The innovative drug Treamid is planned for use in the treatment of patients withpersistent lung damage and reduced exercise tolerance exertion after COVID-19 pneumoniain a multicenter, randomized, double-blind, placebo-controlled Phase IIb/III clinicalstudy to assess the efficacy and safety of Treamid during a 28-day treatment.The primary objective of the study is to prove that in the Treamid group, the proportionof patients achieving clinically significant load tolerance is statisticallysignificantly higher than in the placebo group.The secondary objective of the study is to evaluate the safety of Treamid and achievementof clinically significant improvements in indicators for various questionnaires andspirometry data.
14-18 Russian centers are planned for participation in this study. The study consists of
three periods: screening (2 weeks), treatment period (4 weeks) and follow-up period (4
weeks after completion of treatment with Treamid / Placebo).
412 patients with persistent lung damage and reduced exercise tolerance exertion after
COVID-19 pneumonia are planned to be randomized.
Patients will be evaluated using the Modified British Medical Research Council (mMRC),
six-minute walk test (6-MWT), Borg scale for dyspnea and fatigue, Dyspnea scale Index
(BDI and TDI), KBILD questionnaire, EQ-5D-3L questionnaire, Hospital Anxiety and
Depression Scale (HADS), Modified Fatigue Impact Scale (MFIS), Clinical Global Impression
rating scales (CGI-I and CGI-S), chest computed tomography (CT), spirometry and body
plethysmography with determination of DLCO.
All eligible patients will be randomized into 4 groups of 103 patients each in a 1:1:1:1
ratio: Treamid 25 mg in the morning and Placebo in the evening daily, Treamid 25 mg in
the morning and Treamid 25 mg in the evening daily, Treamid 50 mg in the morning and
Placebo in the evening daily, Placebo in the morning and Placebo in the evening daily.
Patients will visit the study center at the Week 1, Week 2, Week 4 of treatment period
and at the end of the follow up period. During all visits will be evaluated Adverse
events (AEs), concomitant therapy, investigational drug registration, body weight, vital
signs and Oxygen saturation (SpO2) scores. 6-MWT, Borg scale for dyspnea and fatigue,
Dyspnea scale Index (TDI), KBILD questionnaire and MFIS will be also evaluated.
Drug: Treamid
Participants will receive Treamid 25 mg once a day daily during 4 weeks
Drug: Treamid twice a day
Participants will receive Treamid 25 mg in the morning and in the evening daily during 4
weeks
Drug: Treamid once a day
Participants will receive Treamid 50 mg in the morning daily during 4 weeks
Drug: Placebo
Participants will receive Placebo in the morning and in the evening daily during 4 weeks
Inclusion Criteria:
1. Signed patient explanation sheet and informed consent for participation in the
study.
2. Men and women at the age from 18 through 75 years old.
3. History of acute coronavirus infection:
- The patient has a history of confirmed diagnosis of COVID-19 pneumonia, which
resolved more than 2 weeks before screening;
- History of COVID-19 is confirmed by positive qualitative analysis of SARS-CoV-2
by polymerase chain reaction (PCR) or detection of SARS-CoV-2 antigens;
- Negative rapid test for SARS-CoV-2 antigen at screening and randomization;
- Onset of first symptoms of COVID-19 from 42 to 120 days prior to randomization.
4. Severity of mMRC dyspnea ≥2 at screening and randomization.
5. Severity of exercise tolerance impairment at screening and randomization based on
the 6-minute Walk Test:
- reduction of the distance traveled below the normal limit (< 80% of predicted)
at the level of shortness of breath ≥2 units according to the Borg scale;
- severity of shortness of breath > 2 units according to the Borg scale,
regardless of the presence of violations in the distance traveled.
6. The presence of foci of lung tissue seals such as "frosted glass" and/or
interlobular septum seals, and/or areas of reticular changes in lung tissue, and/or
the presence of areas (linear, focal) of lung tissue seals characteristic of
COVID-19 confirmed by chest CT at screening. The percentage of lung tissue damage is
≥10%, but < 75% of the total lung volume.
