Study of safety, efficacy and pharmacokinetics, dose selection
Objective: To study the efficacy, safety and pharmacokinetics of COVID-globulin, in addition to standard therapy for the treatment of patients with a moderate COVID-19 form. Study Objectives: The study comprises two stages, 1 and 2. Stage 1 tasks 1. to determine and compare the safety parameters of COVID-globulin after a single infusion at doses of 1 mL/kg, 2 mL/kg, 4 mL/kg and placebo in addition to standard therapy in the treatment of patients with COVID-19; 2. to determine and compare the efficacy parameters of COVID-globulin after a single infusion at doses of 1 mL/kg, 2 mL/kg, 4 mL/kg and placebo in addition to standard therapy in the treatment of patients with COVID-19; 3. to determine the optimal therapeutic dose of COVID-globulin for the treatment of patients with moderate COVID-19 by comparing the safety and efficacy parameters of doses of 1 mL/kg, 2 mL/kg, 4 mL/kg and placebo; 4. to study the pharmacokinetic parameters of COVID-globulin in the blood plasma of patients after a single infusion at a dose of 1 mL/kg, 2 mL/kg, 4 mL/kg, in addition to standard therapy for the treatment of patients with moderate COVID-19. Stage 2 tasks 1. to study the efficacy of COVID-globulin in addition to standard therapy for the treatment of patients with moderate COVID-19; 2. to study the safety of COVID-globulin in addition to standard therapy for the treatment of patients with moderate COVID-19; 3. to conduct a comparative analysis of the efficacy and safety of a group of patients with moderate COVID-19 who receive COVID-globulin in addition to the standard therapy, and a group of patients who receive placebo in addition to standard therapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
376
In a Stage 1 study, COVID globulin is administered to clinical study subjects randomized to groups 1, 2, or 3 by intravenous drip in one of three doses of 1 mL/kg, 2 mL/kg, or 4 mL/kg The initial drug administration rate is from 0.01 mL/kg to 0.02 mL/kg of body weight per minute for 30 minutes. If the drug is well tolerated, the rate of administration can be gradually increased to a maximum of 0.12 mL/kg of body weight per minute. In order to control the drug administration rate, infusion shall be performed with an infusion pump. In a Stage 2 study, COVID globulin is administered to clinical study subjects randomized to group 1 by intravenous drip at a dose found optimal based on the results of Stage 1 study.
In a Stage 1 study, Placebo is administered to clinical study subjects randomized to groups 4 by intravenous drip at a dose of 1 mL/kg. The initial drug administration rate is from 0.01 mL/kg to 0.02 mL/kg of body weight per minute for 30 minutes. If the drug is well tolerated, the rate of administration can be gradually increased to a maximum of 0.12 mL/kg of body weight per minute. In order to control the drug administration rate, infusion shall be performed with an infusion pump. In a Stage 2 study, placebo is administered to clinical study subjects randomized to group 2 by intravenous drip at a dose equal to the study drug dose.
The proportion of subjects in the study groups in whom, during the first 7 days after drug administration, one of the following events developed according to the laboratory-instrumental methods or on the basis of a clinical presentation
Laboratory-instrumental methods or on the basis of a clinical presentation: * development of acute renal injury stage 2 or higher, assessed by the AKIN (Acute Kidney Injury Network) scale; * development of myocardial dysfunction or acute coronary pathology; * development of thrombolytic complications; * development of a cytokine storm; * development of an acute respiratory distress syndrome (ARDS); * an increase in the degree of lung lesion, as determined by the CT; * negative dynamics of CRP with an increase in the indicator by more than 30 % compared to the baseline value; * an increase in the D-dimer indicator by more than 2 times compared with the corresponding indicator at the time of hospitalization; * aggravation of clinical symptoms, as determined by the WHO Ordinal Scale, compared with the baseline value. (Aggravation refers to a decrease in a WHO score by 1 point or more as compared to the value at Visit 1)
Time frame: 7 days
All-cause mortality
All-cause mortality (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
The elimination time of the SARS-CoV-2 virus
The elimination time of the SARS-CoV-2 virus from the upper respiratory tract (follow-up period of 11 days after the treatment initiation).
Time frame: 11 days
The median time to clinical improvement on the WHO Ordinal Scale for Clinical Improvement
The median time to clinical improvement on the WHO Ordinal Scale for Clinical Improvement (follow-up period of 28 days after the treatment initiation) using the Hazard Ratio score.
Time frame: 28 days
The incidence of severe and extremely severe COVID-19 disease
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9. State Autonomous Healthcare Institution "Professor A. F. Agafonov Republican Clinical Infectious Hospital"
Kazan', Russia
RECRUITING13. State Budgetary Healthcare Institution "Specialized Clinical Infectious Diseases Hospital" of the Ministry of Health of the Krasnodar Territory
Krasnodar, Russia
RECRUITING6. State Budgetary Healthcare Institution "Scientific and Research Institute Professor S. V. Ochapovskiy Territorial Clinical Hospital" of the Ministry of Health of the Krasnodar Territory
Krasnodar, Russia
TERMINATED1. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 40 of the Moscow Department of Health"
Moscow, Russia
RECRUITING14. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 2" of the Moscow Department of Health
Moscow, Russia
RECRUITING16. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 1" of the Moscow Department of Health
Moscow, Russia
RECRUITING18. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 52 of the Moscow Department of Health"
Moscow, Russia
RECRUITING19. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital of V.P. Demikhova of the Moscow Department of Health"
Moscow, Russia
RECRUITING20. State Budgetary Institution of Healthcare of Moscow "Scientific and Research Institute of N.V. Sklifosovskiy of the Moscow Department of Health"
Moscow, Russia
RECRUITING21. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 4 of the Moscow Department of Health"
Moscow, Russia
RECRUITING...and 11 more locations
The incidence of severe and extremely severe COVID-19 disease (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
The need for respiratory support
The need for respiratory support (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
The need for invasive mechanical ventilation of the lungs, ECMO
The need for invasive mechanical ventilation of the lungs, ECMO (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
Time to cancellation of oxygen support
Time to cancellation of oxygen support, if any, days (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
The need to stay at the intensive care unit
The need to stay at the intensive care unit (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
Duration of fever (≥ 380C), days
Duration of fever (≥ 380C), days (follow-up period of 28 days after the treatment initiation).
Time frame: 28 days
The dynamics of the decrease in points on the NEWS scale
The dynamics of the decrease in points on the NEWS scale. NEWS uses six physiological measurements: respiratory rate; oxygen saturation; temperature; systolic blood pressure; heart rate and level of consciousness. Each scores 0-3 and individual scores are added together for an overall score. An additional one points are added if the patient is receiving oxygen therapy. Higher scores mean a worse outcome.
Time frame: 11 days (max. 28 days)
Dynamical CRP, ferritin, D-dimer values
Dynamical CRP, ferritin, D-dimer values. Local laboratories of research centers will be used for laboratory tests and assessments. After collecting and verification 100% values of laboratory parameters according to the Protocol from all local laboratories, the units of measurement will be unified before Statistical process control by valid formulas for transitions.
Time frame: 10 days
Changes in the degree of lung lesion determined by the CT
Changes in the degree of lung lesion determined by the CT (the result is assessed on the 7th day before the subject is discharged from the hospital compared to the baseline).
Time frame: 7 days