Clinical trial NCT04842435: Clinical Study in the Treatment of Patients With Moderate Course of COVID-19
Official title: 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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
PHASE3
Conditions: COVID-19
Keywords: COVID-19
Moderate COVID-19
Pharmacokinetic parameters
Lead sponsor: Microgen
Sponsor class: OTHER
First posted: 2021-04-13
Enrollment: 376
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Stage 1 study will enroll 156 subjects with moderate COVID-19 who will be randomized into the four groups.

Stage 2 will include 220 subjects who will be divided into two groups.
Primary purpose: TREATMENT

Brief summary: Study of safety, efficacy and pharmacokinetics, dose selection

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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
timeFrame: 7 days
Secondary outcomes:
measure: All-cause mortality
timeFrame: 28 days
measure: The elimination time of the SARS-CoV-2 virus
timeFrame: 11 days
measure: The median time to clinical improvement on the WHO Ordinal Scale for Clinical Improvement
timeFrame: 28 days
measure: The incidence of severe and extremely severe COVID-19 disease
timeFrame: 28 days
measure: The need for respiratory support
timeFrame: 28 days
measure: The need for invasive mechanical ventilation of the lungs, ECMO
timeFrame: 28 days
measure: Time to cancellation of oxygen support
timeFrame: 28 days
measure: The need to stay at the intensive care unit
timeFrame: 28 days
measure: Duration of fever (≥ 380C), days
timeFrame: 28 days
measure: The dynamics of the decrease in points on the NEWS scale
timeFrame: 11 days (max. 28 days)
measure: Dynamical CRP, ferritin, D-dimer values
timeFrame: 10 days
measure: Changes in the degree of lung lesion determined by the CT
timeFrame: 7 days
Other outcomes:
Locations:
city: Ekaterinburg
country: Russian Federation
facility: 15. Municipal Autonomous Institution "Central City Clinical Hospital No. 24"
city: Kazan
country: Russian Federation
facility: 9. State Autonomous Healthcare Institution "Professor A. F. Agafonov Republican Clinical Infectious Hospital"
city: Krasnodar
country: Russian Federation
facility: 13. State Budgetary Healthcare Institution "Specialized Clinical Infectious Diseases Hospital" of the Ministry of Health of the Krasnodar Territory
city: Krasnodar
country: Russian Federation
facility: 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
city: Moscow
country: Russian Federation
facility: 1. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 40 of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 14. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 2" of the Moscow Department of Health
city: Moscow
country: Russian Federation
facility: 16. State Budgetary Institution of Healthcare of Moscow "Infectious Clinical Hospital No. 1" of the Moscow Department of Health
city: Moscow
country: Russian Federation
facility: 18. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 52 of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 19. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital of V.P. Demikhova of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 20. State Budgetary Institution of Healthcare of Moscow "Scientific and Research Institute of N.V. Sklifosovskiy of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 21. State Budgetary Institution of Healthcare of Moscow "City Clinical Hospital No. 4 of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 3. State Budgetary Healthcare Institution of Moscow "City Clinical Hospital No. 24 of the Moscow Department of Health"
city: Moscow
country: Russian Federation
facility: 7. Federal State Budgetary Institution "Central Clinical Hospital with an Outpatient Facility" of the Administrative Directorate of the President of the Russian Federation
city: Orenburg
country: Russian Federation
facility: 4. Federal State Budgetary Educational Institution of Higher Education "Orenburg State Medical University" of the Ministry of Health of the Russian Federation
city: Ryazan'
country: Russian Federation
facility: 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
city: Saint Petersburg
country: Russian Federation
facility: 5. Saint Petersburg State Budgetary Healthcare Institution "City Hospital No. 40 of the Kurortny Region"
city: Samara
country: Russian Federation
facility: 12. Federal State Budgetary Educational Institution of Higher Education "Samara State Medical University" of the Ministry of Health of the Russian Federation
city: Smolensk
country: Russian Federation
facility: 11. Regional State Budgetary Healthcare Institution "Clinical Hospital No. 1"
city: Ufa
country: Russian Federation
facility: 17. Federal State Budgetary Educational Institution of Higher Education "Bashkiria State Medical University" of the Ministry of Health of the Russian Federation
city: Yaroslavl
country: Russian Federation
facility: 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"
city: Zhukovskiy
country: Russian Federation
facility: 2. State Budgetary Institution of Healthcare of the Moscow Region "Zhukovskiy City Clinical Hospital"
Study officials:
affiliation: JSC "SIC "Microgen"
name: Ekaterina Andreevna Bykova
role: STUDY_DIRECTOR
References: