Study to Evaluate the Safety and Efficacy of ATYR1923 (Efzofitimod) In Participants With Severe Pneumonia Related to COVID-19

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and preliminary efficacy of efzofitimod, compared to placebo matched to efzofitimod, in hospitalized participants with SARS-CoV-2 (COVID-19) severe pneumonia not requiring mechanical ventilation.

Official Title
-----------------
A Randomized Double-Blind Placebo-Controlled Study to Evaluate the Safety and Efficacy of ATYR1923 In Adult Patients With Severe Pneumonia Related to SARS-CoV-2 Infection (COVID-19)

Conditions
-----------------
SARS-CoV-2 (COVID-19) Severe Pneumonia

Intervention / Treatment
-----------------
* Drug: Efzofitimod 1 mg/kg
* Drug: Efzofitimod 3 mg/kg
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmation of SARS-CoV-2 infection by polymerase chain reaction (PCR). Severe pneumonia related to SARS-CoV-2 infection, defined as fever or suspected respiratory infection with radiographic abnormalities suggestive of viral pneumonia, plus at least 1 of the following: Respiratory rate >30 breaths/minute; Severe respiratory distress, as determined by the Investigator; Oxygen saturation (SpO2) ≤93% on room air. Exclusion Criteria: Participant is intubated/mechanically ventilated. In the opinion of the Investigator, participant's progression to death is imminent. Treatment with immunosuppressant/immunotherapy drugs, including but not limited to interleukin (IL)-6 inhibitors, tumor necrosis factor-alpha (TNF-α) inhibitors, anti-IL-1 agents and janus kinase inhibitors within 5 half-lives or 30 days prior to Day 1. Use of chronic (>30 days) oral corticosteroids for a non-COVID-19-related condition in a dose higher than prednisone 10 mg or equivalent per day. Weight >165 kg or <40 kg.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Participants will be randomized 1:1:1 to a single intravenous (IV) dose of efzofitimod 1 mg/kg, efzofitimod 3 mg/kg, or placebo matched to efzofitimod.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Efzofitimod 1 mg/kg<br>Participants will receive single dose of efzofitimod 1 milligrams/kilograms (mg/kg) IV infusion on Day 1. | Drug: Efzofitimod 1 mg/kg<br>* Concentrate for solution for infusion<br>|
| Experimental: Efzofitimod 3 mg/kg<br>Participants will receive single dose of efzofitimod 3 mg/kg IV infusion on Day 1. | Drug: Efzofitimod 3 mg/kg<br>* Concentrate for solution for infusion<br>|
| Placebo Comparator: Placebo<br>Participants will receive placebo matched to efzofitimod IV infusion on Day 1. | Drug: Placebo<br>* Concentrate for solution for infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) | TEAEs were defined as adverse events (AEs) with an onset following administration of the first dose of study drug. AEs were defined as any untoward medical occurrence in a participant administered study drug and that does not necessarily have a causal relationship with the study drug. Worsening of a pre-existing medical condition should have been considered an AE if there was either an increase in severity, frequency, or duration of the condition or an association with significantly worse outcomes. SAEs were defined as any AE that, in the view of either the Investigator or Sponsor, resulted in any of the following outcomes as fatal, life-threatening, required in-participant hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, a congenital anomaly/birth defect, an important medical event. A summary of all SAEs and Other AEs (nonserious) regardless of causality is located in 'Reported Adverse Events' Section. | Baseline up to Day 60 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Hospital Discharge | Time to hospital discharge was based on Kaplan-Meier estimate and was calculated as: discharge date - study drug administration date. Participants who died during hospitalization were censored at death date. Participants who remained hospitalized at end of study (EOS) were censored at EOS visit. | Baseline up to Day 60 | 
| Time to Recovery (World Health Organization [WHO] Ordinal Scale Score ≤3) | Time to recovery was based on Kaplan-Meier estimate and was calculated as: date of first time with a WHO scale score ≤3 - study drug administration date or date of discharge from hospital - study drug administration date, whichever occurred first. In the case that a participant did not reach WHO scale score ≤3 criteria, the participant was censored at EOS visit. | Baseline up to Day 60 | 
| Number of Participants Who Achieved Recovery (WHO Ordinal Scale Score ≤3) by Day 14 and Day 28 | The number of participants was the non-missing value at the visit, which was used as the denominator for percentage calculation. | Baseline through Day 14 and Day 28 | 
| Number of Days With Supplemental Oxygen (O2) | Number of days with supplemental O2 was calculated as stop date of supplemental O2 - start date of supplemental oxygen +1, if supplemental O2 started after study drug administration; otherwise, number of days with supplemental O2 was calculated as stop date of supplemental O2 - date of study drug administration +1. If there were multiple periods of supplemental O2, total days were the sum of each period. | Baseline up to Day 60 | 
| Number of Days With Fever (Temperature >100.4ºF [38.0ºC]) | Number of days with fever was calculated as stop date of fever - start date of fever +1, if fever started after study drug administration; otherwise, number of days with fever was calculated as stop date of fever - date of study drug administration +1. If there were multiple periods of fever, total days was the sum of each period. | Baseline up to Day 14 | 
| Number of Participants With a Change From Baseline in World Health Organization (WHO) Ordinal Scale Score on Day 60 | WHO ordinal scale rated the clinical improvement of the participants on a scale of 0-8, where 0=No clinical or virological evidence of infection, 1=No limitation of activities, 2=limitation of activities, 3=Hospitalized, no oxygen therapy, 4=Oxygen by mask or nasal prongs, 5=Non-invasive ventilation or high flow oxygen, 6=Intubation and mechanical ventilation, 7=Ventilation + additional organ support, 8=Death. Change from Baseline data were represented on a scale of -7 to 4, where -7=a better change from Baseline score and 4=a worse change from Baseline score. Change from Baseline was derived as: visit value - Baseline value. | Baseline, Day 60 | 
| Time to Improvement From Inpatient Hospital Admission Based on at Least a 1-Point Reduction in WHO Ordinal Scale Score | Time to improvement was based on Kaplan-Meier estimate and was defined as the date of decrease in WHO scale compared to Baseline by at least 1 point - study drug administration date or date of discharge from hospital - study drug administration date, whichever occurred first. In the case that a participant did not reach an improvement, the participant was censored at end of study date. | Baseline up to Day 60 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SARS-CoV-2, CoV-2, ATYR1923 (efzofitimod), acute respiratory distress syndrome, ARDS, SARS-CoV-2 Infection, COVID-19, Severe Pneumonia