Clinical trial NCT04481685: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Covid19
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2020-07-22
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450
timeFrame: Study day 14
Secondary outcomes:
measure: Change in 7 Point-ordinal Scale
timeFrame: Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months
measure: Number of Participants With a Need for Advanced Respiratory Care
timeFrame: Baseline and continuous throughout hospitalization up to 14 days
measure: All-cause Mortality
timeFrame: Baseline and through day 60
measure: Treatment-emergent Adverse Events
timeFrame: Up to Day 60
measure: Treatment-emergent Serious Adverse Events
timeFrame: Up to Day 60
measure: Number of Participants With Normalization of Fever for 24 Hours
timeFrame: Baseline through day 14 or at discharge <day 14
measure: Number of Participants Who Develop New Bacterial Infection
timeFrame: Continuous throughout hospitalization up to 14 days
measure: Number of Participants Who Develop New Fungal Infection
timeFrame: Continuous throughout hospitalization up to 14 days
measure: Number of Adult Respiratory Distress Syndrome (ARDS2)
timeFrame: From day 1 though day 14 or at discharge <day 14
measure: Change in Serum Cytokine Interleukin (IL)-6
timeFrame: Baseline to End of Treatment, or Day 14
measure: Change in Serum Cytokine IL-8
timeFrame: Baseline to End of Treatment, or Day 14
measure: Change in Serum Cytokines IL-1β
timeFrame: Baseline to End of Treatment, or Day 14
measure: Change in Serum Cytokine Tumor Necrosis Factor (TNF-α)
timeFrame: Baseline to End of Treatment, or Day 14
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: The University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: The University of Kansas
name: Gregory Gan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: The University of Kansas
name: Deepika Polineni, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: