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

NCT04481685 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IIT-2020-ATI-450-COVID-19
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (13)

• Change in 7 Point-ordinal Scale

  Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months

• Number of Participants With a Need for Advanced Respiratory Care

  Baseline and continuous throughout hospitalization up to 14 days

• All-cause Mortality

  Baseline and through day 60

• Treatment-emergent Adverse Events

  Up to Day 60

• Treatment-emergent Serious Adverse Events

  Up to Day 60

Study Arms (2)

ATI-450

ACTIVE COMPARATOR

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

Drug: ATI-450

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

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.

ATI-450

Placebo DRUG

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

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Kansas Medical Center: lead

Study Sites (1)

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Results Point of Contact

• Title: Gregory Gan, MD PhD
• Organization: University of Kansas Medical Center

ggan@kumc.edu

913 588 5881

Study Officials

• Gregory Gan, MD, PhD

  The University of Kansas

  PRINCIPAL INVESTIGATOR

• Deepika Polineni, MD, PhD

  The University of Kansas

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2020
• First Posted: July 22, 2020
• Study Start: July 20, 2020
• Primary Completion: February 25, 2021
• Study Completion: June 1, 2021
• Last Updated: June 4, 2025
• Results First Posted: June 4, 2025

Record last verified: 2025-05

Locations

US (1)