phase III

Latest Information Update: 02 Jun 2020

At a glance

  • Drugs Sarilumab (Primary)
  • Indications COVID 2019 infections; Pneumonia
  • Focus Registrational; Therapeutic Use
  • Sponsors Sanofi
  • Most Recent Events

    • 14 May 2020 This trial has been suspended in Germany as per European Clinical Trials Database record.
    • 09 May 2020 Phase changed from phase II/III to Phase III. Number of patients changed to 400. Arms, outcome measures and eligibility criteria amended.
    • 06 May 2020 Planned End Date changed from 1 Jun 2021 to 1 Aug 2020.

Trial Overview

Purpose

Primary Objective: To evaluate the clinical efficacy of sarilumab relative to the control arm in adult patients hospitalized with severe or critical 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 (NEWS2) - 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 patients requiring rescue medication during the 28-day period - Evaluate need for admission into intensive care unit (ICU) - Evaluate duration of hospitalization (days) - The secondary safety objectives of the study are to evaluate the safety of sarilumab through hospitalization (up to day 29 if patient is still hospitalized) compared to the control arm as assessed by incidence of: - Serious adverse events (SAEs) - Major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia - Grade ≥2 infusion related reactions - Grade ≥2 hypersensitivity reactions - Increase in alanine transaminase (ALT) ≥3X upper limit of normal (ULN) (for patients with normal baseline) or >3X ULN AND at least 2-fold increase from baseline value (for patients with abnormal baseline) - Major or opportunistic bacterial or fungal infections

Primary Endpoints

Time to improvement of 2 points in clinical status assessment from baseline using the 7-point ordinal scale

description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
time_frame: Baseline to Day 29

Other Endpoints

Percent of patients alive at Day 29

time_frame: Day 29

Proportion of patients with one point improvement from baseline in clinical status assessment at days 4, 7, 15, 21, 29 using the 7-point ordinal scale

description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
time_frame: Baseline to Days 4, 7, 15, 21, 29

Mean change in the 7-point ordinal scale from baseline to Days 4, 7, 15, 21, and 29 (or until discharge)

description: The ordinal scale is an assessment of the clinical status. Score ranges 1-7. Lower score is worse.
time_frame: Baseline to Days 4, 7, 15, 21, 29 (or until discharge)

Time to resolution of fever

description: Defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner.
time_frame: Baseline to Day 29

Time to resolution of fever and improvement in oxygenation

description: Resolution of both fever and improvement in oxygenation. Resolution of fever is defined as body temperature (≤36.6°C [axilla], or ≤37.2 °C [oral], or ≤37.8°C [rectal or tympanic]) for at least 48 hours without antipyretics or until discharge, whichever is sooner. Improvement in oxygenation is defined as SpO2/FiO2 of 50 or greater compared to the nadir SpO2/FiO2 for at least 48 hours, or until discharge, whichever is sooner.
time_frame: Baseline to Day 29

Days with fever

description: Fever is defined as >37.4°C (axilla), or >38.0 °C (oral), or >38.4°C (rectal or tympanic) based on maximum value observed during a 24-hour period.
time_frame: Baseline to Day 29

Time to change in NEWS2 from baseline

description: The National Early Warning Score (NEWS2) is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
time_frame: Baseline to Day 29

Time to NEWS2 of <2 and maintained for 24 hours

description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
time_frame: Baseline to Day 29

Mean change from baseline to days 4, 7, 15, 21, and 29 in NEWS2

description: The NEWS2 is used to standardize the assessment of acute-illness severity, track the clinical condition of patients, and to alert clinical teams to patient deterioration. Score ranges from 0-20. A higher score is worse.
time_frame: Baseline to days 4, 7, 15, 21, and 29

Time-to-improvement in oxygenation

description: SpO2/FiO2 of 50 or greater compared to the nadir for at least 48 hours, or until discharge, whichever is sooner. SpO2 is oxygen saturation and FiO2 is the fraction of inspired oxygen.
time_frame: Baseline to Day 29

Alive off supplemental oxygen at day 29

description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
time_frame: Day 29

Days of hypoxemia

description: Hypoxemia is defined as SpO2 <93% on room air, or requiring supplemental oxygen, or mechanical ventilatory support.
time_frame: Baseline to Day 29

Days of supplemental oxygen use

description: Supplemental oxygen is defined as oxygen administration by nasal cannula, simple face mask, or other similar oxygen delivery device.
time_frame: Baseline to Day 29

Days of resting respiratory rate >24 breaths/min

time_frame: Baseline to Day 29

Time to saturation ≥94% on room air

time_frame: Baseline to Day 29

Ventilator free days in the first 28 days (to day 29)

time_frame: Baseline to Day 29

The number of patients with Initiation of mechanical ventilation, non-invasive ventilation, or use of high flow nasal cannula

description: For those not requiring these interventions at baseline.
time_frame: Baseline to Day 60

