Clinical Study in the Treatment of Patients With Moderate Course of COVID-19

May 12, 2021 updated by: Microgen

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 of safety, efficacy and pharmacokinetics, dose selection

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Anticipated)

376

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Russian Federation
      • Ekaterinburg, Russian Federation
        • Suspended
        • 15. Municipal Autonomous Institution "Central City Clinical Hospital No. 24"
      • Kazan, Russian Federation
        • Recruiting
        • 9. State Autonomous Healthcare Institution "Professor A. F. Agafonov Republican Clinical Infectious Hospital"
        • Contact:
      • Krasnodar, Russian Federation
        • Recruiting
        • 13. State Budgetary Healthcare Institution "Specialized Clinical Infectious Diseases Hospital" of the Ministry of Health of the Krasnodar Territory
        • Contact:
      • Krasnodar, Russian Federation
        • Terminated
        • 6. State Budgetary Healthcare Institution "Scientific and Research Institute Professor S. V. Ochapovskiy Territorial Clinical Hospital" of the Ministry of Health of the Krasnodar Territory
      • Moscow, Russian Federation
        • Recruiting
        • 1. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 40 of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 14. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 2" of the Moscow Department of Health
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 16. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 1" of the Moscow Department of Health
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 18. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 52 of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 19. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital of V.P. Demikhova of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 20. State Budgetary Institution of Healthcare of Moscow "Scientific and Research Institute of N.V. Sklifosovskiy of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 21. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 4 of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Recruiting
        • 3. State Budgetary Healthcare Institution of Moscow "City Clinical Hospital No. 24 of the Moscow Department of Health"
        • Contact:
      • Moscow, Russian Federation
        • Terminated
        • 7. Federal State Budgetary Institution "Central Clinical Hospital with an Outpatient Facility" of the Administrative Directorate of the President of the Russian Federation
      • Orenburg, Russian Federation
        • Recruiting
        • 4. Federal State Budgetary Educational Institution of Higher Education "Orenburg State Medical University" of the Ministry of Health of the Russian Federation
        • Contact:
      • Ryazan', Russian Federation
        • Recruiting
        • 10. Federal State Budgetary Educational Institution of Higher Education "Academician I. P. Pavlov Ryazan State Medical University" of the Ministry of Health of the Russian Federation
        • Contact:
      • Saint Petersburg, Russian Federation
        • Terminated
        • 5. Saint Petersburg State Budgetary Healthcare Institution "City Hospital No. 40 of the Kurortny Region"
      • Samara, Russian Federation
        • Recruiting
        • 12. Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
        • Contact:
      • Smolensk, Russian Federation
        • Recruiting
        • 11. Regional State Budgetary Healthcare Institution "Clinical Hospital No. 1"
        • Contact:
      • Ufa, Russian Federation
        • Suspended
        • 17. Federal State Budgetary Educational Institution of Higher Education "Bashkiria State Medical University" of the Ministry of Health of the Russian Federation
      • Yaroslavl, Russian Federation
        • Suspended
        • 8. State Budgetary Healthcare Institution of the Yaroslavl Region "Yaroslavl Regional Clinical Hospital of War Veterans - International Center for Problems of the Elderly "Zdorovoye Dolgoletiye"
      • Zhukovskiy, Russian Federation
        • Recruiting
        • 2. State Budgetary Institution of Healthcare of the Moscow Region "Zhukovskiy City Clinical Hospital"
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Patients who are able to sign the informed consent form to partic-ipate in the clinical study;
  2. Patients of both sexes at the age of 18-65 years of age;
  3. Positive SARS-CoV-2 RNA test result obtained by PCR during the current episode of COVID-19 disease;
  4. One or more clinical manifestations of ARI (acute respiratory infection) or patient complaints: cough (dry or scanty sputum), edema (including during exercise), chest congestion, sore throat, nasal congestion, or mild rhinorrhea, impairment or loss of smell (hyposmia or anosmia), loss of taste (dysgeusia), conjunctivitis, weakness, muscle pain, headache, vomiting, diarrhea, skin manifestations).

