A Double-blind, Randomized, Controlled Trial of ATI-450 in Patients With Moderate-severe COVID-19

University of Kansas Medical Center1 site in 1 country20 target enrollmentJuly 20, 2020

ConditionsCovid19

InterventionsATI-450 Placebo

DrugsATI-450 Placebo

Overview

Phase: Phase 2
Intervention: ATI-450
Conditions: Covid19
Sponsor: University of Kansas Medical Center
Enrollment: 20
Locations: 1
Primary Endpoint: Respiratory Failure-free Survival in Participants With Moderate-severe COVID-19 Who Are Treated With ATI-450
Status: Completed
Last Updated: 11 months ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

July 20, 2020

End Date

June 1, 2021

Last Updated

11 months ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

University of Kansas Medical Center

Responsible Party

Sponsor

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
•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

Arms & Interventions

ATI-450

Treated with 50 mg dose of ATI-450, orally, twice daily for 14 days

Intervention: ATI-450

Placebo

Treated with matched placebo, orally, twice daily for 14 days

Intervention: Placebo

Outcomes

Primary Outcomes

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.

Secondary Outcomes

All-cause Mortality(Baseline and through day 60)
Treatment-emergent Adverse Events(Up to Day 60)
Treatment-emergent Serious Adverse Events(Up to Day 60)
Number of Participants With Normalization of Fever for 24 Hours(Baseline through day 14 or at discharge <day 14)
Number of Participants Who Develop New Bacterial Infection(Continuous throughout hospitalization up to 14 days)
Number of Participants Who Develop New Fungal Infection(Continuous throughout hospitalization up to 14 days)
Number of Adult Respiratory Distress Syndrome (ARDS2)(From day 1 though day 14 or at discharge <day 14)
Change in Serum Cytokine Interleukin (IL)-6(Baseline to End of Treatment, or Day 14)
Change in Serum Cytokine IL-8(Baseline to End of Treatment, or Day 14)
Change in Serum Cytokines IL-1β(Baseline to End of Treatment, or Day 14)
Change in Serum Cytokine Tumor Necrosis Factor (TNF-α)(Baseline to End of Treatment, or Day 14)
Change in 7 Point-ordinal Scale(Baseline, Day 7, Day 14, Day 28 and follow-up up to 9 months)
Number of Participants With a Need for Advanced Respiratory Care(Baseline and continuous throughout hospitalization up to 14 days)