Сlinical Trial of Efficacy and Safety of Prospekta in the Treatment of Post-COVID-19 Asthenia.

Study Overview
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Brief Summary
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The multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial. The objective of this study is to evaluate the efficacy and safety of Prospekta in the treatment of asthenia in patients after the coronavirus infectious disease (COVID-19).

Detailed Description
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Design: the multicenter, double-blind, placebo-controlled, parallel-group, randomized clinical trial. The study will enroll adult patients of either gender aged 18 to 65 years after new coronavirus infection of 2019 (COVID-19) with symptoms of asthenia that appeared during or after an acute coronavirus infection (COVID-19) and persisting 4 to 12 weeks from the onset of coronavirus infection. After the patient signs the patient information sheet and the informed consent form for participation in the study, complaints, medical history, physical examination, registration of vital signs are collected, the patient fills in the Fatigue Severity Scale (FSS) and Hospital Anxiety and Depression Scale (HADS). A six-minute walk test (6MWT) is carried out. The physician evaluates the severity of asthenia with FSS scale and records concomitant medications, co-morbidities and concurrent conditions. If a patient meets all inclusion criteria and does not have any of the exclusion criteria at Visit 1 (Day 1), he/she is randomized to one of two groups: Group 1 - patients receive Prospekta at a dose of 1 tablet twice daily for 4 weeks; Group 2 - patients receive placebo on the study drug regimen. The trial will use electronic patient diaries (EPD). The patient should record any possible deterioration (if applicable) in the EPD. At Visit 1 (Day 1), the physician will provide guidance on how to work with EPD, so that the patient can use it independently in the future. At Visit 2 (Week 4 ± 3 days), the physician will collect patient's complaints, record physical examination data and vital signs as well as any changes in concurrent diseases and conditions. The patient fills out the FSS and HADS scales. A 6MWT is carried out. The physician monitors the prescribed treatment and use of concomitant medications, evaluates the safety of the study treatment and patient's compliance, filling out the diary. The patient stops taking the study drug. At the end of the study treatment period, the patient is monitored for 4 weeks (follow-up period). At Visit 3 (final visit, Week 8 ± 3 days), the physician collects patient's complaints, records physical examination data and vital signs, changes in concomitant diseases and conditions. The patient fills in the FSS and HADS scales. A 6MWT is carried out. The physician evaluates the safety of the study treatment, checks the completion of the diary. During the study the patients are allowed to take medications for their chronic conditions, except for medicines listed as Prohibited concomitant treatment.

Official Title
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A Multicenter, Double-blind, Placebo-controlled, Parallel-group, Randomized Clinical Trial of Efficacy and Safety of Prospekta in the Treatment of Patients With Post-COVID-19 Asthenia.

Conditions
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Post-acute COVID-19 Syndrome

Intervention / Treatment
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* Drug: Prospekta
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults of either gender aged 18 to 65 years inclusive. Patients within 4-12 weeks of the confirmed COVID-19 onset . Symptoms of asthenia that appeared during or after an acute new coronavirus infection (COVID-19), persisting from 4 to 12 weeks from the onset of coronavirus infection. Presence of asthenia (≥36 on the FSS scale). Patients who agreed to use a reliable method of contraception during the study (for men and women with reproductive potential). Presence of a signed information sheet and informed consent form for participation in a clinical trial. Exclusion Criteria: History / suspicion of cancer of any localization (with the exception of benign neoplasms). More than 75% of lung tissue damage during the period of COVID-19 disease (CT 4). Cerebrovascular diseases with the development of moderate to severe cognitive impairments. Uncontrolled arterial hypertension characterized by the following blood tension values: systolic blood pressure > 180 mm Hg and/or diastolic blood pressure > 110 mm Hg. Myocardial infarction, stroke in the previous 6 months. Nervous system disorders with persistent neurological impairment. Autoimmune diseases. Decompensated diseases of the cardiovascular system, liver, kidney, gastrointestinal tract, and metabolic, respiratory, endocrine or hematological diseases, peripheral vascular disorders. Any severe comorbidity which, in the opinion of the investigator, may affect patient participation in the clinical trial. Hypersensitivity to any of the components of the study drug. Hereditary lactose intolerance, lactose malabsorption, including congenital or acquired lactase or other disaccharidase deficiency, galactosemia. Pregnancy, breast-feeding; childbirth less than 3 months prior to the inclusion in the trial, unwillingness to use contraceptive methods during the trial (for men and women with reproductive potential). Patients, who, from the investigator's point of view, will not comply with study observation requirements or study drug administration procedures.. Prior history of mental illness, alcoholism or drug abuse, that the investigator's opinion, will interfere with successful study procedures. Use of any medications listed in Prohibited concomitant treatment within 1 week before enrollment. Participation in other clinical studies within 3 months prior to enrollment in the study. Patients who are related to any of the on-site research personnel directly involved in the conduct of the trial or are an immediate relative of the study investigator. Immediate relative means husband, wife, parent, son, daughter, brother, or sister (regardless of whether they are natural or adopted). Participants who work for OOO NPF MATERIA MEDICA HOLDING (i.e. the company's employees, temporary contract workers, designated officials responsible for carrying out the research or any immediate relatives of the aforementioned).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double-blind, placebo-controlled, parallel-group, randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prospekta<br>Tablet for oral use. 1 tablet twice daily. The tablets are taken outside of meals (between meals or 15 minutes before eating or drinking), keep the tablets in the mouth, without swallowing, until completely dissolved. | Drug: Prospekta<br>* Oral administration.<br>|
| Placebo Comparator: Placebo<br>Tablet for oral use. Placebo using Prospekta scheme. | Drug: Placebo<br>* Oral administration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in the mean FSS score. | Fatigue Severity Scale (FSS). Change in the mean FSS score after 4 weeks of treatment. Based on medical records.1 indicates strongly disagree and 7 indicates strongly agree. | after 4 weeks of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in distance of the 6-minute walk test. | Change in distance when performing the 6-minute walk test after 4 weeks of treatment. The test is carried out with the aim of objectively assessing the patient's physical tolerance. The patient should walk the maximum possible distance for himself at his own pace on a flat surface in 6 minutes. | after 4 weeks of treatment | 
| Change in the severity of anxiety and depression on the HADS subscales. | Hospital Anxiety and Depression Scale (HADS). Change in the severity of anxiety and depression on the HADS subscales after 4 weeks of treatment. The scale is composed of 14 statements serving 2 subscales: anxiety (odd items - 1, 3, 5, 7, 9, 11, 13) and depression (even items - 2, 4, 6, 8, 10, 12 , 14). Each statement corresponds to 4 answer options, reflecting the gradation of the severity of the sign and coded according to the increase in the severity of the symptom from 0 (no) to 3 (maximum severity). When interpreting the results, the total indicator for each subscale is taken into account, while there are 3 areas of its values: 0-7 - norm (absence of reliably expressed symptoms of anxiety and depression); 8-10 - subclinical anxiety / depression; 11 and above - clinical anxiety / depression. | after 4 weeks of treatment | 
| Change in the mean FSS score within follow-up period. | Change in mean FSS score over 4 weeks of follow-up period at the end of treatment. | within 4 weeks of follow-up | 
| Change in distance of the 6-minute walk test within follow-up period. | Change in distance when performing the 6-minute walk test over a 4-week follow-up period at the end of treatment. | within 4 weeks of follow-up | 
| Change in the severity of anxiety and depression on the HADS subscales within follow-up period. | Change in the severity of anxiety and depression on the HADS subscales over a 4-week follow-up period at the end of treatment. | within 4 weeks of follow-up | 
| Changes in vital signs (pulse rate (heart rate)). | Based on medical records. Vital signs will be measured in a medical setting. | after 4 weeks of treatment and within 4 weeks of the follow-up period at the end of the treatment. | 
| Changes in vital signs (respiration rate (breathing rate)). | Based on medical records. Vital signs will be measured in a medical setting. | after 4 weeks of treatment and within 4 weeks of the follow-up period at the end of the treatment. | 
| Changes in vital signs (blood pressure). | Based on medical records. Vital signs will be measured in a medical setting. | after 4 weeks of treatment and within 4 weeks of the follow-up period at the end of the treatment. | 
| The presence and nature of of adverse events (AEs). | The presence and nature of adverse events, their intensity (severity), causal relationship to the study drug, outcome. Based on medical records. | 4 weeks of treatment and within 4 weeks of follow-up |