  5. Patients with a moderate course of COVID-19, determined on the basis of at least one of the criteria specified in the Interim Guide-lines of the Ministry of Health (assessed from the moment of mani-festation of the disease symptoms):

    • Body Т > 38 °C
    • RR > 22/min
    • SpO2 < 95 % (at the atmospheric air)
    • CRP of the blood serum > 10 mg/L
  6. CT changes typical of viral lesions (minimal or moderate lesion vol-ume; CT 1-2, no more than 72 hours before screening)
  7. Patients meeting the requirements of the Clinical Study Protocol;
  8. Negative pregnancy test (for women with preserved reproductive potential).

Exclusion Criteria:

  1. A history of allergic reactions to human blood products;
  2. Allergic reactions to the components of the study drug;
  3. Hypersensitivity to human immunoglobulin;
  4. Positive direct Coombs test (antiglobulin test);
  5. Condition requiring invasive oxygen support at Screening;
  6. Subjects with mild, severe, extremely severe COVID-19, as well as those at an outpatient treatment and not scheduled for hospitali-zation;
  7. Administration of blood products or blood derivatives within 3 months prior to enrollment;
  8. Administration of any antiviral, immunomodulatory drugs after the manifestation of COVID-19 (except for those to be prescribed dur-ing the study / included in the standard therapy);
  9. Pathology of the immune system (primary and secondary immu-nodeficiencies, deficiency of class A immunoglobulin (IgA) and / or the presence of IgA antibodies, autoimmune diseases);
  10. Child Pugh class B and C liver cirrhosis;
  11. Diabetes mellitus type 1.
  12. Diseases of the thyroid gland with decompensation.
  13. Signs of severe CNS lesions (past serious brain injury, meningitis, history of ischemic stroke, encephalopathy of various etiologies, epilepsy, etc.);
  14. Serious blood diseases, current or in the history (for example, baseline anemia Hb < 80, myeloid leukemia, myelodysplastic syn-drome, etc.);
  15. The period after the coronary artery bypass grafting / stenting of at least 3 months prior to enrollment;
  16. Malignant neoplasm of any localization at present or within 5 years before enrollment into the study, except for completely healed carcinoma in situ;
  17. Conditions and diseases, other than COVID-19, known from anam-nesis, accompanied by blood hypercoagulability syndrome and a trend for thrombosis (such as sickle cell anemia, polycythemia, hemostatic disorders);
  18. Severe dyslipidemia in the history;
  19. Disseminated intravascular coagulation syndrome, thrombosis and thromboembolism of any localization, known from the history;
  20. CKD-EPI GFR < 30 mL/min at screening;
  21. History of chronic III-IV FC heart failure;
  22. Pregnancy or lactation;
  23. Participation in any other clinical study within the last 3 months;
  24. A history of tuberculosis, cancer or a positive reaction to HIV infec-tion, hepatitis B and C, syphilis according to the history;
  25. Impossibility of intravenous administration of the drug;
  26. Severe visual and/or hearing impairments, severe speech impair-ments and/or other abnormalities that may prevent the patient from adequate cooperation during the study);
  27. Mental diseases in the history;
  28. A history of alcohol, drug or medicinal product abuse;
  29. Patients who, in the opinion of the investigator, are clearly or likely to be unable to understand and evaluate the information on this study within the informed consent signing process, in particular regarding the expected risks and possible discomfort;
  30. Other diseases, symptoms or conditions not listed above that can be an obstacle to participation in a clinical study in the investiga-tor's opinion.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: DOUBLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Stage 1. Group 1
Group 1 - 39 subjects who will receive a single intravenous infusion of COVID-globulin at a dose of 1 mL/kg in addition to standard therapy
Drug: COVID-globulin

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.

Other Names:
  • Anti-coronavirus human immunoglobulin
EXPERIMENTAL: Stage 1. Group 2
Group 2 - 39 subjects who will receive a single intravenous infusion of COVID-globulin at a dose of 2 mL/kg in addition to standard therapy
Drug: COVID-globulin

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.

