The innovative drug Treamid is planned for use in the rehabilitation of patients after COVID-19 pneumonia in a pilot, multicenter, randomized, double-blind, placebo-controlled Phase II clinical study to assess the efficacy and safety of Treamid, tablets, 50 mg in patients with fibrotic changes in the lungs after COVID-19 pneumonia during a 28-day treatment. The primary objective of the study is to demonstrate the efficacy of Treamid tablet, 50 mg in change in forced vital capacity (FVC) and/or diffusing capacity of lung for carbon monoxide (DLCO) at Week 4. The secondary objective of the study is to evaluate the safety of Treamid tablet, 50 mg and pharmacokinetics (PK).
12-15 Russian centers are planned for participation in this pilot study. The study consists of three periods: screening (2 weeks), treatment period (4 weeks) and follow-up period (2 weeks after completion of treatment with Treamid / Placebo). The duration of participation in the study for each patient is no more than 8 weeks. 60 patients with fibrotic changes in the lungs after COVID-19 pneumonia are planned to be randomized. All patients will undergo a qualitative determination of coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by polymerase chain reaction (PCR). Patients will be evaluated using the Modified British Medical Research Council (mMRC) Dyspnea Scale, chest computed tomography (CT), spirometry and body plethysmography with determination of DLCO. This examination should be conducted as close as possible to the expected randomization date (no earlier than 5 days before). All eligible patients will be randomized into 2 groups in a 1:1 ratio: Treamid 50 mg daily (30 patients); Placebo (30 patients). During the treatment period (4 weeks), patients will receive 1 tablet Treamid / Placebo once a day. Patients will be advised to continue the standard program of medical rehabilitation under day inpatient or outpatient conditions (stage 3 according to the Interim Guidelines for Medical Rehabilitation after New Coronavirus Infection (COVID-19), 2020. Patients will visit the study center once a week. At the Week 1, Week 2 and Week 3 visits, Adverse events (AEs) and concomitant therapy, investigational drug registration, body weight, vital signs and Oxygen saturation (SpO2) scores, mMRC dyspnea score and spirometry will be recorded. During the Week 2 visit, physical examination, electrocardiography (ECG), complete blood count (CBC) and biochemical blood test, PK study, common urine analysis, bodyplethysmography with DLCO will also be conducted. Patients will complete the KBILD questionnaire. Also, the patients will undergo a 6-minute walk test to measure the distance the patient walks for 6 minutes and evaluate using the Borg Scale. At the Week 4 visit (the end of the therapy), registration of AEs and concomitant therapy, physical examination, measurement of height, body weight, vital signs and SpO2, ECG, CBC and biochemical blood tests, PK study and common urine analysis will be conducted. Patients will be evaluated using the mMRC Dyspnea Scale, chest CT, spirometry and body plethysmography with determination of DLCO. Patients will complete the King's Brief Interstitial Lung Disease Questionnaire (KBILD) followed by a 6-minute walk test to measure the distance the patient walks for 6 minutes and evaluate using the Borg Scale. Patient follow-up will continue for another 2 weeks. At the Week 6 visit, registration of AEs and concomitant therapy, physical examination, measurement of height, body weight, vital signs and SpO2, ECG, mMRC dyspnea score, CBC and biochemical blood tests, and common urine analysis will be conducted.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
60
Federal State-Funded Research Institution "Research Institute of Complex Cardiovascular Diseases"
Kemerovo, Russia
Federal State Budgetary Institution "N.N. Burdenko Military Clinical Hospital"
Moscow, Russia
SBEI HPE The First Moscow State Medical University n.a. Sechenov of Ministry of Health of Russian Federation, University Hospital #2, Department of Development of New Medicines
Moscow, Russia
Moscow State Medical-Dentist University n.a. A.I. Evdokimov on basis of SMHI "City Hospital № 62", branch 5
Moscow, Russia
State Budgetary Health Institution "Republican Hospital named V.A.Baranov"
Petrozavodsk, Russia
Federal State Budgetary Educational Institution of Higher Education "Rostov State Medical University"
Rostov-on-Don, Russia
LLC "Medical Center "Reavita Med St. Petersburg"
Saint Petersburg, Russia
State autonomous healthcare institution of Yaroslavl Region "Сlinical hospital for emergency medical care n. a. N.V. Solovyov"
Yaroslavl, Russia
Rate of clinically significant change in FVC and/or DLCO at Week 4 relative to the baseline value
Clinically significant changes include a relative ≥ 10% increase in FVC or a relative increase in FVC within the range from ≥ 5% to \<10% and a relative ≥ 15% in DLCO
Time frame: Day 1- Day 28
Change in distance covered for 6 minutes (6MWD) at Weeks 2 and 4 from the baseline value (based on 6-minute walk test)
Time frame: Day 1- Day 28
Change in the score of the Borg scale at Weeks 2 and 4 from the baseline value (based on the 6-minute walk test)
Time frame: Day 1- Day 28
Change in forced expiratory volume for the first second (FEV1) according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values
Time frame: Day 1- Day 28
Change in FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values
Time frame: Day 1- Day 28
Change in FEV1/FVC according to spirometry data at Weeks 1, 2, 3 and 4 relative to the baseline values
Time frame: Day 1- Day 28
Change in DLCO according to bodyplethysmography at Week 2 and Week 4 relative to baseline values
Time frame: Day 1- Day 28
Change in Total Lung Capacity (TLC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values
Time frame: Day 1- Day 28
Change in Functional Residual Capacity (FRC) according to bodyplethysmography at Week 2 and Week 4 relative to baseline values
Time frame: Day 1- Day 28
The rate of reduction in the lung damage degree based on the computed tomography (CT) at Week 4 relative to the baseline value
Classification of lung damage includes the following stages: CT-0 (norm), CT-1 (\< 25% of lung damage), CT-2 (25-50% of lung damage), CT-3 (50-75% of lung damage), CT-4 (\> 75% of lung damage)
Time frame: Day 1- Day 28
Change in mMRC Dyspnea Score in Week 1, Week 2, Week 3, and Week 4 from the baseline value
Time frame: Day 1- Day 28
Change in the overall score of the KBILD Questionnaire at Week 2 and Week 4 relative to the baseline value
Time frame: Day 1- Day 28
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