Efficacy and Safety of Ergoferon for COVID-19 Prevention During Vaccination Against SARS-CoV-2

Design: the multicenter, double-blind, placebo-controlled, parallel-group, randomized trial.

The study will enroll adult participants of either gender aged ≥18 years who receive a COVID-19 vaccine. The participant signs an information sheet (Informed Consent Form) for participation in the clinical study on the day of administration of component I of the Gam-COVID-Vac (Sputnik-V) vaccine. The physician evaluates if the participant is eligible for the study. A SARS-CoV-2 rapid test (BIOCREDIT COVID-19 Ag) is carried out. If the participant tests positive for SARS-CoV-2, he/she is not enrolled in the study. The investigator's approach should be in compliance with the current version of the guidelines "Prevention, diagnosis, and treatment of a new coronavirus infection (COVID-19)" by the Ministry of Health of the Russian Federation.

If the participant meets all inclusion criteria and does not have any exclusion criteria, then he/she is included in the study, and the physician fills in source medical documentation.

Following enrollment in the study (Day 1, Visit 1), the participant is randomized into one of two groups: participants of the Group 1 receive Ergoferon in the preventive regimen for 3 weeks, and participants of the Group 2 receive Placebo in the same regimen for 3 weeks.

On the day of administration of component II of the Gam-COVID-Vac vaccine (day 22, Visit 2 + 3 days) the express test for SARS-CoV-2 (BIOCREDIT COVID-19 Ag) is performed.

After the component II of the vaccine has been administered, the participant is followed up for 2 weeks. After 2 weeks, Visit 3 ("phone visit") is carried out in order to interview the participant about the health status (absence/presence of any ARVI symptoms).

All participants are provided with classic thermometers for measuring axillary temperature. Electronic diaries are used in the trial to record any potential deterioration in the participant's condition (if applicable) for the assessment of efficacy, safety, and registration of adverse events. The investigator trains the participant how to fill in the diary. Once a week, the participant receives an SMS reminder: "If you have symptoms of the disease, note them in your diary. The investigator will contact you".

If the participant develops symptoms of an acute respiratory viral infection (ARVI)? including an increase in body temperature to febrile/subfebrile values, weakness, headache, chills, cough, sore throat, other symptoms, etc. within five weeks of the observation, the investigator will perform an unscheduled visit to collect nasopharynx and oropharynx swabs for the RT-PCR test (performing in the central laboratory).

If the participant without ARVI symptoms will have a positive test for SARS-CoV-2 (rapid test) at Visit 1 or 2, his/her nasal and oropharyngeal swabs will also be collected for RT-PCR testing in the central laboratory.

If a laboratory-confirmed SARS-CoV-2 infection (with or without symptoms) is detected, the participant will complete the participation in the trial as meeting the primary endpoint.

In case of a positive PCR for SARS-CoV-2, in accordance with the requirements of Rospotrebnadzor Agency, the information about it should be transferred to the medical facility where the participant is registered and where appropriate medical care will be provided for the participant in accordance with the current standards. The employees of the medical facility will report COVID-19 data in compliance with the requirements of the Ministry of Health of the Russian Federation and the rules of the medical facility.

Possible post-vaccination symptoms;

• general (a flu-like syndrome characterized by chills, fever, arthralgia, myalgia, asthenia, general malaise, headache) and local (pain at the injection site, hyperemia, swelling) reactions that develop on the first-second day and resolve within three subsequent days;
• nausea, dyspepsia, loss of appetite;
• enlarged regional lymph nodes;
• allergic reactions;
• short-term increase in serum levels of liver transaminases, creatinine, and creatine phosphokinase.

These post-vaccination symptoms are not recorded as adverse events (either associated with the investigational product administration or developing after discontinuation); they are registered by the participant in the diary and assessed by the physician as post-vaccination complications.

The short-term flu-like syndrome should not be diagnosed as ARVI, in this case, the RT-PCR test for SARS-CoV-2 is not performed.

If the participant is ill with COVID-19 or has been hospitalized for COVID-19, a delayed "phone" visit is performed. The visit is scheduled by the investigator depending on each case.

During the study participants are allowed to take medications for their chronic conditions, except for medicines listed as "Prohibited concomitant treatment".

Inclusion criteria

• Adults of either gender aged ≥18 years.
• Participant has not had COVID-19 in the previous 6 months.
• The participant has not been vaccinated against COVID-19 or other viral infections in the previous 6 months.
• Negative rapid test result for SARS-CoV-2 (COVID-19 Ag).
• Absence of clinical manifestations of any infectious disease, but not earlier than 14 days from its onset.
• Consent to use reliable contraceptive methods during the study (for men and women with reproductive potential).
• Presence of a signed information sheet and informed consent form for participation in a clinical trial.

Exclusion criteria

• The presence of contraindications to vaccination:

• hypersensitivity to any component of the vaccine or a vaccine containing similar components;
• prior history of severe allergic reactions;
• acute infectious and non-infectious diseases, exacerbation of chronic diseases.
• Severe chronic hepatic and renal disorders, severe thyroid dysfunction, decompensated diabetes mellitus, severe disorders of the hematopoietic system, epilepsy and other CNS diseases, acute coronary syndrome, acute cerebrovascular accident, myocarditis, endocarditis, pericarditis, autoimmune diseases, or immunodeficiency.
• Malabsorption syndrome, including congenital or acquired lactase deficiency or any other disaccharidase deficiency, galactosemia.
• Hypersensitivity to any of the components of study drug used in the treatment.
• Pregnancy, breast-feeding, childbirth less than 3 months before study enrollment.
• Participants who, from the investigator's point of view, will not comply with study observation requirements or study drug administration procedures.
• Inability to observe the participant during the study period.
• Prior history of mental illness, alcoholism or drug abuse, that the investigator's opinion, will interfere with successful study procedures.
• Participation in other clinical studies within 3 months prior to enrollment in the study.
• Use of any medications listed in "Prohibited concomitant treatment" within 4 weeks before enrollment.
• Participants who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. "Immediate relative" means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted).
• Participants who work for OOO "NPF "MATERIA MEDICA HOLDING" (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).