Double-blind Study to Evaluate the Safety and Efficacy of Antroquinonol in Mild-Moderate COVID-19 Hospitalized Patients

Study Overview
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Brief Summary
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To evaluate the safety and efficacy of antroquinonol treatment of mild to moderate pneumonia due to COVID-19, as measured by the proportion of patients alive and free of respiratory failure.

Detailed Description
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This is a randomized, double blind, placebo controlled, Phase 2, proof of concept study in hospitalized patients with mild to moderate pneumonia due to COVID 19. Written informed consent must be obtained from all patients during screening. Following completion of all screening assessments and meeting of eligibility criteria, patients will either receive antroquinonol or placebo for 14 days in combination with SoC therapy per local SoC policies.

Official Title
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A Phase 2 Randomized, Double-blind, Placebo-controlled, Proof of Concept Study to Evaluate the Safety and Efficacy of Antroquinonol in Hospitalized Patients With Mild to Moderate Pneumonia Due to COVID-19

Conditions
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Covid-19

Intervention / Treatment
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* Drug: Antroquinonol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide informed consent. Male or female patients between 18 and 80 years of age. Oxygen Saturation <94% in room air at screening. Hospitalized with mild COVID 19 disease (not requiring oxygen therapy [WHO COVID-19 Clinical Improvement Ordinal Scale, score of 3] or requiring oxygen therapy by mask or nasal prong [WHO COVID-19 Clinical Improvement Ordinal Scale, score of 4]). Requirement of oxygen therapy by mask with reservoir to treat severe COVID 19 pneumonia is not allowed for enrollment. Note: Hospitalized patients can also include patients admitted to centers conditioned as hospitals to treat COVID-19 patients. Chest x ray or computerized tomography (CT) scan consistent with pneumonia. Onset of COVID-19 symptoms within 2 weeks prior to randomization. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS CoV 2) infection confirmed by a polymerase chain reaction (PCR) test, antigen, or any authorized commercial or public health assay (nasopharyngeal, oropharyngeal, or respiratory samples, not serology testing). Male patients and female patients of childbearing potential must agree to use protocol-specified methods of contraception. Female patients of childbearing potential must have a negative pregnancy test at Screening or pretreatment on Day 1. Male patients must agree not to donate sperm from the first dose through 90 days after the last dose of study treatment; female patients of childbearing potential should refrain from donation of ova from Day 1 until 90 days after the last dose of study treatment. Patient is, in the opinion of the investigator, willing and able to comply with the study treatment regimen and all other study requirements. Exclusion Criteria: Female patient is pregnant or breastfeeding. Any patient's concomitant life threatening condition, including but not limited to: requiring mechanical ventilation, acute respiratory distress syndrome, shock, or cardiac failure. Evidence of multi lobar consolidation pneumonia or cavities on chest x ray or CT scan. Severe COVID 19 disease as defined by the WHO COVID-19 Clinical Improvement Ordinal Scale, scores of 5 (non invasive ventilation or high flow oxygen), 6 (intubation and mechanical ventilation), or 7 (ventilation + additional organ support pressors, renal replacement therapy, ECMO). Medical history significant for the following pulmonary diseases: lung cancer, cystic fibrosis, empyema. Respiratory rate >30 respirations per minute. History of abuse of drugs or alcohol that could interfere with adherence to study requirements, as judged by the investigator. Treatment with other drugs thought to possibly have activity against COVID 19 within 7 days prior to enrollment or concurrently. Note: remdesivir or other authorized treatments for COVID 19 is allowed if considered SoC, if started prior to randomization or during the study. Use of Antrodia camphorata -containing products within 2 weeks prior to the first administration of study drug. Use of other investigational drugs within 30 days of dosing, or plans to enroll in another clinical trial of an investigational agent while participating in the present study. Note: authorized COVID 19 vaccines are not considered investigational and are not exclusionary. Clinically significant abnormal electrocardiogram (ECG) at Screening, as determined by the investigator. 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). Abnormal laboratory values at Screening: Estimated glomerular filtration rate <50 mL/min. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 × upper limit of normal (ULN), or ALT/AST >3 × ULN plus total bilirubin >2 × ULN. Total bilirubin >1.5 × ULN, unless the patient has known Gilbert's syndrome. Hemoglobin <9 g/dL for females or <11 g/dL for males. Absolute neutrophil count <1,500/mm3. Thrombocytopenia (platelets count <100 × 109/L). Treatment with any antiviral drugs (except remdesivir or other authorized treatments for COVID 19), or with any drugs known to be strong inducers or inhibitors of cytochrome P450 isoform (CYP) 2C19, CYP3A4, CYP2C8, and CYP2E1 within 14 days or 5 half lives prior to the start of study treatment. Drugs with a narrow therapeutic index that are substrates of 1A2, 2B6, 2C8, 2C9, 2C19, 3A, and 2D6 are also prohibited. Inability to swallow oral medications or a gastrointestinal disorder with diarrhea (eg, Crohn's disease), malabsorption, or diarrhea of any etiology at baseline. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Interventional Model Description: A Phase 2 Randomized, Double blind, Placebo Controlled, Proof of Concept Study to Evaluate the Safety and Efficacy of Antroquinonol in Hospitalized Patients with Mild to Moderate Pneumonia due to COVID 19
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Antroquinonol with SOC<br>Antroquinonol in a dose of 100 mg (1 capsule) administered twice daily (BID) orally, for 14 days. | Drug: Antroquinonol<br>* double-blind for antroquinonol and Placebo with same out-look and same frequency.<br>* Other names: Hocena;|
| Placebo Comparator: Placebo with SOC<br>Placebo (1 capsule) administered twice daily (BID) orally, for 14 days. | Other: Placebo<br>* Capsule without active compound<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recover Ratio | Number of Patients Who are Alive and Free of Respiratory Failure (e.g., no need for invasive mechanical ventilation, non invasive ventilation, high flow oxygen, or ECMO) on Day 14. | 14 day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to 2-point Improvement, Score 2 or Lower, and Score 0 From Baseline on the WHO COVID-19 Clinical Improvement Ordinal Scale | Time to 2-point improvement from baseline, time to score 2 and lower from baseline and time to score 0 from baseline are measured by WHO COVID-19 Clinical Improvement Ordinal Scale | 28-day | 
| Duration of Hospitalization | Duration of hospitalization is the total number of days the patient is hospitalized during their participation in the study, up to Day 28. | 28 day | 
| Time to Virological Clearance | measured as study days from start of treatment to first negative SARS CoV 2 PCR test | 28 day | 
| Number of Patients Who Recovered From Loss of Taste or Smell | Patients with loss of taste or smell from baseline and back to normal during the observation period. | 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Antroquinonol, COVID 19, pneumonia