COVID-19
Conditions
Keywords
Pulmonary fibrosis, COVID-19, SARS-COV-2, ROS
Brief summary
This phase 2 study is to assess the safety and tolerability of APX-115 active doses compared to placebo following multiple oral dosing in hospitalized patients with confirmed, mild to moderate, symptomatic COVID-19. It is anticipated that approximately 80 patients will be randomized into the study in a 1:1 ratio to 100 mg APX-115 or placebo arm.
Detailed description
APX-115 is a potent small molecule inhibitor of NADPH-oxidase (Nox) isozymes being developed by Aptabio Therapeutics Inc. The Nox enzymes represent a family of 7 membrane enzymes (Nox1, Nox2, Nox3, Nox4, Nox5, Duox1, and Duox2) which catalyze NADPH-dependent generation of superoxide and secondary reactive oxygen species (ROS). ROS are often generated during virus infection, thus promoting apoptosis, lung injury, and inflammation/allergy.
Interventions
DRUGAPX-115
Oral administration of APX-115 100 mg capsule once daily for 14 days
DRUGPlacebo
Oral administration of placebo capsule once daily for 14 days
Sponsors
Aptabio Therapeutics, Inc.
Covance
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Willing and able to provide informed consent themselves or through their legally authorized representative. 2. Male or female patients, of any race or ethnicity, 18 to 80 years of age, inclusive, on the day of informed consent. Racial and ethnic minorities should be included in the study population to the greatest extent possible. 3. Laboratory-confirmed SARS-CoV-2 infection as determined within 14 days of randomization by real time RT-PCR or other commercial or public health assay authorized by FDA or other applicable health authority . 4. Onset of COVID-19 symptoms within 14 days prior to randomization. 5. Have at least one of the following symptoms at screening: fever, cough, shortness of breath, myalgia, ageusia, anosmia, fatigue, or weakness. 6. Hospitalized with COVID-19 disease (WHO COVID-19 Clinical Improvement Ordinal Scale score of 3 \[hospitalized, no oxygen therapy\], 4 \[hospitalized, oxygen by mask or nasal prongs\], or 5 \[high-flow oxygen or non-invasive mechanical ventilation\]) 7. Patient is aware of the investigational nature of this study and willing to comply with protocol treatments, blood tests, and other evaluations listed in the informed consent form.
Exclusion criteria
1. Females who are pregnant (negative pregnancy test required for all women of childbearing potential at screening) or breastfeeding. 2. Male patients and women of childbearing potential (women who are not surgically sterile or postmenopausal defined as postmenopausal for \>12 months) who are not using at least one protocol specified method of contraception. 3. COVID-19 disease as defined by the WHO COVID-19 Clinical Improvement Ordinal Scale, scores of 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, renal replacement therapy, extracorporeal membrane oxygenation). 4. Expected survival less than 72 hours. 5. Treatment with other drugs thought to possibly have activity against SARS CoV 2 infection within 7 days or within 5 half-lives, whichever is longer, prior to enrollment or concurrently. Drugs that have received FDA emergency use authorization or COVID-19 approval are allowed. 6. Treatment with immunosuppressants, combination of 2 or more RAS blockers, UGT inhibitors and inducers, herbal/natural supplements, potassium-sparing diuretic, and radiographic contrast agent prior to enrollment or concurrently. 7. History of abuse of drugs or alcohol that could interfere with adherence to study requirements as judged by the investigator. 8. Use of any other concurrent investigational drugs while participating in the present study. 9. Patient requires frequent or prolonged use of systemic corticosteroids (≥20 mg of prednisone/day or equivalent for \>4 weeks) or other immunosuppressive drugs (eg, for organ transplantation or autoimmune conditions). 