Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized With COVID-19

Phase 2

Completed

Brief Summary: Study to assess the safety and efficacy of STI-5656 (Abivertinib Maleate) plus SOC versus SOC in subjects hospitalized with COVID-19

Detailed Description: This is a Phase 2, open-label, randomized 2-arm multicenter study to assess the safety and efficacy of STI-5656 (Abivertinib Maleate) administered orally plus Standard of Care (SOC) versus SOC in hospitalized subjects with RT-PCR confirmed SARS-CoV-2 infection and COVID-19 pneumonia (documented radiographically). Only hospitalized patients are eligible for this study.

Recruitment & Eligibility

Inclusion Criteria

Confirmed infection with SARS-CoV-2 per World Health Organization (WHO) criteria (including positive RT-PCR nucleic acid test of any specimen [eg, respiratory, blood, urine, stool, or other bodily fluid]) within 7 days of randomization
Hospitalized with COVID-19 pneumonia (documented radiographically) and oxygen saturation <94% on room air or subject requires supplemental oxygen
Able to swallow capsules
Willing to follow contraception guidelines
Subject or family member/caregiver must have provided written informed consent which includes signing the institutional review board approved consent form prior to participating in any study related activity. However, if obtaining written informed consent is not possible, other procedures as provided in the March 27th, 2020 FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic, Question 10, may be used

Exclusion Criteria

Known cardio-pulmonary resuscitation within 14 days prior to randomization
Pregnant or breast feeding
Suspected uncontrolled active bacterial, fungal, viral, or other infection (besides infection with SARS-CoV-2)
Alanine aminotransferase (ALT) ≥ 3x upper limit of normal (ULN) and total bilirubin > 2x ULN
QTcF prolongation >480 milliseconds
Uncontrolled or untreated symptomatic arrhythmias, myocardial infarction within the last 6 weeks, or congestive heart failure (NYHA Grade 3 or 4). Exception: Subjects with controlled, asymptomatic atrial fibrillation during screening are allowed to enroll
Treatment with a strong cytochrome P450 (CYP3A4 inhibitor (within 14 days before first dose of study drug) or inducer (within 7 days before first dose of study drug)
Received anti-rejection or immunomodulatory drugs (eg, anti-cytokines, BTK inhibitors, JAK inhibitors, PI3K inhibitors) within 30 days before randomization on study
Concurrent participation in another clinical trial involving therapeutic interventions (observational study participation is acceptable)
Any condition that confounds the ability to interpret data from the study
Relevant renal impairment (eGFR <60 mL/min)
Any significant medical condition, laboratory abnormality or psychiatric illness that would interfere or prevent the subject from participating in the study

Arm && Interventions

Group	Intervention	Description
Standard of Care	Standard of Care	Standard of care treatments for COVID-19 as determined appropriate by the Investigator
Abivertinib with Standard of Care	Abivertinib	STI-5656 (abivertinib maleate) capsule administered orally 200 mg QD up to 28 days or until hospital discharge, in addition to standard of care
Abivertinib with Standard of Care	Standard of Care	STI-5656 (abivertinib maleate) capsule administered orally 200 mg QD up to 28 days or until hospital discharge, in addition to standard of care

Primary Outcome Measures

Name	Time	Method
Percentage of Subjects Alive and Free of Respiratory Failure at Day 28	Randomization to Day 28	Percentage of subjects alive and free of respiratory failure at Day 28, where respiratory failure, is defined based on resource utilization of any of the following modalities: * Noninvasive positive pressure ventilation or continuous positive airway pressure * Endotracheal intubation and mechanical ventilation * Oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates \>20L/min with fraction of delivered oxygen ≥ 0.5) * Extracorporeal membrane oxygenation

Secondary Outcome Measures

Name	Time	Method
Change in C-Reactive Protein (CRP)	Day 7	Mean change in CRP on Day 7
Partial Pressure of Oxygen in Arterial Blood and Fraction of Inspired Oxygen (PaO2/FiO2)	Day 1	PaO2/FiO2 at Day 1
All-cause Mortality at Day 60 and Day 90	Day 60 and Day 90	All-cause mortality at Day 60 and Day 90
Number of Participants With Treatment-emergent Adverse Events	Randomization through study completion to 94 days	Number of Participants with Treatment-emergent Adverse Events
Number of Days Alive Outside of Hospital up to Day 28	Randomization up to Day 28	Number of days alive outside of hospital up to Day 28
Percentage of Subjects Alive and Free of Respiratory Failure at Day 60	Randomization to Day 60	Percentage of subjects alive and free of respiratory failure at Day 60

Locations (6): MedStar Washington Hospital Center
🇺🇸
Washington, District of Columbia, United States
Teradan Clinical Trials
🇺🇸
Brandon, Florida, United States
Quality Clinical Research
🇺🇸
Omaha, Nebraska, United States
Memorial Hermann Memorial City Hospital
🇺🇸
Houston, Texas, United States
Alexandria Cardiology Clinic
🇺🇸
Alexandria, Louisiana, United States
Clinical Trials of SWLA
🇺🇸
Lake Charles, Louisiana, United States