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Completed

NCT Number: NCT04481685

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

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Key information

Conditions

Covid19 COVID-19 Coronaviridae Infections Coronavirus Infections Infections Lung Diseases Nidovirales Infections Pneumonia Pneumonia, Viral RNA Virus Infections Respiratory Tract Diseases Respiratory Tract Infections Virus Diseases

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

The University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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.

Placebo

Drug

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

Primary outcomes

  1. Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450

    Time frame: Study day 14

    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.

Secondary outcomes

  1. Change in 7 Point-ordinal Scale

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

    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).

  2. Number of Participants With a Need for Advanced Respiratory Care

    Time frame: Baseline and continuous throughout hospitalization up to 14 days

    Derived from medical record

  3. All-cause Mortality

    Time frame: Baseline and through day 60

    Noted in participant medical record

  4. Treatment-emergent Adverse Events

    Time frame: Up to Day 60

    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.

  5. Treatment-emergent Serious Adverse Events

    Time frame: Up to Day 60

    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.

  6. Number of Participants With Normalization of Fever for 24 Hours

    Time frame: Baseline through day 14 or at discharge <day 14

    Standard daily temperature measurement and obtained from participant medical record

  7. Number of Participants Who Develop New Bacterial Infection

    Time frame: Continuous throughout hospitalization up to 14 days

    Noted in participant medical record

  8. Number of Participants Who Develop New Fungal Infection

    Time frame: Continuous throughout hospitalization up to 14 days

    Noted in participant medical record

  9. Number of Adult Respiratory Distress Syndrome (ARDS2)

    Time frame: From day 1 though day 14 or at discharge <day 14

    Noted in participant medical record

  10. Change in Serum Cytokine Interleukin (IL)-6

    Time frame: Baseline to End of Treatment, or Day 14

    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%.

  11. Change in Serum Cytokine IL-8

    Time frame: Baseline to End of Treatment, or Day 14

    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%.

  12. Change in Serum Cytokines IL-1β

    Time frame: Baseline to End of Treatment, or Day 14

    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%.

  13. Change in Serum Cytokine Tumor Necrosis Factor (TNF-α)

    Time frame: Baseline to End of Treatment, or Day 14

    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%.

Sponsors and collaborators

Lead sponsor

University of Kansas Medical Center

Other

Registry information

Official study title

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

Important dates

Study start
2020
Primary completion
2021
Study completion
2021
First posted
Jul 22, 2020
Registry last updated
Jun 4, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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