Proportion of patients requiring rescue medication during the 28-day period

time_frame: Baseline to Day 28

The number of patients transferred to the ICU or the need to transfer to the ICU (if the ICU is not available)

description: For patients are not in ICU at baseline
time_frame: Baseline to Day 60

Days of hospitalization among survivors

time_frame: Baseline to Day 60

Incidence of serious adverse events

time_frame: Baseline to Day 60

The incidence of major or opportunistic bacterial or fungal infections

time_frame: Baseline to Day 60

The incidence of major or opportunistic bacterial or fungal infections in patients with grade 4 neutropenia

time_frame: Baseline to Day 60

The incidence of hypersensitivity reactions, infusion reactions, gastrointestinal perforation

time_frame: Baseline to Day 60

The number of patients with clinically significant laboratory abnormalities

time_frame: Baseline to Day 60 [1]

Diseases Treated

Indication Qualifiers Patient Segments
COVID 2019 infections treatment -
Pneumonia treatment severe

Subjects

  • Subject Type patients
  • Number

    Planned: 460

  • Sex male & female
  • Age Group ≥ 18 years; adult; elderly

Patient Inclusion 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 SARS-CoV-2 infection

Patient Exclusion Criteria

Unlikely to survive after 48 hours from screening or unlikely to remain at the investigational site beyond 48 hours. Patients with multi organ dysfunction or requiring extracorporeal life support or renal replacement therapy are excluded. Presence of neutropenia less than 2000/mmˆ3, aspartate aminotransferase (AST) or ALT greater than 5 X ULN, platelets less than 50,000/mmˆ3 Prior immunosuppressive therapies Use of chronic oral 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 is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial Details

Identifiers

Identifier Owner
NCT04327388 ClinicalTrials.gov: US National Institutes of Health
EudraCT2020-001162-12 European Clinical Trials Database
EFC16844 Sanofi
U1111-1249-6021 World Health Organisation

Organisations

  • Sponsors Sanofi
  • Affiliations Regeneron Pharmaceuticals; Sanofi

Trial Dates

  • Initiation Dates

    Planned : 29 Mar 2020

    Actual : 28 Mar 2020

  • Primary Completion Dates

    Planned : 01 Jul 2020

  • End Dates

    Planned : 01 Aug 2020

Other Details

  • Design double-blind; multicentre; parallel; prospective; randomised
  • Phase of Trial Phase III
  • Location Argentina; Canada; Chile; France; Germany; Israel; Italy; Japan; Russia; Spain
  • Focus Registrational; Therapeutic Use

Interventions

Drugs Route Formulation
SarilumabPrimary Drug Intravenous Infusion, Injection

Sarilumab Dose 1

Sarilumab Dose 1 given intravenously one time on Day 1. Patients may receive a second dose with Sarilumab Dose 1 24 to 48 hours after the first dose.
Drug: Sarilumab SAR153191 (Pharmaceutical form:Solution for injection Route of administration: Intravenous infusion) Other Name: REGN88

Sarilumab Dose 2

Sarilumab Dose 2 given intravenously one time on Day 1. Patients may receive a second dose with Sarilumab Dose 2 24 to 48 hours after the first dose.
Drug: Sarilumab SAR153191 (Pharmaceutical form:Solution for injection Route of administration: Intravenous infusion) Other Name: REGN88

Matching placebo

Matching placebo given intravenously one time on Day 1. Patients may receive a second dose with matching placebo 24 to 48 hours after the first dose.
Drug: Placebo (Pharmaceutical form:Solution for injection Route of administration: Intravenous infusion)

Trial Centres

Investigators

Investigator Centre Name Trial Centre Country
Clinical Sciences & Operations
Trial Transparency email recommended (Toll free number for US & Canada)
800-633-1610 Ext: option 6
Contact-US@sanofi.com
show details
Sanofi
-
CONTACT POINT
VIALE BODIO, 37/B,
MILANO, 20158, Italy
Tel:800226343
Fax:00290239394168
informazioni.medicoscientifiche@sanofi.com
show details
SANOFI S.P.A. Italy
Direction des Operations Cliniques
1 avenue Pierre Brossolette,
Chilly-Mazarin, 91385,
France.
Public-Registry-MA-France@sanofi.com
show details
Sanofi-aventis France France
Trial Transparency email recommended (Toll free number for US & Canada)
800-633-1610 Ext: option 6 Contact-US@sanofi.com
show details
-

