SARS-CoV-2 Infection
Conditions
Keywords
COVID19, Coronavirus
Brief summary
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.
Detailed description
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.
Interventions
DRUGXC221
Participants will receive XC221 100 mg 2 times a day during 14 days
DRUGPlacebo
Participants will receive Placebo 2 times a day during 14 days
Sponsors
RSV Therapeutics LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
Tablets identical in terms of composition, appearance and labeling to XC221 tablets, but without active substance will be used as Placebo.
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Patient rate with a transition to category 3 or lower according to the WHO scale by Day 14 after the beginning of drug administration. | Day 1 - Day 14 | The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average alteration in CT data by 1 point in terms of severity (CT-1, CT-2, CT-3, CT-4) by Day 7, 10, 15, 18, 21 and 28 compared to the baseline value. | Day 1 - Day 28 | — |
| Time till clinical improvement, which is described by presence of all of the following factors during 48 hours in a row. | Day 1 - Day 28 | * Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; * RR ≤ 22 / min without oxygen therapy; * SpO2 ≥ 95% without oxygen therapy. |
| Patient rate with clinical improvement by day 2-28. Presence of all of the following factors during 48 hours in a row. | Day 1 - Day 28 | * Body temperature ≤ 37.5°C without using NSAIDs and / or paracetamol; * RR ≤ 22 / min without oxygen therapy; * SpO2 ≥ 95% without oxygen therapy. |
| Patient rate with a negative test result for SARS-CoV-2 by Day 7±1, 15±1, 21 ±1 and 28 ± 1. | Day 1 - Day 28 | — |
| Duration of hospitalization. | Day 1 - Day 28 | — |
| Patient rate transferred to the intensive care unit (ICU) during hospitalization. | Day 1 - Day 28 | — |
| Duration of ICU stay. | Day 1 - Day 28 | — |
| Patient rate with ARDS during hospitalization. | Day 1 - Day 28 | — |
| Presence of a fatal outcome. | Day 1 - Day 28 | — |
| Patient rate requiring oxygen therapy by Day 2-28. | Day 1 - Day 28 | — |
| Patient rate requiring high-flow oxygen therapy by Day 2-28. | Day 1 - Day 28 | — |
| Patient rate requiring non-invasive ventilation by Day 2-28. | Day 1 - Day 28 | — |
| Patient rate requiring invasive ventilation by Day 2-28. | Day 1 - Day 28 | — |
| Patient rate requiring extracorporeal membrane oxygenation (EMO) by Day 2-28. | Day 1 - Day 28 | — |
| Average time to reach CT-1 according to CT data. | Day 1 - Day 28 | — |
| The total duration of oxygen therapy by the last day of hospitalization. | Day 1 - Day 28 | — |
| The total duration of high-flow oxygen therapy by the last day of hospitalization. | Day 1 - Day 28 | — |
| The total duration of non-invasive ventilation by the last day of hospitalization. | Day 1 - Day 28 | — |
| The total duration of invasive ventilation of lungs by the last day of hospitalization. | Day 1 - Day 28 | — |
| The total duration of EMO by the last day of hospitalization. | Day 1 - Day 28 | — |
| Patient rate with Sp02 > 95% by Day 2-28. | Day 1 - Day 28 | — |
| Average alteration of Sp02 by Day 2-28 from baseline. | Day 1 - Day 28 | — |
| Average time to reach SpO2 ≥ 95%. | Day 1 - Day 28 | — |
| Patient rate with RR < 22 / min by Day 2-28. | Day 1 - Day 28 | — |
| Average alteration in RR by Day 2-28 from baseline. | Day 1 - Day 28 | — |
| Average time to reach RR ≤ 22 / min. | Day 1 - Day 28 | — |
| Patient rate with body temperature < 37.5°C by Day 2-28. | Day 1 - Day 28 | — |
| Average alteration in body temperature by Day 2-28 from baseline. | Day 1 - Day 28 | — |
| Average time until the patient reaches a body temperature of ≤37.5°C. | Day 1 - Day 28 | — |
| Patient rate with CT-1 according to CT data by Day 2-28. | Day 1 - Day 28 | — |
| Patient rate with a score < 2 according to the Daytime and Nighttime Cough Scale by Day 2-28. | Day 1 - Day 28 | The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible). |
| Mean change in Daytime and Nighttime Cough scores by Day 2-28 from baseline. | Day 1 - Day 28 | The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible). |
| Average time to reach < 2 points when assessed according to the Daytime and Nighttime Cough Scale. | Day 1 - Day 28 | The Daytime and Nighttime Cough Scale will be used to assess the dynamics of cough during the study. Ranges for assess: 0 points (no cough) - 6 points (severe cough that makes daytime activity impossible). |
| Patient rate with a score < 1 for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28. | Day 1 - Day 28 | The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom. |
| Average change in score for each symptom (general fatigue, chest congestion, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale by Day 2-28 from baseline. | Day 1 - Day 28 | The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom. |
| Average time to reach a score of < 1 for each symptom (general fatigue, feeling of congestion in the chest, sore throat, decreased sense of smell and taste, nasal congestion) according to a 4-point scale. | Day 1 - Day 28 | The Symptom Rating Scale will be used to assess the individuals' subjective ratings the severity of 6 symptoms of COVID-19. Ranges for each symptom: 0 points (no symptoms) - 3 points (the most severe). Total score (ranges from 0 to 18 points) is a sum of points for each symptom. |
| Patient rate with a transition decrease to category 3 or lower according to the WHO scale by Day 2-13 and Day 15-28. | Day 1 - Day 28 | The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death). |
| Average time to reach the 3rd category or below according to the WHO scale. | Day 1 - Day 28 | The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death). |
| Patient rate with a NEWS score < 2 by Day 2-28. | Day 1 - Day 28 | Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen. |
| Average change in NEWS score by Day 2-28 from baseline. | Day 1 - Day 28 | Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen. |
| Average time to reach a NEWS score ≤ 2. | Day 1 - Day 28 | Parameters will be assessed according to the National Early Warning Score only during hospitalization. During the treatment period, the assessment will be performed 2 times a day. During the follow-up period, the assessment will be performed once a day. The worst result for each period is to be chosen. |
| Mean WHO grade change by Day 2-28 from baseline. | Day 1 - Day 28 | The scale of the patient's clinical condition, proposed by the WHO, will be used to assess the severity of patient general condition. Ranges for patient's clinical condition: 0 points (no infection) - 8 points (death). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Concentration of IL-6 on Days 3 ± 1, 7 ± 1, 15 ± 1. | Day 1 - Day 15 | (Search Outcome) |
Countries
Russia
Outcome results
None listed