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

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

Detailed Description
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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.

Official Title
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A Phase 2, Open Label, Randomized Study of the Efficacy and Safety of STI-5656 (Abivertinib Maleate) With Standard of Care Versus Standard of Care in Subjects Hospitalized With COVID-19

Conditions
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Covid-19

Intervention / Treatment
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* Drug: Abivertinib
* Other: Standard of Care


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Abivertinib with Standard of Care<br>STI-5656 (abivertinib maleate) capsule administered orally 200 mg QD up to 28 days or until hospital discharge, in addition to standard of care | Drug: Abivertinib<br>* Abivertinib maleate is a third-generation EGFR tyrosine kinase inhibitor and BTK Inhibitor. The starting dose is 200 mg p.o. QD for up to 28 days.<br>* Other names: STI-5656;Other: Standard of Care<br>* Standard of Care as determined by the Investigator<br>|
| Active Comparator: Standard of Care<br>Standard of care treatments for COVID-19 as determined appropriate by the Investigator | Other: Standard of Care<br>* Standard of Care as determined by the Investigator<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Alive and Free of Respiratory Failure at 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 | Randomization to Day 28 | 

Secondary Outcome Measures

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