A Study to Evaluate the Safety, Tolerability and Efficacy of XC221 in Patients With Uncomplicated Influenza or Other Acute Viral Upper Respiratory Infections

A Multicenter, Randomized, Double-blind, Placebo-сontrolled Comparative Study to Evaluate the Safety, Tolerability and Efficacy of XC221 Used at 100 mg Daily and at 200 mg Daily in Patients With Uncomplicated Influenza or Other Acute Viral Upper Respiratory Infections

A multicenter, randomized, double-blind, placebo controlled comparative study to evaluate the safety, tolerability and efficacy of XC221 used at 100 mg daily and at 200 mg daily in patients with uncomplicated influenza or other acute viral upper respiratory infections (URIs) for 5 days of treatment.

The primary objective of the study is to evaluate the efficacy of ХС221 at 100 mg and at 200 mg in comparison with placebo regarding its effect on the severity and duration of influenza symptoms and symptoms of other viral URIs (fever and other major signs and symptoms).

The secondary objective of the study is to evaluate the safety of ХС221 at 100 mg and at 200 mg in comparison with placebo in the treatment of influenza ad other viral URIs.

Russian centers will participate in this study. This is a double-blind, placebo-control study, and therefore, in order to maintain the study design, subjects will be administered with placebo or the study drug depending on the treatment group they have been randomized into.

The screening visit and all other visits of the study will be on an outpatient basis (including home visits). The study will consist of three periods: screening, randomization and initiation of treatment ( Day 1); treatment period (Day 1-5) and follow-up period (Day 6-20± 1 after completion of treatment with XC221 / Placebo). The duration of participation in the study for each patient will be no more than 21 days.

255 eligible patients will be randomized into three treatment groups (in a 1:1:1 ratio) and receive: study drug (ХС221) at 100 mg daily or at 200 mg daily, or placebo. Regardless other group, all study subjects should receive the standard symptomatic therapy for influenza and other viral URIs, taking into account the latest clinical guidelines (the necessity of symptomatic therapy will be decided by the Investigator).

Group 1: subjects will receive 1 tablet of XC221, 100 mg tablets orally in the morning (between 7:00 and 11:00) and 1 tablet of placebo in the evening (between 19:00 and 23:00) regardless of food intake for 5 days.

Group 2: subjects will receive 1 tablet of XC221, 100 mg tablets orally twice daily in the morning (between 7:00 and 11:00) and in the evening (between 19:00 and 23:00) regardless of food intake for 5 days.

Group 3: subjects will receive 1 tablet of placebo orally twice daily, in the morning (between 7:00 and 11:00) and in the evening (between 19:00 and 23:00) regardless of food intake for 5 days.

Inclusion Criteria:

1. Men and women aged 18 to 65 years (inclusive);

2. Signed Informed Consent Form;

3. Clinical symptoms of mild to moderate influenza and other viral URIs:

   • an increased axillary temperature of ≥38.0°С ≤39.5°С during the current illness without the use of antipyretics in the last 8 hours at the time of screening;
   • at least one of the respiratory signs and symptoms of influenza or other viral URIs (cough, runny nose/nasal congestion, sore throat) scored at least 2 points on a 4-point scale;
   • at least one of the systemic signs and symptoms of influenza or other viral URIs (headaches, muscle aches, chills/sweats, fatigue) scored at least 2 points on a 4-point scale.

4. Absence of indications for hospitalization at the time of enrollment;

5. Duration of illness from symptom manifestation to the first drug dose/placebo no more than 48 h;

6. Negative pregnancy test for women of childbearing potential;

7. A consent to use adequate birth control methods throughout the treatment and for 30 days thereafter;

8. Patients who are able to understand and comply with treatment and procedures during the study.

Exclusion Criteria:

1. Pregnant and lactating women;
2. Known or suspected hypersensitivity to the active substance or to excipients of the drug XC221 or placebo;
3. An established or currently suspected diagnosis (based on the assessment of the patient's health and epidemiological medical history) of COVID-19;
4. Oxygen saturation (SpO2) ≤ 95%, respiration rate (RR) ≥ 22/min.
5. Complications of influenza or other viral URIs;
6. Participation in another clinical trial within 90 days prior to screening;
7. Known (based on the medical history) or suspected abuse of alcohol or psychotropic drugs;
8. Patients with psychotic diseases, including in the medical history;
9. Moderate viral URI (fever ≥ 38.5°С) accompanied by exacerbation of concomitant conditions;
10. Clinically suspected pneumonia or other bacterial infections (including sinusitis, otitis media, urinary tract infection, meningitis, sepsis, etc.) requiring antibacterial therapy;
11. Taking antibiotics, antivirals, or immunomodulatory drugs within < 48 h prior to treatment initiation and/or planning to use these types of drugs (except for the investigational products) during the study;
12. Use of systemic, inhaled or nasal corticosteroids within 30 days prior to treatment initiation and/or planning to use corticosteroids (except for topical dermatological agents) during the study;
13. The inability to cancel during the study period other drugs that can affect the result of this study, for example, antiviral drugs, or drugs that are incompatible with the study's therapy;
14. Any diseases of cardiac, renal, hepatic, gastrointestinal, endocrine and nervous system, severe decompensated chronic (including chronic renal and liver diseases) or acute diseases, or any other conditions/diseases which would make participation in the study unsafe (in the investigator's opinion);
15. Patients receiving any vaccines within 90 days prior to enrollment;
16. Diabetes mellitus, grade 2-3 obesity;
17. Patients who underwent surgery within 30 days prior to the screening and patients who are scheduled to undergo surgery during the study period, including diagnostic procedures or hospital stay;
18. Patients with oncological diseases, HIV infection, or tuberculosis, including a medical history;
19. Meningeal syndrome;
20. Disorders of consciousness (in the form of stupor, sopor, delusion, delirium, etc.);
21. Symptoms of pneumonia and possible acute respiratory distress syndrome (ARDS): cough with bloody frothy sputum, shortening of pulmonary sound with percussion, a large number of different-sized wet wheezing and profuse crepitus on auscultation, a sharp decrease in blood pressure (BP), deafness of heart sounds and arrhythmia;
22. Positive rapid test result for SARS-CoV-2;
23. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
24. Other reasons which would prevent the patient from participating in the study and make an unreasonable risk (in the investigator's opinion).