7. The pulmonary diffusivity parameter is less than 80%, but more than 40% of predicted
at the time of screening.
8. The patient's consent to use adequate contraception methods during the entire study
and within 3 weeks after its completion. The adequate contraception methods include
the use of the following:
- oral or transdermal contraceptives;
- condom or diaphragm (barrier method) with spermicide;
- intrauterine device.
Exclusion Criteria:
1. Hypersensitivity to Treamid (active pharmaceutical substance XC268BG) and/or other
components of the study drug.
2. History of invasive mechanical ventilation and high-flow oxygenation in the last 45
days or need for oxygen support at screening and randomization.
3. Chronic respiratory diseases diagnosed before COVID-19, including idiopathic
pulmonary fibrosis and other interstitial lung diseases, moderate to severe
bronchial asthma, moderate to severe chronic obstructive pulmonary disease,
tuberculosis (including suspected tuberculosis based on CT examination at screening)
or pulmonary hypertension.
4. Severe anemia (Haemoglobin < 70 g/L at screening).
5. Inability to perform a CT procedure (for example, a gypsum bandage or metal
structures in the study area).
6. Severe cardiovascular disease at present or within 6 months prior to screening,
including: Class III or IV chronic heart failure (New York Heart Association
classification), clinically significant ventricular arrhythmias (ventricular
tachycardia, ventricular fibrillation), unstable angina, myocardial infarction,
heart and coronary vessel surgery, significant heart valve disease, uncontrolled
hypertension with systolic blood pressure > 180 mmHg and diastolic blood pressure >
110 mmHg, pulmonary embolism arteries or deep vein thrombosis.
7. Chronic kidney disease or other significant kidney disease with glomerular
filtration rate (GFR) < 60 mL/min (Cockcroft-Gault formula) at screening.
Hemodialysis requirement at patient screening.
8. Stage II chronic liver failure (decompensated) and above; History of liver
cirrhosis; alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST)
elevations of 3 or more times the upper limit of normal (ULN) at screening; increase
in total bilirubin 2 or more times from ULN at screening (exception - Gilbert's
syndrome in the history).
9. Severe diseases of the central nervous system, including a history of seizures or
conditions that may lead to their development; stroke or transient ischemic attack
within 6 months prior to screening; traumatic brain injury or loss of consciousness
within 6 months prior to screening; brain tumor.
10. Malignancies requiring chemotherapy treatment within 5 years prior to screening or
currently suspected cancer.
11. Participation in other clinical trials within 1.5 months prior to screening.
12. Requirement for or administration of the following drugs for 1 month prior to
screening: erythropoietin, cytostatics, colchicine, cyclosporin A, interferon- γ
-1b, bosentan, macitentan, etanercept, sildenafil, imatinib, warfarin, ambrisentan,
nintedanib, pirfenidone, hyaluronidase asoxime 1 month prior to screening;
glucocorticosteroids and N-acetylcysteine (requirement or 7 days prior to screening)
13. Lactase deficiency, lactose intolerance, glucose-galactose malabsorption.
14. Signs of a marked uncontrolled concomitant disease, such as disorders of the nervous
system, kidney, liver, endocrine system and gastrointestinal tract, which, in the
opinion of the Investigator, could prevent the patient from participating in the
study.
15. Positive test for human immunodeficiency virus (HIV), hepatitis B and/or C.
16. Alcohol or drug addiction, history of mental illness.
17. Severe, decompensated or unstable somatic diseases (any diseases or conditions that
threaten the patient's life or impair the patient's prognosis, and make it
impossible for him to participate in a clinical trial).
18. Patient's unwillingness or inability to comply with Protocol procedures (in the
opinion of the study physician).
19. Pregnancy or breastfeeding period.
20. Other conditions that, in the opinion of the study physician, prevent the patient
from entering the study.
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