A Study to Assess the Efficacy and Safety of XC221 in Patients With COVID-19

A Multicenter, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of XC221, Tablets, 100 mg in Patients With COVID-19

The innovative drug XC221 100 mg tablet is designed for the treatment of COVID-19 (SARS-CoV-2 infection). A multicenter, adaptive, randomized, double-blind, placebo-controlled Phase III clinical study is aimed to assess the efficacy and safety of XC221 100 mg tablet, in COVID-19 patients during a 14-day treatment.

The primary objective of the study is to demonstrate the efficacy of XC221 100 mg tablet (200 mg daily dose) in achieving clinical improvement of COVID-19 symptoms.

The secondary objective of the study is to evaluate the safety of XC221 100 mg tablet (200 mg daily dose) in COVID-19 patients.

11 Russian centers will participate in this study. The trail will consist of three periods: screening (duration not more than 1 day, it may coincide with the randomization visit and beginning of drug administration), treatment period (14 days) and follow-up period (14 ± 1 days after completion of treatment with XC221 / Placebo). The duration of participation in the study for each patient will be no more than 30 days.

118 eligible patients with confirmed COVID-19 will be randomized into two groups (Group A and Group B) in a 1:1 ratio: Group A - XC221 200 mg daily (59 patients); Group В - Placebo (59 patients).

During the treatment period (14 days), 1 tablet of XC221 / Placebo will be administered 2 times a day in addition to the standard of care (SoC) for COVID-19 according to The Temporary guidelines for the prevention, diagnosis and treatment of SARS-CoV-2 infection of the Ministry of Health of the Russian Federation (the MoH Temporary Guidelines). The follow-up period will last for 14 days.

Inclusion Criteria:

1. Signed Informed Consent Form.

2. Patients of both sexes aged 18 to 75 years inclusive.

3. Diagnosed COVID-19 based on:

   • positive laboratory tests confirming the SARS-CoV-2 presence, performed no earlier than 14 days before hospitalization. It is allowed to determine the SARS-CoV-2 by the PCR or by another method according to the MoH Temporary Guidelines; and / or
   • bilateral alterations in lungs, typical for COVID-19, according to CT scan of the chest.

4. Patients with moderate or severe form of disease (t > 38.0°C; respiratory rate (RR) >22 / min; Sp02 <95%) not requiring non-invasive / invasive ventilation and / or high-flow oxygenation (HFNT), and / or extracorporeal membrane oxygenation (EMO) at the time of screening and randomization (based on the MoH Temporary Guidelines).

5. Patients requiring oxygen therapy (oxygenation through a nasal cannula, a simple facemask or other similar oxygen delivery device) with a category "4" according to the WHO scale.

6. Time from hospitalization to the first drug administration should not exceed 48 hours. This item is to be assessed only when re-evaluating the inclusion / exclusion criteria at the Randomization visit and treatment initiation.

7. Disease duration is no more than 7 full days since the moment of appearing one or more of the symptoms below until the first dose of the drug administration:

   • temperature increase;
   • dry cough or cough with little phlegm;
   • shortness of breath;
   • myalgia;
   • fatigue;
   • feeling of congestion in the chest;
   • reduced sense of smell and / or taste.

8. For women only: negative pregnancy test result. Pregnancy testing is not required for women of not childbearing potential (WONCBP): women who are in menopause (defined as an absence of menstruation for at least 2 years or more), or women who undergone surgical sterilization (hysterectomy, bilateral oophorectomy, tubal ligation), or women with a clinical diagnosis of "infertility". The presence of surgical sterilization and infertility should be confirmed by patient's claim or by relevant document confirming this condition.

9. Consent to use reliable method of contraception throughout the study period.

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

Exclusion Criteria:

1. Known or suspected hypersensitivity to the active substance or to excipients of the drug XC221 or placebo
2. Known or suspected hypersensitivity to standard therapy drugs specified in The MoH Temporary Guidelines.
3. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
4. Presence or suspicion of oncological diseases by the day of criteria assessment or in medical history (within the last 2 years).
5. Presence of autoimmune diseases by the day of criteria assessment or in medical history.
6. Neutropenia (0.5 * 10^9 /l).
7. Exceeding the upper limit of normal for ALT and AST by 5 times or more.
8. Thrombocytopenia 50000 / mm^3.
9. Pregnancy.
10. Lactation.
11. Presence of serious lung diseases, including, but not limited to the following diseases: moderate and severe bronchial asthma, severe and extremely severe COPD, interstitial lung disease, pulmonary hypertension, pulmonary fibrosis, surgical interventions on the lungs, tuberculosis (including suspicion of tuberculosis based on the results of CT examination at screening).
12. Patients with type 1 diabetes mellitus and / or decompensated type 2 diabetes mellitus.
13. Heart failure, NYHA functional class III - IV.
14. Chronic liver failure stage II (decompensated) and higher.
15. The need of renal replacement therapy at the time of inclusion of the patient.
16. Organ transplantation in medical history.
17. Medical history of epilepsy or the need for anticonvulsant therapy.
18. Major depressive disorder, anxiety, other mental disorders requiring medical correction.
19. Acute cerebrovascular accident, stroke or transient ischemic attack within 90 days before screening.
20. Administration of any antiviral and / or immunomodulatory drugs after the manifestation of COVID-19, with the exception of those specified in the MoH Temporary Guidelines.
21. Any immunosuppressive therapy (including tocilizumab / sarilumab) within 90 days prior to randomization, or the need of immunosuppressive therapy at the time of randomization.
22. Administration of systemic glucocorticosteroids within 90 days prior to randomization, or the need of systemic glucocorticosteroids at the time of randomization.
23. Administration of vaccines against viral infections within 90 days prior to randomization.
24. Patients receiving other experimental drugs, drugs not approved in the Russian Federation, or participating in other clinical trials within 30 days before screening.
25. Patients abusing alcohol or psychotropic drugs and other drugs by the day of criteria assessment or during the last year.
26. Patients with other serious, unstable, or clinically significant medical or psychological conditions that, in the opinion of the investigator, may preclude the patient's participation in the study.
27. Expected death within 48 hours after randomization.
28. Expected hospital discharge within 48 hours of randomization.