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

Study Overview
=================
Brief Summary
-----------------
A phase 2, placebo-controlled study of the safety and efficacy of STI-5656 (Abivertinib Maleate) in subjects hospitalized due to COVID-19

Detailed Description
-----------------
This is a phase 2, randomized, double-blind, placebo-controlled study of the safety and efficacy of STI-5656 (Abivertinib Maleate) in subjects hospitalized due to COVID-19 in Brazil. Subjects are randomized 3:1 STI-5656 to placebo. Subjects receive either 100 mg of STI-5656 or placebo daily for 7 days. Standard of care will be maintained for all subjects throughout the study.

Official Title
-----------------
A Phase 2, Randomized, Double-Blind, Placebo-controlled Study of the Safety and Efficacy of STI-5656 (Abivertinib Maleate) in Subjects Hospitalized Due to COVID-19

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Drug: STI-5656
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Confirmed positive for COVID-19 by RT-PCR assay or equivalent Subject or family member/caregiver must have provided written informed consent which includes signing the institutional review board (IRB) or independent ethics committee (IEC) 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 27, 2020 (Updated on July 2, 2020) FDA Guidance on Conduct of Clinical Trials of Medical Products during COVID-19 Pandemic, Question 10, may be used Able to swallow capsules Willing to follow contraception guidelines Exclusion Criteria: Pregnant or breast feeding Suspected uncontrolled active bacterial, fungal, viral, or other infection other than COVID-19 Treatment with a strong cytochrome p450 3A4 inhibitor or inducer within 7 days prior to Day 1 Received anti-rejection or immunomodulatory drugs within 14 days prior to Day 1 Concurrent participation in another clinical trial involving therapeutic interventions (observation studies are acceptable) Any condition that confounds the ability to interpret data from the study Any significant medical condition, laboratory abnormality, or psychiatric illness that would interfere with or prevent the subject from participating in the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: STI-5656<br>STI-5656 (abivertinib maleate) capsules administered orally 100 mg QD for 7 days, in addition to standard of care | Drug: STI-5656<br>* STI-5656 (abivertinib maleate) is a third-generation EGFR tyrosine kinase inhibitor and BTK Inhibitor.<br>* Other names: abivertinib;|
| Placebo Comparator: Placebo<br>Placebo capsules administered orally daily for 7 days, in addition to standard of care | Drug: Placebo<br>* Placebo capsules<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects discharged from hospital | Proportion of subjects whoa re alive and discharged from the hospital by Day 29 | Randomization through Day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of adverse events (safety) | Types, frequencies, and severities of adverse events and their relationships to STI-5656, including serious adverse events | Randomization through study completion through Day 36 | 
| Time to hospital admission, treatment, and discharge | Time from onset of COVID-19 symptoms to hospital admission, time from hospitalization to start of treatment (D1), and time from D1 to hospital discharge | Randomization through study completion through Day 36 | 
| Number of days hospitalized | Number of days hospitalized from randomization through Day 36 | Randomization to Day 36 | 
| Change in clinical status as assessed using a 0-8 ordinal scale | Change in clinical status as assessed using a 0-8 ordinal scale, where a lower score equals better outcome, at Days 3, 10, and 36 | Randomization to Day 3, Day 10, and Day 36 | 
| Change in RT-PCR test results | Change in RT-PCR test results (or equivalent) at Days 3, 10, and 36 | Randomization to Day 3, Day 10, and Day 36 | 
| Change in C-reactive protein levels | Change in C-reactive protein (CRP) levels at Day 3 and Day 10 | Randomization to Day 3 and Day 10 | 
| AUC of STI-5656 (PK) | Area under the serum concentration-time curve (AUC) of STI-5656 | Randomization through Day 8 | 
| Cmax of STI-5656 (PK) | Maximum observed serum concentration (Cmax) of STI-5656 | Randomization through Day 8 | 
| t½ of STI-5656 (PK) | Apparent serum terminal elimination half life (t½) of STI-5656 | Randomization through Day 8 | 
| Change in cytokine levels | Change in cytokine levels (including IL-6, TNF-a, IFNγ, IL1β) at Day 3 and Day 10 | Randomization to Day 3 and Day 10 | 
| Tmax of STI-5656 (PK) | Time to Cmax (Tmax) of STI-5656 | Randomization through Day 8 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
covid-19