Back to resultsStudy to Evaluate the Safety and Efficacy of ATYR1923 (Efzofitimod) In Participants With Severe Pneumonia Related to COVID-19
Primary Purpose
SARS-CoV-2 (COVID-19) Severe Pneumonia
Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Efzofitimod 1 mg/kg
Efzofitimod 3 mg/kg
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for SARS-CoV-2 (COVID-19) Severe Pneumonia focused on measuring SARS-CoV-2, CoV-2, ATYR1923 (efzofitimod), acute respiratory distress syndrome, ARDS, SARS-CoV-2 Infection, COVID-19, Severe Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Confirmation of SARS-CoV2 infection by PCR.
Severe pneumonia related to SARS-CoV2 infection, defined as fever or suspected respiratory infection with radiographic abnormalities suggestive of viral pneumonia, plus at least one of the following:
- Respiratory rate >30 breaths/min; or
- Severe respiratory distress, as determined by the Investigator; or;
- Oxygen saturation (SpO2) ≤93% on room air.
Exclusion Criteria:
- Patient is intubated/mechanically ventilated.
- In the opinion of the Investigator, patient's progression to death is imminent.
- Treatment with immunosuppressant/immunotherapy drugs, including but not limited to IL-6 inhibitors, 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.
Sites / Locations
- University of Alabama at Birmingham
- aTyr Investigative Site
- University of Miami
- University of Iowa
- Anne Arundel Medical Center
- aTyr Investigative Site
- aTyr Investigative Site
- Inova Fairfax Medical Campus
- Alliance Medical Service, Cardio Pulmonary Research
- Manati Medical Center
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Placebo Comparator
Arm Label
Efzofitimod 1 mg/kg
Efzofitimod 3 mg/kg
Placebo
Arm Description
Participants will receive single dose of efzofitimod 1 milligrams/kilograms (mg/kg) IV infusion on Day 1.
Participants will receive single dose of efzofitimod 3 mg/kg IV infusion on Day 1.
Participants will receive placebo matched to efzofitimod IV infusion on Day 1.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04412668
Brief Title
Study to Evaluate the Safety and Efficacy of ATYR1923 (Efzofitimod) In Participants With Severe Pneumonia Related to COVID-19
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)
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Completed
Study Start Date
June 4, 2020 (Actual)
Primary Completion Date
October 23, 2020 (Actual)
Study Completion Date
October 23, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
aTyr Pharma, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2 (COVID-19) Severe Pneumonia
Keywords
SARS-CoV-2, CoV-2, ATYR1923 (efzofitimod), acute respiratory distress syndrome, ARDS, SARS-CoV-2 Infection, COVID-19, Severe Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
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
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
The Investigator, Sponsor, and participant will be blinded to treatment assignment; study center pharmacy personnel will be unblinded.
Allocation
Randomized
Enrollment
36 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Efzofitimod 1 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive single dose of efzofitimod 1 milligrams/kilograms (mg/kg) IV infusion on Day 1.
Arm Title
Efzofitimod 3 mg/kg
Arm Type
Experimental
Arm Description
Participants will receive single dose of efzofitimod 3 mg/kg IV infusion on Day 1.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Participants will receive placebo matched to efzofitimod IV infusion on Day 1.
Intervention Type
Drug
Intervention Name(s)
Efzofitimod 1 mg/kg
Intervention Description
Concentrate for solution for infusion
Intervention Type
Drug
Intervention Name(s)
Efzofitimod 3 mg/kg
Intervention Description
Concentrate for solution for infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Concentrate for solution for infusion
Primary Outcome Measure Information:
Title
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description
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.
Time Frame
Baseline up to Day 60
Secondary Outcome Measure Information:
Title
Time to Hospital Discharge
Description
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.
Time Frame
Baseline up to Day 60
Title
Time to Recovery (World Health Organization [WHO] Ordinal Scale Score ≤3)
Description
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.
Time Frame
Baseline up to Day 60
Title
Number of Participants Who Achieved Recovery (WHO Ordinal Scale Score ≤3) by Day 14 and Day 28
Description
The number of participants was the non-missing value at the visit, which was used as the denominator for percentage calculation.
Time Frame
Baseline through Day 14 and Day 28
Title
Number of Days With Supplemental Oxygen (O2)
Description
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.
Time Frame
Baseline up to Day 60
Title
Number of Days With Fever (Temperature >100.4ºF [38.0ºC])
Description
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.
Time Frame
Baseline up to Day 14
Title
Number of Participants With a Change From Baseline in World Health Organization (WHO) Ordinal Scale Score on Day 60
Description
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.
Time Frame
Baseline, Day 60
Title
Time to Improvement From Inpatient Hospital Admission Based on at Least a 1-Point Reduction in WHO Ordinal Scale Score
Description
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.
Time Frame
Baseline up to Day 60
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Facility Information:
Facility Name
University of Alabama at Birmingham
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35294
Country
United States
Facility Name
aTyr Investigative Site
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33125
Country
United States
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Facility Name
Anne Arundel Medical Center
City
Annapolis
State/Province
Maryland
ZIP/Postal Code
21401
Country
United States
Facility Name
aTyr Investigative Site
City
Vineland
State/Province
New Jersey
ZIP/Postal Code
08360
Country
United States
Facility Name
aTyr Investigative Site
City
Toledo
State/Province
Ohio
ZIP/Postal Code
43614
Country
United States
Facility Name
Inova Fairfax Medical Campus
City
Falls Church
State/Province
Virginia
ZIP/Postal Code
22042
Country
United States
Facility Name
Alliance Medical Service, Cardio Pulmonary Research
City
Guaynabo
ZIP/Postal Code
00968
Country
Puerto Rico
Facility Name
Manati Medical Center
City
Manatí
ZIP/Postal Code
00674
Country
Puerto Rico
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the Safety and Efficacy of ATYR1923 (Efzofitimod) In Participants With Severe Pneumonia Related to COVID-19
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