Centres

Centre Name Location Trial Centre Country
-
-
-
- Ashdod Israel
- Barcelona Spain
- Bonn Germany
- Bordeaux Cedex France
- Braunschweig Germany
- Caba Argentina
- Clamart France
- Essen Germany
- Fuchu-Shi Japan
- Iruma-Gun Japan
- Jerusalem Israel
- Köln Germany
- Kamakura-Shi Japan
- La Roche Sur Yon Cedex 9 France
- Münster Germany
- Madrid Spain
- Milano Italy
- Modena Italy
- Montreal Canada
- Moscow Russia
- Nantes France
- Paris Cedex 18 France
- Parma Italy
- Ramat Gan Israel
- Rozzano Italy
- Santiago Chile
- Strasbourg France
- Suresnes France
- Talca Chile
- Toronto Canada
- Vancouver Canada
Regeneron Pharmaceuticals
-
-
Sanofi
-
-
SANOFI S.P.A. MILANO Italy
Sanofi-Aventis Deutschland GmbH
medinfo.de@sanofi.com
show details
-
Germany
Sanofi-aventis France Chilly-Mazarin France
Sanofi-aventis Recherche et Developpement
-
France

Trial History

Event Date Event Type Comment
02 Jun 2020 Other trial event Last checked against ClinicalTrials.gov record. Updated 02 Jun 2020
14 May 2020 Other trial event This trial has been suspended in Germany as per European Clinical Trials Database record. Updated 14 May 2020
14 May 2020 Other trial event Last checked against European Clinical Trials Database record. Updated 14 May 2020
09 May 2020 Protocol amendment Phase changed from phase II/III to Phase III. Number of patients changed to 400. Arms, outcome measures and eligibility criteria amended. Updated 13 May 2020
06 May 2020 Completion date Planned End Date changed from 1 Jun 2021 to 1 Aug 2020. Updated 08 May 2020
27 Apr 2020 Other trial event According to a Sanofi media release, amendments similar to US Phase II/III trial will be considered for this trial. Updated 05 May 2020
27 Apr 2020 Other trial event According to a Regeneron Pharmaceuticals media release, initial results from this trial are expected in the third quarter of 2020. Updated 29 Apr 2020
07 Apr 2020 Other trial event Planned initiation date changed from 28 Mar 2020 to 29 Mar 2020. Updated 13 Apr 2020
02 Apr 2020 Other trial event New source identified and integrated (ClinicalTrials.gov: US National Institutes of Health;NCT04327388 ) Updated 02 Apr 2020
01 Apr 2020 Status change - recruiting Status changed from not yet recruiting to recruiting. Updated 03 Apr 2020
30 Mar 2020 Other trial event According to a Sanofi media release, both the companies (Sanofi and Regeneron Pharmaceuticals) are continuing to work with health authorities around the world to secure initiation at additional sites. Updated 31 Mar 2020
30 Mar 2020 Other trial event According to a Sanofi media release, the first patient outside of the U.S. has been treated in this trial, as part of a global clinical program evaluating Kevzara (sarilumab) in patients hospitalized with severe COVID-19. Updated 31 Mar 2020
27 Mar 2020 Other trial event New Source identified and integrated(European Clinical Trials Database:EudraCT2020-001162-12) Updated 27 Mar 2020
25 Mar 2020 Status change - recruiting Status changed from planning to recruiting. Updated 27 Mar 2020
20 Mar 2020 New trial record New trial record Updated 20 Mar 2020
16 Mar 2020 Other trial event According to a Regeneron Pharmaceuticals media release, Sanofi expect to rapidly initiate trials outside the U.S. in the coming weeks, including areas most affected by the pandemic such as Italy. Updated 20 Mar 2020
16 Mar 2020 Other trial event According to a Regeneron Pharmaceuticals media release, Regeneron Pharmaceuticals and Sanofi have started a clinical program evaluating Kevzara (sarilumab) in patients hospitalized with severe COVID-19 infection.Regeneron is leading U.S. trials, Sanofi will lead this upcoming ex-U.S. trial. Updated 20 Mar 2020

References

  1. ClinicalTrials.gov: US National Institutes of Health. Trial-Reg 2016;.

    Available from: URL: http://clinicaltrials.gov
  2. Regeneron Pharmaceuticals, Sanofi. Regeneron and Sanofi Provide Update on U.S. Phase 2/3 Adaptive-Designed Trial of Kevzara(Rm) (sarilumab) in Hospitalized COVID-19 Patients. Media-Rel 2020;.

    Media Release
  3. European Clinical Trials Database. Trial-Reg 2016;.

    Available from: URL: https://www.clinicaltrialsregister.eu
  4. Sanofi. Sanofi and Regeneron provide update on U.S. Phase 2/3 adaptive-designed trial in hospitalized COVID-19 patients. Media-Rel 2020;.

    Media Release
  5. Regeneron Pharmaceuticals, Sanofi. Regeneron and Sanofi Begin Global Kevzara(R) (sarilumab) Clinical Trial Program in Patients with Severe COVID-19. Media-Rel 2020;.

    Media Release
  6. Regeneron Pharmaceuticals. First patient outside U.S. treated in global Kevzara(Rm) (sarilumab) clinical trial program for patients with severe COVID-19. Media-Rel 2020;.

    Media Release
  7. Sanofi. Sanofi: First patient outside U.S. treated in global Kevzara(Rm) (sarilumab) clinical trial program for patients with severe COVID-19. Media-Rel 2020;.

    Media Release
Back to top