Observational Open Study of Polyoxidonium in Hospitalized Patients With COVID-19

Study Overview
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Brief Summary
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The study is designed as an open observational non-comparative study of Polyoxidonium®, lyophilizate for solution for injections and topical application, 12 mg in hospitalized patients with coronavirus disease (COVID-19).

Detailed Description
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The study was planned as an observation of Polyoxidonium® administered in addition to Russian Ministry of Healthcare (MoH) guidance for standard COVID-19 treatment. Regimens have no limitations to the use of concomitant therapy. The aim of the study is to observe the safety and efficacy of Polyoxidonium®, lyophilizate for solution for injections, 12 mg in addition to complex treatment of hospitalized patients with COVID-19.

Official Title
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Open Observational Study of Efficacy and Safety of Polyoxidonium in Complex Therapy of Hospitalized Patients With COVID-19

Conditions
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Infections, Coronavirus

Intervention / Treatment
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* Drug: Polyoxidonium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The hospitalized patient was administered Polyoxidonium, according to the instruction for medical usage in complex with Russian MoH guidance for treatment of COVID-19. Verified coronavirus disease COVID-19, and at least one of the following: severe disease: mechanical ventilation or oxygen supply required with blood oxygen saturation (SpO2) ≤ 94% on room air or tachypnea, respiratory rate ≥ 24 breaths per minute, mild-moderate disease: SpO2 > 94% on room air or respiratory rate < 24 breaths per minute. The patient signed an Informed Consent form for participation in this study. The patient can understand all protocol requirements, perform the study procedures, and agree to all limitations specified in the protocol. Male and female patients from 18 years of age. Confirmed diagnosis of coronavirus disease (COVID-19): laboratory-confirmed Severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) infection as determined by polymerase chain reaction (PCR), or other commercial or public health assay in any specimen prior to inclusion. Exclusion Criteria: Pregnancy or breastfeeding. Pathological condition that the study doctor considers significant enough to prevent enrolment of this patient. Participation in any clinical study within 30 days before the Informed Consent form provided. Hypersensitivity and/or intolerability to any ingredient of the investigational product. Acute or chronic renal failure.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult patients hospitalized with COVID-19<br>Patients eligible for enrollment into the study | Drug: Polyoxidonium<br>* Polyoxidonium (azoximer bromide) is administered in the dose of 12 mg (contents of 2 vials) once daily intravenously (IV) for 3 days, then every other day intramuscularly (IM) on days 5-17 (the total treatment course is 10 injections)<br>* Other names: azoximer bromide;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Status of the Patient (According to 7-point Ordinal Scale) | Subject clinical status using the 7-point Ordinal Scale, specified as the primary endpoint in the WHO Master Protocol on day 15 as compared to baseline (1 - Not hospitalized, no limitations on activities; 2 - Not hospitalized, limitation on activities; 3 - Hospitalized, not requiring supplemental oxygen; 4 - Hospitalized, requiring supplemental oxygen; 5 - Hospitalized, on non-invasive ventilation or high flow oxygen devices; 6 - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; 7 - Death). | Day 1 (Baseline), Day 15 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to Improvement in Clinical Status of the Patient (According to Ordinal Scale) by 1 Point for Each OS Score | Ordinal scale (OS) score status, time to improvement by 1 point for each OS score. Subject clinical status using the 7-point Ordinal Scale: - Not hospitalized, no limitations on activities; - Not hospitalized, limitation on activities; - Hospitalized, not requiring supplemental oxygen; - Hospitalized, requiring supplemental oxygen; - Hospitalized, on non-invasive ventilation or high flow oxygen devices; - Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation; - Death. | Days 1 - 29. | 
| Clinical Status of the Patient (According to National Early Warning Score (NEWS Scale)) | NEWS scale score status, time to a discharge from a hospital or to a NEWS of ≤ 2 and maintained for 24 hours, whichever occurs first. NEWS score is based on 7 clinical parameters: respiration rate, oxygen saturation, supplemental oxygen, systolic blood pressure, pulse rate, level of consciousness, temperature. A score of 0, 1, 2, 3 is allocated to each parameter except supplemental oxygen (a score 0 or 1 is allocated) and level of consciousness (a score 0 or 3 is allocated). A higher score means the parameter is further from the normal range. All scores were summed to get an aggregate score. Aggregate score ranges from 0 to 19, with higher scores meaning higher risk. Low risk - aggregate score, 1-4 Low to medium risk - score 3 in any single parameter, Medium risk - aggregate score 5-6, High risk - aggregate score 7-19. | Days 1 - 29. | 
| Number of Patients Requiring Supplementary Oxygen | Number of patients requiring supplementary oxygen on Days 3, 5, 8, 11, 15, 29 | Days intervals 1 (baseline), 3, 5, 8, 11, 15, 29. | 
| Hospitalisation Duration | Duration of hospitalisation | Days 1 - 29 | 
| Mortality | Number of participants who were dead or alive (Days 1 - 29) | Days 1 - 29. | 
| The Number of Participants With Serious Adverse Events | The number of participants with serious adverse events (SAE) | Days 1 - 29. | 
| The Number of Participants With Adverse Events | The number of participants with adverse events (AE) | Days 1 - 29. | 
| Number of Participants With Discontinuation of Drug Administration | Number of participants with Permanent or temporary discontinuation of infusions or injections due to adverse events | Days 1 - 17. |