Clinical trial NCT04327388: Sarilumab COVID-19
Official title: An Adaptive Phase 3, Randomized, Double-blind, Placebo-controlled Study Assessing Efficacy and Safety of Sarilumab for Hospitalized Patients With COVID19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Corona Virus Infection
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
Collaborators: name: Regeneron Pharmaceuticals
First posted: 2020-03-31
Enrollment: 420
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility 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.

Primary outcomes:
measure: Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points
timeFrame: Baseline to Day 29
Secondary outcomes:
measure: Percentage of Participants Who Were Alive at Day 29
timeFrame: Day 29
measure: 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
timeFrame: Baseline, Days 4, 7, 15, 21, and 29
measure: Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score
timeFrame: Baseline, Days 4, 7, 15, 21, and 29
measure: Time to Resolution of Fever
timeFrame: Baseline to Day 29
measure: Time to Resolution of Fever and Improvement in Oxygenation
timeFrame: Baseline to Day 29
measure: Number of Days With Fever
timeFrame: Baseline to Day 29
measure: Percentage of Participants in Each National Early Warning Score 2 (NEWS2) Clinical Risk Category at Baseline and at Days 4, 7, 15, 21, and 29
timeFrame: Baseline, Days 4, 7, 15, 21, and 29
measure: Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours
timeFrame: Baseline to Day 29
measure: Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2
timeFrame: Baseline, Days 4, 7, 15, 21, and 29
measure: Time-to-improvement in Oxygenation
timeFrame: Baseline to Day 29
measure: Percentage of Participants Alive Off Supplemental Oxygen at Day 29
timeFrame: Day 29
measure: Percentage of Days With Hypoxemia
timeFrame: Baseline to Day 29
measure: Percentage of Days With Supplemental Oxygen Use
timeFrame: Baseline to Day 29
measure: Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute
timeFrame: Baseline to Day 29
measure: Time to Oxygen Saturation >= 94% on Room Air
timeFrame: Baseline to Day 29
measure: Mean Number of Ventilator Free Days
timeFrame: Baseline to Day 29
measure: Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula
timeFrame: Baseline to Day 29
measure: Percentage of Participants Who Required Rescue Medication
timeFrame: Baseline to Day 28
measure: Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study
timeFrame: Baseline to Day 29
measure: Number of Days of Hospitalization Among Survivors (Alive Participants)
timeFrame: At Day 60
measure: Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
timeFrame: Baseline up to 60 days
measure: Number of Participants With Major or Opportunistic Bacterial or Fungal Infections
timeFrame: Baseline up to 60 days
measure: Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection
timeFrame: Baseline up to 60 days
measure: Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation
timeFrame: Baseline up to 60 days
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets
timeFrame: Baseline up to 60 days
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters
timeFrame: Baseline up to 60 days
measure: Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters
timeFrame: Baseline up to 60 days
Other outcomes:
Locations:
city: Caba
country: Argentina
facility: Investigational Site Number 0320001
city: Caba
country: Argentina
facility: Investigational Site Number 0320003
city: Caba
country: Argentina
facility: Investigational Site Number 0320004
city: Porto Alegre
country: Brazil
facility: Investigational Site Number 0760003
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760001
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 0760002
city: São José Do Rio Preto
country: Brazil
facility: Investigational Site Number 0760004
city: São Paulo
country: Brazil
facility: Investigational Site Number 0760005
city: Montreal
country: Canada
facility: Investigational Site Number 1240001
city: Montreal
country: Canada
facility: Investigational Site Number 1240005
city: Toronto
country: Canada
facility: Investigational Site Number 1240004
city: Toronto
country: Canada
facility: Investigational Site Number 1240002
city: Vancouver
country: Canada
facility: Investigational Site Number 1240003
city: Santiago
country: Chile
facility: Investigational Site Number 1520003
city: Santiago
country: Chile
facility: Investigational Site Number 1520002
city: Santiago
country: Chile
facility: Investigational Site Number 1520004
city: Talca
country: Chile
facility: Investigational Site Number 1520001
city: Bordeaux Cedex
country: France
facility: Investigational Site Number 2500001
city: Clamart
country: France
facility: Investigational Site Number 2500007
city: La Roche Sur Yon Cedex 9
country: France
facility: Investigational Site Number 2500006
city: Nantes
country: France
facility: Investigational Site Number 2500002
city: Paris Cedex 18
country: France
facility: Investigational Site Number 2500005
city: Strasbourg
country: France
facility: Investigational Site Number 2500003
city: Suresnes
country: France
facility: Investigational Site Number 2500004
city: Essen
country: Germany
facility: Investigational Site Number 2760002
city: Köln
country: Germany
facility: Investigational Site Number 2760004
city: Münster
country: Germany
facility: Investigational Site Number 2760001
city: Ashdod
country: Israel
facility: Investigational site number 3760003
city: Jerusalem
country: Israel
facility: Investigational Site Number 3760002
city: Ramat Gan
country: Israel
facility: Investigational Site Number 3760001
city: Milano
country: Italy
facility: Investigational Site Number 3800005
city: Milano
country: Italy
facility: Investigational Site Number 3800001
city: Milano
country: Italy
facility: Investigational Site Number 3800002
city: Modena
country: Italy
facility: Investigational Site Number 3800003
city: Parma
country: Italy
facility: Investigational Site Number 3800004
city: Rozzano
country: Italy
facility: Investigational Site Number 3800006
city: Fuchu-Shi
country: Japan
facility: Investigational Site Number 3920002
city: Iruma-Gun
country: Japan
facility: Investigational Site Number 3920003
city: Kamakura-Shi
country: Japan
facility: Investigational Site Number 3920001
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430003
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430002
city: Moscow
country: Russian Federation
facility: Investigational Site Number 6430001
city: Barcelona
country: Spain
facility: Investigational Site Number 7240003
city: Barcelona
country: Spain
facility: Investigational Site Number 7240004
city: Madrid
country: Spain
facility: Investigational Site Number 7240002
city: Madrid
country: Spain
facility: Investigational Site Number 7240005
city: Madrid
country: Spain
facility: Investigational Site Number 7240001
Study officials:
affiliation: Sanofi
name: Clinical Sciences & Operations
role: STUDY_DIRECTOR
References:
citation: 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.