A Phase 2 Study of APX-115 in Hospitalized Patients With Confirmed Mild to Moderate COVID-19.

COVID-19 Clinical Trial

Official title:

A Phase 2, Double-blind, Placebo-controlled, Efficacy, and Safety Study of APX-115 in Hospitalized Patients With Confirmed Mild to Moderate COVID-19.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04880109
• Other study ID #: A01-115-03
• Status: Terminated
• Phase: Phase 2
• Start date: October 20, 2021
• Est. completion date: April 28, 2022

Study information

• Verified date: January 2024
• Source: Aptabio Therapeutics, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 16
• Est. completion date: April 28, 2022
• Est. primary completion date: April 28, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• COVID-19

Intervention

Drug:
• APX-115
Oral administration of APX-115 100 mg capsule once daily for 14 days
• Placebo
Oral administration of placebo capsule once daily for 14 days

Locations

Country	Name	City	State
United States	Anne Arundel Medical Center	Baltimore	Maryland
United States	Alternative Research Associates, LLC	Hialeah	Florida
United States	Millennium Physicians Group	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
Aptabio Therapeutics, Inc.	Covance

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Incidence of Treatment-Emergent Adverse Events	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.	over the 60-day period
Secondary	Time to clinical recovery	Recovery is defined as when WHO Clinical Improvement Ordinal Scale equal to or less than 3	Up to 60 Days
Secondary	Time to discharge	WHO Clinical Improvement Ordinal Scale is equal to or less than 2	Up to Day 60
Secondary	Time to symptomatic recovery	When none of the COVID-19 Symptom Assessment scores are higher than 1	Up to Day 60
Secondary	Time to complete symptomatic recovery	When none of the COVID-19 Symptom Assessment scores are higher than 0	Up to Day 60
Secondary	Change in log10 SARS-CoV-2 viral load	hange from baseline in log10 SARS-CoV-2 viral load as measured by RT-PCR by Days 5 and 14	Up to Day 14
Secondary	Proportion of patients in clinical recovery	Symptom Assessment	Up to Day 29
Secondary	scoring of WHO Clinical Improvement Ordinal Scale	9-point scale on key analysis days for levels =3	Up to Day 29
Secondary	Changes from baseline in anti-inflammatory markers in blood	Blood will be analyzed for changes from baseline in anti-inflammatory markers, such as C-reactive protein, ferritin, lactate dehydrogenase, D-dimer, troponin, and transforming growth factor-ß.	Day 1 and Day 14
Secondary	Changes from baseline in pro-inflammatory cytokines in blood	Blood will be analyzed for changes from baseline in pro-cytokine panel of the blood, such as interleukin (IL)-1ß, IL-6, and interferon-?.	Day 1 and 14
Secondary	Changes from baseline in 8-isoprostane in blood	Blood will be analyzed for changes from baseline in 8-isoprostane.	Days 1 and 14
Secondary	Trough (predose) plasma concentration (Ctrough)	Trough (predose) plasma concentration (Ctrough) will be analyzed from plasma samples for pharmacokinetic assessment of APX-115.	Day 1
Secondary	Maximum observed plasma concentration (Cmax)	Maximum observed plasma concentration (Cmax) will be analyzed from plasma samples for pharmacokinetic assessment of APX-115.	Days 1, 5, and 14
Secondary	Time to Cmax (Tmax)	Time to Cmax (Tmax) will be analyzed from plasma samples for pharmacokinetic assessment of APX-115.	Days 1, 5, and 14
Secondary	Area under the plasma concentration versus time curve (AUC) from time zero to the Time of last quantifiable concentration (AUC0-last)	Area under the plasma concentration versus time curve (AUC) from time zero to the time of last quantifiable concentration (AUC0-last) will be analyzed from plasma samples for pharmacokinetic assessment of APX-115.	Days 1, 5, and 14
Secondary	AUC within a dosing interval (AUCtau, where tau = 12 hours)	AUC within a dosing interval (AUCtau, where tau = 12 hours) will be analyzed from plasma samples for pharmacokinetic assessment of APX-115.	Days 1, 5, and 14