Covid19Phase 2NCT04481685
A Trial of Aclaris Therapeutics, Inc. (ATI)-450 in Patients With Moderate-severe Novel Coronavirus Disease 2019 (COVID-19)
A Phase 2 study testing ATI-450 in people with Covid19, run by University of Kansas Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19
- What is being tested?
- ATI-450
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 20 Jul 2020to 1 Jun 2021
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: 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.
- Conditions
- Covid19
- Being tested
- ATI-450, Placebo
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ATI-450Drug
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.
PlaceboDrug
Placebo pill will be taken twice daily preferably spaced 12 hours apart.
| Study group | Role | What they receive |
|---|---|---|
| ATI-450 | Active comparator | Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days Receives: Drug: ATI-450 |
| Placebo | Placebo comparator | Treated with matched placebo, orally, twice daily for 14 days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Study day 14
Secondary outcomes (13)
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).
Measured: 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
Measured: Baseline and continuous throughout hospitalization up to 14 days
All-cause Mortality
Noted in participant medical record
Measured: 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.
Measured: 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.
Measured: Up to Day 60
Number of Participants With Normalization of Fever for 24 Hours
Standard daily temperature measurement and obtained from participant medical record
Measured: Baseline through day 14 or at discharge <day 14
Number of Participants Who Develop New Bacterial Infection
Noted in participant medical record
Measured: Continuous throughout hospitalization up to 14 days
Number of Participants Who Develop New Fungal Infection
Noted in participant medical record
Measured: Continuous throughout hospitalization up to 14 days
Number of Adult Respiratory Distress Syndrome (ARDS2)
Noted in participant medical record
Measured: 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%.
Measured: 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%.
Measured: 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%.
Measured: 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%.
Measured: Baseline to End of Treatment, or Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2020
- Study start20 Jul 2020
- Primary completion25 Feb 2021
- Study completion1 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by University of Kansas Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Kansas Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Gregory Gan, MD, PhD, Principal investigator, The University of KansasDeepika Polineni, MD, PhD, Principal investigator, The University of Kansas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04481685
- Sponsor's protocol ID
- IIT-2020-ATI-450-COVID-19
- Status last verified
- May 2025
- First submitted
- 15 Jul 2020
- Last updated
- 4 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19
- ClinicalTrials.gov ID
- NCT04481685
- Acronym / sponsor ID
- IIT-2020-ATI-450-COVID-19
- Conditions
- Covid19
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- University of Kansas Medical CenterUniversity, hospital or other
- Study start
- 20 Jul 2020 (actual)
- Primary completion
- 25 Feb 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 22 Jul 2020 (actual)
- Results
- Posted 4 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ATI-450 | Active comparator | Drug: ATI-450Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days |
| Placebo | Placebo comparator | Drug: PlaceboTreated with matched placebo, orally, twice daily for 14 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ATI-45050 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. | Drug | ATI-450 |
| PlaceboPlacebo pill will be taken twice daily preferably spaced 12 hours apart. | Drug | Placebo |
Primary outcome
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.
13 secondary outcomes
Change in 7 Point-ordinal Scale
Time frame: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months
Number of Participants With a Need for Advanced Respiratory Care
Time frame: Baseline and continuous throughout hospitalization up to 14 days
All-cause Mortality
Time frame: Baseline and through day 60
Treatment-emergent Adverse Events
Time frame: Up to Day 60
Treatment-emergent Serious Adverse Events
Time frame: Up to Day 60
Number of Participants With Normalization of Fever for 24 Hours
Time frame: Baseline through day 14 or at discharge <day 14
Number of Participants Who Develop New Bacterial Infection
Time frame: Continuous throughout hospitalization up to 14 days
Number of Participants Who Develop New Fungal Infection
Time frame: Continuous throughout hospitalization up to 14 days
Number of Adult Respiratory Distress Syndrome (ARDS2)
Time frame: From day 1 though day 14 or at discharge <day 14
Change in Serum Cytokine Interleukin (IL)-6
Time frame: Baseline to End of Treatment, or Day 14
Change in Serum Cytokine IL-8
Time frame: Baseline to End of Treatment, or Day 14
Change in Serum Cytokines IL-1β
Time frame: Baseline to End of Treatment, or Day 14
Change in Serum Cytokine Tumor Necrosis Factor (TNF-α)
Time frame: Baseline to End of Treatment, or Day 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gregory Gan, MD, PhD principal investigator
The University of Kansas
Deepika Polineni, MD, PhD principal investigator
The University of Kansas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing ATI-450 in people with Covid19, run by University of Kansas Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450 (time frame: Study day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2025.