Covid-19
Conditions
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.
Interventions
DRUGAbivertinib
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.
OTHERStandard of Care
Standard of Care as determined by the Investigator
Sponsors
Sorrento Therapeutics, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| Change in C-Reactive Protein (CRP) | Day 7 | Mean change in CRP on Day 7 |
| Number of Participants With Treatment-emergent Adverse Events | Randomization through study completion to 94 days | Number of Participants with Treatment-emergent Adverse Events |
| 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 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 |
| Partial Pressure of Oxygen in Arterial Blood and Fraction of Inspired Oxygen (PaO2/FiO2) | Day 1 | PaO2/FiO2 at Day 1 |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Abivertinib With 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
Abivertinib: 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.
Standard of Care: Standard of Care as determined by the Investigator | 48 |
| Placebo With Standard of Care Oral placebo capsule administered orally QD up to 28 days or until hospital discharge, in addition to standard of care of care treatment for COVID-19 as determined appropriate by the Investigator
Standard of Care: Standard of Care as determined by the Investigator | 48 |
| Total | 96 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 1 |
| Overall Study | Death | 7 | 2 |
| Overall Study | Discontinued prior to dosing | 0 | 2 |
| Overall Study | Inability to draw blood for labs and being transferred to a nursing facility with no transportation | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 3 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 2 | 1 |
Baseline characteristics
| Characteristic | Abivertinib With Standard of Care | Total | Placebo With Standard of Care |
|---|---|---|---|
| Age, Customized Age | 59.9 years STANDARD_DEVIATION 12.38 | 58.6 years STANDARD_DEVIATION 12.63 | 57.4 years STANDARD_DEVIATION 12.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 9 Participants | 19 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 37 Participants | 73 Participants | 36 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 15 Participants | 11 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 42 Participants | 75 Participants | 33 Participants |
| Region of Enrollment United States | 48 participants | 96 participants | 48 participants |
| Sex: Female, Male Female | 17 Participants | 34 Participants | 17 Participants |
| Sex: Female, Male Male | 31 Participants | 62 Participants | 31 Participants |
| Weight | 101.94 kg STANDARD_DEVIATION 30.694 | 101.03 kg STANDARD_DEVIATION 28.243 | 100.12 kg STANDARD_DEVIATION 25.855 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 8 / 48 | 5 / 48 |
| other Total, other adverse events | 31 / 48 | 24 / 46 |
| serious Total, serious adverse events | 9 / 48 | 8 / 46 |
Outcome results
Primary
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
Time frame: Randomization to Day 28
Population: A total of 48 subjects in the STI-5656 group and 48 subjects in the placebo group were included in the analysis of the primary endpoint in the FAS. For a number of the excluded subjects, the reason for exclusion from the primary endpoint analysis was that they had no baseline value available.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abivertinib With Standard of Care | Percentage of Subjects Alive and Free of Respiratory Failure at Day 28 | 40 Participants |
| Placebo With Standard of Care | Percentage of Subjects Alive and Free of Respiratory Failure at Day 28 | 38 Participants |
Secondary
All-cause Mortality at Day 60 and Day 90
All-cause mortality at Day 60 and Day 90
Time frame: Day 60 and Day 90
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Abivertinib With Standard of Care | All-cause Mortality at Day 60 and Day 90 | Day 60 | 8 Participants |
| Abivertinib With Standard of Care | All-cause Mortality at Day 60 and Day 90 | Day 90 | 8 Participants |
| Placebo With Standard of Care | All-cause Mortality at Day 60 and Day 90 | Day 60 | 5 Participants |
| Placebo With Standard of Care | All-cause Mortality at Day 60 and Day 90 | Day 90 | 5 Participants |
Secondary
Change in C-Reactive Protein (CRP)
Mean change in CRP on Day 7
Time frame: Day 7
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| Abivertinib With Standard of Care | Change in C-Reactive Protein (CRP) | 71.43 ng/ml | Standard Deviation 527.102 |
| Placebo With Standard of Care | Change in C-Reactive Protein (CRP) | 66.67 ng/ml | Standard Deviation 755.613 |
Secondary
Number of Days Alive Outside of Hospital up to Day 28
Number of days alive outside of hospital up to Day 28
Time frame: Randomization up to Day 28
| Arm | Measure | Value (LEAST_SQUARES_MEAN) |
|---|---|---|
| Abivertinib With Standard of Care | Number of Days Alive Outside of Hospital up to Day 28 | 16.7 days |
| Placebo With Standard of Care | Number of Days Alive Outside of Hospital up to Day 28 | 17.1 days |
Secondary
Number of Participants With Treatment-emergent Adverse Events
Number of Participants with Treatment-emergent Adverse Events
Time frame: Randomization through study completion to 94 days
Population: A total of 48 subjects in the STI-5656 group and 46 subjects in the placebo group were included in the analysis of the secondary endpoint in the FAS. For a number of the excluded subjects, the reason for exclusion from the secondary endpoint analysis was that they had no baseline value available. 46 subjects were analyzed for the placebo group as 2 subjects were randomized to the placebo group who ET prior to dosing.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abivertinib With Standard of Care | Number of Participants With Treatment-emergent Adverse Events | 31 Participants |
| Placebo With Standard of Care | Number of Participants With Treatment-emergent Adverse Events | 23 Participants |
Secondary
Partial Pressure of Oxygen in Arterial Blood and Fraction of Inspired Oxygen (PaO2/FiO2)
PaO2/FiO2 at Day 1
Time frame: Day 1
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Abivertinib With Standard of Care | Partial Pressure of Oxygen in Arterial Blood and Fraction of Inspired Oxygen (PaO2/FiO2) | 210.61 mmHG | Standard Deviation 112.686 |
| Placebo With Standard of Care | Partial Pressure of Oxygen in Arterial Blood and Fraction of Inspired Oxygen (PaO2/FiO2) | 253.34 mmHG | Standard Deviation 103.679 |
Secondary
Percentage of Subjects Alive and Free of Respiratory Failure at Day 60
Percentage of subjects alive and free of respiratory failure at Day 60
Time frame: Randomization to Day 60
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Abivertinib With Standard of Care | Percentage of Subjects Alive and Free of Respiratory Failure at Day 60 | 37 Participants |
| Placebo With Standard of Care | Percentage of Subjects Alive and Free of Respiratory Failure at Day 60 | 35 Participants |