A Trial of Aclaris Therapeutics, Inc. (ATI)-450 in Patients With Moderate-severe Novel Coronavirus Disease 2019 (COVID-19)

A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

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.

Study Overview

• Status: Completed
• Conditions: Covid19
• Intervention / Treatment: Drug: ATI-450; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • The University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Able to comprehend and be willing to sign the Institutional Review Board (IRB)-approved subject informed consent form (ICF) prior to administration of any study-related procedures, or consent from surrogate decision maker when the above criteria cannot be met
• Male or non-pregnant female adult ≥18 years of age at time of enrollment; female patients must have a negative serum pregnancy test at study enrollment
• Has laboratory-confirmed COVID-19 coronavirus infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in oropharyngeal or nasopharyngeal testing within 14 days of hospitalization. An additional 24-hour COVID-19 PCR test will be performed at KUMC. Patients outside of KUMC will have their samples sent to KUMC as a Central Lab for test processing
• Hospitalized as a result of symptoms and signs related to COVID-19 infection, and ≤14 days since positive test
• Evidence of hypoxic respiratory failure: SpO2≤93% on room air, or SpO2 >93% requiring ≥ 2 Liters (L) O2, or Pa02/Fi02 ratio <300 Millimeter of Mercury (mmHg), or tachypnea (respiratory rate > 30 breaths/min)
• Evidence of pulmonary involvement by: chest imaging or pulmonary exam
• Previous use of hydroxychloroquine or chloroquine is allowed in this study
• Adequate organ function per laboratory tests
• Females of child-bearing potential and males with partners of child-bearing potential must agree to practice sexual abstinence or to use the forms of contraception listed in Child-Bearing Potential/Pregnancy section for the duration of study participation and for 30 Days for females and 90 days for males following completion of therapy

Exclusion Criteria:

• Known hypersensitivity to ATI-450
• History or evidence of active or latent tuberculosis or recent exposure (within last 30d) to a person with active Tb
• Evidence of active, untreated bacterial infection. Patients who are treated with antibiotics for at least 72 hours, will become eligible for rescreening for trial enrollment
• Active use of immunosuppressant medication(s) (i.e. anti-rejection ,immunomodulators or immunosuppressant drugs, including but not limited to IL-6 inhibitors, TNF inhibitors, anti-IL-1 agents and Janus kinase (JAK) inhibitors within 5 half-lives or 30 days (whichever is longer) prior to randomization. (Use of hydroxychloroquine/chloroquine should be discontinued)
• Oncology patients who are on active chemotherapy or immunotherapy. However, oncology patients who come off active therapy prior to enrollment and have absolute neutrophil count (ANC) ≥1500/mmc are eligible for enrollment
• Active participation in a concurrent COVID-19 clinical trial with investigative medical drug therapies. However, co-enrollment for non-investigative drug therapies will be allowed; use or re-purposing of FDA approved treatments will be considered at the discretion of the medical monitor
• In the opinion of the investigator, unlikely to survive for at least 48 hours from screening or anticipate mechanical ventilation within 48 hours
• Pregnancy or breast feeding
• Prisoner
• Intubation and ventilation at time of enrollment
• Known history for HIV, hepatitis B or C infection. Patients with serologic evidence of hepatitis B vaccination (hepatitis B surface antibody without the presence of hepatitis B surface antigen) will be allowed to participate
• History of a past or current medical condition that in the opinion of the treating physician would compromise patient safety (e.g. uncontrolled HIV) by participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: ATI-450; Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days	Drug: 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.
Placebo Comparator: Placebo; Treated with matched placebo, orally, twice daily for 14 days	Drug: Placebo; Placebo pill will be taken twice daily preferably spaced 12 hours apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.; 0- Uninfected: No clinical or virological evidence of infection.; 1- Ambulatory: No limitation of activities.; 2- Ambulatory: Limitation of activities.; 3- Hospitalized, mild disease: Hospitalized, no oxygen.; 4- Hospitalized, mild disease: Oxygen by mask or nasal prongs.; 5- Hospitalized, severe disease: Non- invasive ventilation or high- flow oxygen.; 6- Hospitalized, severe disease: Intubation and mechanical ventilation.; 7- Hospitalized, severe disease: Ventilation + organ support; pressors, Renal Replacement Therapy (RRT), Extracorporeal Membrane Oxygenation (ECMO).	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

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Investigators: Principal Investigator: Gregory Gan, MD, PhD, The University of Kansas; Principal Investigator: Deepika Polineni, MD, PhD, The University of Kansas

Study record dates

Study Major Dates

• Study Start (Actual): July 20, 2020
• Primary Completion (Actual): February 25, 2021
• Study Completion (Actual): June 1, 2021

Study Registration Dates

• First Submitted: July 15, 2020
• First Submitted That Met QC Criteria: July 20, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): June 4, 2025
• Last Update Submitted That Met QC Criteria: May 15, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19
• Other Study ID Numbers: IIT-2020-ATI-450-COVID-19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No