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.
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.
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
The University of Kansas Medical Center
Kansas City, Kansas, United States