a trial of aclaris therapeutics, inc. (ati)-450 in patients with moderate-severe novel coronavirus disease 2019 (covid-19)

Conditions: Covid19

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.


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 \ 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