Phase 3
N=420
Sarilumab COVID-19
Corona Virus Infection
Bottom Line
View on ClinicalTrials.gov: NCT04327388 ↗Enrolled (actual)
420
Serious AEs
27.2%
Results posted
May 2021
Primary outcome: Primary: Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points — 10.0; 10.0; 12.0 days — p=0.9561
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Sarilumab SAR153191 (Drug); Placebo (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Sanofi
- Primary completion
- Jul 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Time to Improvement in Clinical Status of Participants (Using 7-point Ordinal Scale Score) by at Least 2 Points |
10.0; 10.0; 12.0 | 0.9561 |
| SECONDARY Percentage of Participants Who Were Alive at Day 29 |
89.9; 91.9; 91.7 | 0.6280 |
| SECONDARY 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 |
25.2; 25.4; 23.8; 51.6; 48.6; 42.9 | — |
| SECONDARY Change From Baseline at Days 4, 7, 15, 21, 29 in 7-point Ordinal Scale Score |
0.1; 0.1; 0.2; 0.7; 0.7; 0.7 | — |
| SECONDARY Time to Resolution of Fever |
8.0; 9.0; 7.0 | — |
| SECONDARY Time to Resolution of Fever and Improvement in Oxygenation |
9.0; 10.0; 8.0 | — |
| SECONDARY Number of Days With Fever |
1.2; 1.3; 1.8 | — |
| SECONDARY 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 |
28.8; 22.1; 34.2; 0; 0; 0 | — |
| SECONDARY Time to National Early Warning Score of Less Than (<) 2 and Maintained for 24 Hours |
9.0; 9.0; 11.0 | — |
| SECONDARY Change From Baseline at Days 4, 7, 15, 21, and 29 in National Early Warning Score 2 |
-1.07; -1.25; -0.36; -1.63; -1.47; -0.83 | — |
| SECONDARY Time-to-improvement in Oxygenation |
6.0; 6.0; 7.0 | — |
| SECONDARY Percentage of Participants Alive Off Supplemental Oxygen at Day 29 |
84.9; 83.8; 86.9 | — |
| SECONDARY Percentage of Days With Hypoxemia |
73.01; 75.10; 76.32 | — |
| SECONDARY Percentage of Days With Supplemental Oxygen Use |
70.57; 73.30; 73.23 | — |
| SECONDARY Percentage of Days With Resting Respiratory Rate > 24 Breaths Per Minute |
14.74; 14.58; 15.74 | — |
| SECONDARY Time to Oxygen Saturation >= 94% on Room Air |
8.0; 8.0; 8.0 | — |
| SECONDARY Mean Number of Ventilator Free Days |
23.8; 24.0; 24.9 | — |
| SECONDARY Percentage of Participants With Initiation of Mechanical Ventilation, Non-invasive Ventilation, or Use of High Flow Nasal Cannula |
20.5; 23.4; 19.1 | — |
| SECONDARY Percentage of Participants Who Required Rescue Medication |
13.8; 15.0; 22.6 | — |
| SECONDARY Percentage of Participants Who Needed Intensive Care Unit (ICU) Care During Study |
11.2; 14.9; 12.5 | — |
| SECONDARY Number of Days of Hospitalization Among Survivors (Alive Participants) |
15.6; 16.1; 15.9 | — |
| SECONDARY Number of Participants With Treatment-emergent Serious Adverse Events (SAEs) |
42; 51; 20 | — |
| SECONDARY Number of Participants With Major or Opportunistic Bacterial or Fungal Infections |
8; 15; 3 | — |
| SECONDARY Number of Participants With Grade 4 Neutropenia and Grade 4 Neutropenia With Concurrent Invasive Infection |
3; 6; 0; 0; 0 | — |
| SECONDARY Number of Participants With Grade >=2 Infusion Reactions, Grade >=2 Hypersensitivity Reactions and Gastrointestinal Perforation |
1; 6; 0; 1; 7; 0 | — |
| SECONDARY Number of Participants With Potentially Clinically Significant Laboratory Abnormalities (PCSA): Hematological Parameter - Hemoglobin, Leukocytes and Platelets |
29; 34; 15; 0; 0; 0 | — |
| SECONDARY Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Renal Function Parameters |
15; 15; 5; 31; 30; 10 | — |
| SECONDARY Number of Participants With Potentially Clinically Significant Laboratory Abnormalities: Liver Function Parameters |
60; 63; 24; 28; 25; 12 | — |
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.
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.
Data sourced from ClinicalTrials.gov (NCT04327388). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.