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

NCT ID: NCT04481685

Last Updated: 2025-06-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-20
• Study Completion Date: 2021-06-01

Brief Summary

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.

Conditions

Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

ATI-450

Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days

Group Type: ACTIVE_COMPARATOR

ATI-450

Intervention Type: 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.

Placebo

Treated with matched placebo, orally, twice daily for 14 days

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo pill will be taken twice daily preferably spaced 12 hours apart.

Interventions

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.

Intervention Type: DRUG

Placebo

Placebo pill will be taken twice daily preferably spaced 12 hours apart.

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Kansas Medical Center

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gregory Gan, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Kansas

Deepika Polineni, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Kansas

Locations

The University of Kansas Medical Center

Kansas City, Kansas, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

IIT-2020-ATI-450-COVID-19

Identifier Type: -

Identifier Source: org_study_id