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

• ClinicalTrials.gov Identifier: NCT04481685
• Recruitment Status: Completed
• First Posted: July 22, 2020
• Last Update Posted: June 23, 2021
• Sponsor: University of Kansas Medical Center
• Information provided by (Responsible Party): University of Kansas Medical Center

Tracking Information

• First Submitted Date: July 15, 2020
• First Posted Date: July 22, 2020
• Last Update Posted Date: June 23, 2021
• Actual Study Start Date: July 20, 2020
• Actual Primary Completion Date: February 25, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 20, 2020)

Respiratory failure-free survival in participants with moderate-severe COVID-19 who are treated with ATI-450 [ Time Frame: Study day 14 ]

Participants medical record

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: July 20, 2020)

• 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: Proportion and time to participants with greater than 2 point improvement on the 7 point categorical scale. 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).
• Change in oxygen saturation-normalization [ Time Frame: Baseline and continuous throughout hospitalization up to 14 days ]
  Peripheral capillary pulse oximeter to measure: Oxygen Saturation (SpO2)/Fraction of Inspired Oxygen (FiO2) ratio over time, sustainment of normalization in 24 hours, and relative shifts in SpO2/FiO2 categories (<235, between 235 and 315, greater than 315) over time
• Need for advanced respiratory care [ Time Frame: Baseline and continuous throughout hospitalization up to 14 days ]
  Derived from medical record
• All-cause mortality [ Time Frame: Baseline and through day 60 ]
  Noted in participant medical record
• Percentage of adverse events (AEs) [ Time Frame: Baseline through day 14 or at discharge <day 14, at day 28, day 45 and day 60 ]
  CTCAE v5.0
• Percentage of serious adverse events (SAEs) [ Time Frame: Baseline through day 14 or at discharge <day 14, at day 28, day 45 and day 60 ]
  CTCAE v5.0
• Proportion 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
• Number of participants who develop new bacterial infection [ Time Frame: Continuous throughout hospitalization up to 14 days ]
  Noted in participant medical record
• Number of participants who develop new fungal infection [ Time Frame: Continuous throughout hospitalization up to 14 days ]
  Noted in participant medical record
• Incidence of Adult Respiratory distress Syndrome (ARDS2) [ Time Frame: From day 1 though day 14 or at discharge <day 14 ]
  Noted in participant medical record
• Change in serum cytokine Interleukin (IL)-6 [ Time Frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14) ]
  Serum collected from blood and assayed on Luminex panel performed by University of Kansas Medical Center (KUMC) Biobanking and Biomarker Validation (BBV) Core
• Change in serum cytokine IL-8 [ Time Frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14) ]
  Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
• Change in serum cytokines IL-1β [ Time Frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14) ]
  Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core
• Change in serum cytokine Tumor Necrosis Factor (TNF-α) [ Time Frame: Baseline, day 3, day 7 (or discharge <day 7), day 14 (or discharge >day 7 and <day 14) ]
  Serum collected from blood and assayed on Luminex panel performed by KUMC BBV Core

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Trial of Aclaris Therapeutics, Inc. (ATI)-450 in Patients With Moderate-severe Novel Coronavirus Disease 2019 (COVID-19)
• Official Title: A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Care Provider); Primary Purpose: Treatment
• Condition: Covid19

Intervention

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

Study Arms

• Active Comparator: ATI-450
  Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days
  Intervention: Drug: ATI-450
• Placebo Comparator: Placebo
  Treated with matched placebo, orally, twice daily for 14 days
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 2, 2021): 20
• Original Estimated Enrollment (submitted: July 20, 2020): 36
• Actual Study Completion Date: June 1, 2021
• Actual Primary Completion Date: February 25, 2021 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04481685
• Other Study ID Numbers: IIT-2020-ATI-450-COVID-19
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: University of Kansas Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Kansas Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

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

• PRS Account: University of Kansas Medical Center
• Verification Date: May 2020