10. Known renal disease with an estimated glomerular filtration rate \<30 mL/min. 11. Patients with clinically apparent liver disease (eg, jaundice, cholestasis, hepatic synthetic impairment, or active hepatitis) or moderate or severe hepatic impairment as determined by Child-Pugh score Class B or C. 12. Alanine aminotransaminase (ALT) or aspartate aminotransaminase (AST) \>3 × upper limit of normal (ULN) AND total bilirubin levels \>2 × ULN OR ALT or AST \>5 × ULN. 13. Total bilirubin \>1.5 × ULN, unless the patient has known Gilbert's syndrome. 14. Hemoglobin \<9 g/dL for females or \<11 g/dL for males. 15. Absolute neutrophil count \<1500/mm3. 16. Thrombocytopenia (platelets count \<100 × 109/L). 17. Inability to swallow oral medications or a gastrointestinal disorder with diarrhea (eg, Crohn's disease) or malabsorption at screening. 18. Any other clinically significant medical condition or laboratory abnormality that, in the opinion of the investigator, would jeopardize the safety of the patient or potentially impact patient compliance or the safety/efficacy observations in the study. 19. History of an allergic reaction or hypersensitivity to the study drug or any component of the study drug formulation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of Treatment-Emergent Adverse Events | over the 60-day period | Adverse events will be assessed to evaluate the safety and tolerability of APX-115 in mild-to-moderate COVID-19 patients. Clinical laboratory evaluations, vital signs, and ECG will be used to assess adverse events. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Clinical Recovery | Up to 29 Days | Recovery is defined as when WHO Clinical Improvement Ordinal Scale equal to or less than 3. WHO Clinical Improvement Ordinal Scale Uninfected : -No clinical or virological evidence of infection 0 Ambulatory: * No limitation of activities 1 * Limitation of activities 2 Hospitalized Mild disease: * Hospitalized, no oxygen therapy 3 * Oxygen by mask or nasal prongs 4 Hospitalized Severe Disease: * Non-invasive ventilation or high-flow oxygen 5 * Intubation and mechanical ventilation 6 * Ventilation + additional organ support - pressors, RRT, ECMO 7 Dead : \- Death 8 |
| Time to Discharge | Up to Day 29 | WHO Clinical Improvement Ordinal Scale is equal to or less than 2. WHO Clinical Improvement Ordinal Scale Uninfected : -No clinical or virological evidence of infection 0 Ambulatory: * No limitation of activities 1 * Limitation of activities 2 Hospitalized Mild disease: * Hospitalized, no oxygen therapy 3 * Oxygen by mask or nasal prongs 4 Hospitalized Severe Disease: * Non-invasive ventilation or high-flow oxygen 5 * Intubation and mechanical ventilation 6 * Ventilation + additional organ support - pressors, RRT, ECMO 7 Dead : \- Death 8 |
| Proportion of Patients in Clinical Recovery | up to 29 days | Symptom Assessment of patients in clinical recovery |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 6 study centers in the US from 20 Oct 2021 to 28 Apr 2022 (Last Participant Last Visit). The sponsor decided to discontinue/terminate the study on 14 Apr 2023 due to an inability to recruit subjects from a shift in the COVID-19 pandemic.
Pre-assignment details
A total of 16 patients were randomized to treatment in the sentinel cohort. Of these, 8 patients were administered at least 1 dose of APX-115, 7 patients were administered at least 1 dose of placebo, and 1 patient was randomized in error.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Customized | 60.5 Years STANDARD_DEVIATION 11.5 |
| Height | 174.419 cm STANDARD_DEVIATION 11.1747 |
| Race/Ethnicity, Customized American Indian or Alaska Native | 0 Participants |
| Race/Ethnicity, Customized Asian | 0 Participants |
| Race/Ethnicity, Customized Black or African American | 2 Participants |
| Race/Ethnicity, Customized White | 6 Participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 3 Participants |
| Weight | 92.61 kg STANDARD_DEVIATION 24.804 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 1 / 8 | 1 / 7 |
| other Total, other adverse events | 5 / 8 | 3 / 7 |
| serious Total, serious adverse events | 1 / 8 | 1 / 7 |
Outcome results
None listed