Other Names:
  • Anti-coronavirus human immunoglobulin
EXPERIMENTAL: Stage 1. Group 3
Group 3 - 39 subjects who will receive a single intravenous infusion of COVID-globulin at a dose of 4 mL/kg in addition to standard therapy
Drug: COVID-globulin

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.

Other Names:
  • Anti-coronavirus human immunoglobulin
PLACEBO_COMPARATOR: Stage 1. Group 4
Group 4 - 39 subjects who will receive a single intravenous infusion of placebo at a dose of 1 mL/kg in addition to standard therapy
Drug: Placebo

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.

Other Names:
  • 0.9% NaCl solution
ACTIVE_COMPARATOR: Stage 2. Group 1
Group 1 - 110 subjects who will receive a single intravenous infusion of COVID-globulin at a dose defined at Stage 1 in addition to standard therapy
Drug: COVID-globulin

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.

Other Names:
  • Anti-coronavirus human immunoglobulin
PLACEBO_COMPARATOR: Stage 2. Group 2
Group 2 - 110 subjects who will receive a single intravenous infusion of placebo at a dose equal to the COVID-globulin dose in addition to standard therapy
Drug: Placebo

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.

Other Names:
  • 0.9% NaCl solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 7 days

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)
7 days

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-cause mortality
Time Frame: 28 days
All-cause mortality (follow-up period of 28 days after the treatment initiation).
28 days
The elimination time of the SARS-CoV-2 virus
Time Frame: 11 days
The elimination time of the SARS-CoV-2 virus from the upper respiratory tract (follow-up period of 11 days after the treatment initiation).
11 days
The median time to clinical improvement on the WHO Ordinal Scale for Clinical Improvement
Time Frame: 28 days
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.
28 days
The incidence of severe and extremely severe COVID-19 disease
Time Frame: 28 days
The incidence of severe and extremely severe COVID-19 disease (follow-up period of 28 days after the treatment initiation).
28 days
The need for respiratory support
Time Frame: 28 days
The need for respiratory support (follow-up period of 28 days after the treatment initiation).
28 days
The need for invasive mechanical ventilation of the lungs, ECMO
Time Frame: 28 days
The need for invasive mechanical ventilation of the lungs, ECMO (follow-up period of 28 days after the treatment initiation).
28 days
Time to cancellation of oxygen support
Time Frame: 28 days
Time to cancellation of oxygen support, if any, days (follow-up period of 28 days after the treatment initiation).
28 days
The need to stay at the intensive care unit
Time Frame: 28 days
The need to stay at the intensive care unit (follow-up period of 28 days after the treatment initiation).
28 days
Duration of fever (≥ 380C), days
Time Frame: 28 days
Duration of fever (≥ 380C), days (follow-up period of 28 days after the treatment initiation).
28 days
The dynamics of the decrease in points on the NEWS scale
Time Frame: 11 days (max. 28 days)

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.
11 days (max. 28 days)
Dynamical CRP, ferritin, D-dimer values
Time Frame: 10 days

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.
10 days
Changes in the degree of lung lesion determined by the CT
Time Frame: 7 days
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).
7 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Microgen

Investigators

  • Study Director: Ekaterina Andreevna Bykova, JSC "SIC "Microgen"

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 12, 2021

Primary Completion (ANTICIPATED)

September 30, 2021

Study Completion (ANTICIPATED)

October 5, 2021

Study Registration Dates

First Submitted

April 12, 2021

First Submitted That Met QC Criteria

April 12, 2021

First Posted (ACTUAL)

April 13, 2021

Study Record Updates

Last Update Posted (ACTUAL)

May 14, 2021

Last Update Submitted That Met QC Criteria

May 12, 2021

Last Verified

May 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IGK-P-II/III-00-003/2020

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

All of the individual participant data collected during the trial, after deidentification

IPD Sharing Time Frame

Immediately following publication. No end date

IPD Sharing Access Criteria

Anyone who wishes to access the data

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF
  • ANALYTIC_CODE
  • CSR

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on COVID-19

Clinical Trials on COVID-globulin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Malta

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe