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COVID-19 morbidity and mortality has been associated with Cytokine Release Syndrome (CRS) and Acute Respiratory Distress Syndrome (ARDS).
ATI-450 is an oral small molecule MAPKAPK2 (MK2) inhibitor that potently inhibits multiple inflammatory cytokines.
The investigator hypothesizes that MK2 pathway blockade during active COVID-19 infection in hospitalized participants will result in improvement in respiratory-failure free survival.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| ATI-450 | Active Comparator | Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days |
|
| Placebo | Placebo Comparator | Treated with matched placebo, orally, twice daily for 14 days |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| ATI-450 | Drug | 50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently. |
| Measure | Description | Time Frame |
|---|---|---|
| Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450 | Proportion of responders on Day 14 defined as all subjects who are alive, free of respiratory failure (do not require supplemental oxygen) and do not experience negative intercurrent events by Day 14 of the trial will be considered responders, as assessed by participant medical records. | Study day 14 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in 7 Point-ordinal Scale | Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Participants were assessed on a 7-point categorical scale, and change in scores between timepoints is reported. This scale measures illness severity over time and has a range of 0-7.
|
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Gregory Gan, MD, PhD | The University of Kansas | Principal Investigator |
| Deepika Polineni, MD, PhD | The University of Kansas | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| The University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | ATI-450 | Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days ATI-450: 50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently. |
| FG001 | Placebo | Treated with matched placebo, orally, twice daily for 14 days Placebo: Placebo pill will be taken twice daily preferably spaced 12 hours apart. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | ATI-450 | Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days ATI-450: 50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450 | Proportion of responders on Day 14 defined as all subjects who are alive, free of respiratory failure (do not require supplemental oxygen) and do not experience negative intercurrent events by Day 14 of the trial will be considered responders, as assessed by participant medical records. | Posted | Number | 90% Confidence Interval | percentage of total patients | Study day 14 |
|
Adverse events were collected from initiation of study treatment and continues until the Day 60 safety follow-up.
Per protocol, medical history adverse events are recorded and graded using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Serious adverse event and adverse event monitoring begins after initiation of study treatment and continues until the Day 60 safety follow-up. This Day 60 follow-up check and will be done by phone.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | ATI-450 | Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days ATI-450: 50 mg (as determined from Phase I study) per dose. (100 mg per day). Up to a maximum of 14 days while inpatient. Patients discharged home or transferred to the intensive care unit (ICU) will be discontinued off drug permanently. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| multi-organ failure | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| superficial thrombophlebitis | Vascular disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Gregory Gan, MD PhD | University of Kansas Medical Center | 913 588 5881 | ggan@kumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Mar 27, 2023 | Mar 7, 2025 | Prot_002.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Mar 27, 2023 | Mar 7, 2025 | SAP_003.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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| Placebo | Drug | Placebo pill will be taken twice daily preferably spaced 12 hours apart. |
|
| Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months |
| Number of Participants With a Need for Advanced Respiratory Care | Derived from medical record | Baseline and continuous throughout hospitalization up to 14 days |
| All-cause Mortality | Noted in participant medical record | Baseline and through day 60 |
| Treatment-emergent Adverse Events | Number of adverse events (AEs), as assessed by CTCAE v5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (Activities of Daily Living). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Up to Day 60 |
| Treatment-emergent Serious Adverse Events | Number of serious adverse events (SAEs), as assessed by CTCAE v5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Up to Day 60 |
| Number of Participants With Normalization of Fever for 24 Hours | Standard daily temperature measurement and obtained from participant medical record | Baseline through day 14 or at discharge <day 14 |
| Number of Participants Who Develop New Bacterial Infection | Noted in participant medical record | Continuous throughout hospitalization up to 14 days |
| Number of Participants Who Develop New Fungal Infection | Noted in participant medical record | Continuous throughout hospitalization up to 14 days |
| Number of Adult Respiratory Distress Syndrome (ARDS2) | Noted in participant medical record | From day 1 though day 14 or at discharge <day 14 |
| Change in Serum Cytokine Interleukin (IL)-6 | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | Baseline to End of Treatment, or Day 14 |
| Change in Serum Cytokine IL-8 | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | Baseline to End of Treatment, or Day 14 |
| Change in Serum Cytokines IL-1β | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | Baseline to End of Treatment, or Day 14 |
| Change in Serum Cytokine Tumor Necrosis Factor (TNF-α) | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | Baseline to End of Treatment, or Day 14 |
| Placebo |
Treated with matched placebo, orally, twice daily for 14 days Placebo: Placebo pill will be taken twice daily preferably spaced 12 hours apart. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Median | Full Range | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Placebo |
Treated with matched placebo, orally, twice daily for 14 days Placebo: Placebo pill will be taken twice daily preferably spaced 12 hours apart. |
|
|
| Secondary | Change in 7 Point-ordinal Scale | Using World Health Organization (WHO) COVID-19 Ordinal scale measuring: Participants were assessed on a 7-point categorical scale, and change in scores between timepoints is reported. This scale measures illness severity over time and has a range of 0-7.
| Posted | Mean | Standard Deviation | score on a scale | Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months |
|
|
|
| Secondary | Number of Participants With a Need for Advanced Respiratory Care | Derived from medical record | Posted | Count of Participants | Participants | Baseline and continuous throughout hospitalization up to 14 days |
|
|
|
| Secondary | All-cause Mortality | Noted in participant medical record | Posted | Number | participants | Baseline and through day 60 |
|
|
|
| Secondary | Treatment-emergent Adverse Events | Number of adverse events (AEs), as assessed by CTCAE v5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL (Activities of Daily Living). Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Posted | Number | adverse events | Up to Day 60 |
|
|
|
| Secondary | Treatment-emergent Serious Adverse Events | Number of serious adverse events (SAEs), as assessed by CTCAE v5.0. Grade refers to the severity of the AE. The CTCAE displays Grades 1 through 5 with unique clinical descriptions of severity for each AE based on this general guideline: Grade 1 Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2 Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL. Grade 3 Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self care ADL. Grade 4 Life-threatening consequences; urgent intervention indicated. Grade 5 Death related to AE. | Report of any treatment-emergent Serious adverse events (TeSAE) | Posted | Number | serious adverse events | Up to Day 60 |
|
|
|
| Secondary | Number of Participants With Normalization of Fever for 24 Hours | Standard daily temperature measurement and obtained from participant medical record | Posted | Number | participants | Baseline through day 14 or at discharge <day 14 |
|
|
|
| Secondary | Number of Participants Who Develop New Bacterial Infection | Noted in participant medical record | Posted | Number | participants | Continuous throughout hospitalization up to 14 days |
|
|
|
| Secondary | Number of Participants Who Develop New Fungal Infection | Noted in participant medical record | Posted | Number | participants | Continuous throughout hospitalization up to 14 days |
|
|
|
| Secondary | Number of Adult Respiratory Distress Syndrome (ARDS2) | Noted in participant medical record | Posted | Count of Participants | Participants | From day 1 though day 14 or at discharge <day 14 |
|
|
|
| Secondary | Change in Serum Cytokine Interleukin (IL)-6 | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | baseline vs EoT | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline to End of Treatment, or Day 14 |
|
|
|
| Secondary | Change in Serum Cytokine IL-8 | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | baseline vs EoT | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline to End of Treatment, or Day 14 |
|
|
|
| Secondary | Change in Serum Cytokines IL-1β | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | Baseline vs EoT - this could not be measured because analyte could not be detected | Posted | Mean | Standard Deviation | percentage of baseline | Baseline to End of Treatment, or Day 14 |
|
|
|
| Secondary | Change in Serum Cytokine Tumor Necrosis Factor (TNF-α) | Plasma was assayed by Confluence Discovery Technologies using the MesoScale Discovery Platform from biobanked samples stored from the University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core, expressed in pg/mL. Change in biomarker was reported as a percent based on (EOT or D14)/baseline x100%. | baseline vs EoT | Posted | Median | Inter-Quartile Range | percentage of baseline | Baseline to End of Treatment, or Day 14 |
|
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| 1 |
| 10 |
| 2 |
| 10 |
| 7 |
| 10 |
| EG001 | Placebo | Treated with matched placebo, orally, twice daily for 14 days Placebo: Placebo pill will be taken twice daily preferably spaced 12 hours apart. | 1 | 10 | 2 | 10 | 7 | 10 |
| hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| non-cardiac chest pain | Cardiac disorders | Non-systematic Assessment |
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| cardiac troponin | Cardiac disorders | Non-systematic Assessment |
|
| lymphocele | Blood and lymphatic system disorders | Non-systematic Assessment |
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| hematuria | Renal and urinary disorders | Non-systematic Assessment |
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| gout | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| hyperglycemia | Endocrine disorders | Non-systematic Assessment |
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| arthritis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| sinus bradycardia | Cardiac disorders | Non-systematic Assessment |
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| GGT increased | Hepatobiliary disorders | Non-systematic Assessment |
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| aspartate aminotransferase increase | Hepatobiliary disorders | Non-systematic Assessment |
|
| alanine aminotransferase increase | Hepatobiliary disorders | Non-systematic Assessment |
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| creatinine increased | Renal and urinary disorders | Non-systematic Assessment |
|
| skin hyperpigmentation | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
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| extremity pain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| sinus tachycardia | Cardiac disorders | Non-systematic Assessment |
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| gastrointestinal pain | Gastrointestinal disorders | Non-systematic Assessment |
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| non-cardiac chest pain | Cardiac disorders | Non-systematic Assessment |
|
| hypoxia | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| thrush | Infections and infestations | Non-systematic Assessment |
|
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| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| baseline to Day 14 |
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| baseline to Day 28 |
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| Grade 3 |
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| Grade 4 |
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| Grade 5 |
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| Grade 3 |
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| Grade 4 |
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| Grade 5 |
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