Evaluation of Safety & Efficacy of MIR 19 ® Inhalation Solution in Patients With Moderate COVID-19

Study Overview
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Brief Summary
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This is Phase 2 multi-center controlled randomized study to assess the efficacy and safety of MIR 19® via 14 days of treatment of participants with symptomatic moderate COVID-19. The purpose of this study is to evaluate the efficacy, safety and daily dose of MIR 19 ® for the treatment of the hospitalized patients with infection caused by SARS-CoV-2 (COVID-19) who did not require treatment in the intensive care unit. Based on preclinical data studying antiviral effect of MIR 19® in vitro and in vivo (Khaitov M.R. et all 2021), the investigators hypothesized that SARS-CoV-2 inhibition with MIR 19® could potentially reduce pulmonary inflammation, thereby improving COVID-19 patient outcomes.

Detailed Description
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This is Phase 2 multi-center controlled randomized study to assess the efficacy and safety of MIR 19 ® in male and female volunteers with symptomatic moderate COVID-19 who did not require treatment in the intensive care unit. The MIR 19® is a complex of siRNA, targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and peptide dendrimer KK-46. This study involved 3 cohorts who received: standard therapy which included symptomatic treatment as well as etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. 3.7 mg of the MIR 19 ® via inhalation route plus standard therapy which included symptomatic treatment, without any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. 11.1 mg of the MIR 19 ® via inhalation route plus standard therapy which included symptomatic treatment, without any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. All subjects will undergo scheduled safety and efficacy assessments while in the clinical unit and as outpatients to the end of the follow-up period.

Official Title
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Open Multicenter Controlled Clinical Trial to Evaluate Safety and Efficacy of Aerosolized MIR 19 ® Inhalation in Patients With Moderate COVID-19 Who Did Not Require Treatment in the Intensive Care Unit.

Conditions
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COVID-19

Intervention / Treatment
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* Drug: MIR 19 ®
* Combination Product: Standard COVID-19 therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or non-pregnant female aged 18 to 65 years hospitalized with moderate COVID-19 infection: body temperature > 37.5 °C; respiratory rate > 22/min; shortness of breath during physical exertion; typical coronavirus-associated chest computed tomography (CT) changes (CT1- CT2); pulse oximetry levels SpO2< 95%. Able to give informed consent and attend all study visits Positive PCR-test for COVID-19 ≤72 hours prior to randomization The patient's ability to inhale the experimental drug Participants must agree to use the reliable contraception while on study medication and for posttrial contraception for 3 month Key Exclusion Criteria: Fever > 38.5°C. Cough severity is less than 1 point on a 4-point scale. Respiratory rate > is more than 30 / min SpO2 ≤ 93%. Decreased level of consciousness, agitation. Unstable hemodynamics (systolic blood pressure less than 100 mmHg or diastolic blood pressure less than 60 mmHg). The need to require mechanical ventilation beyond the screening/ randomization. Long-term systemic corticosteroid exposure. Autoimmune or inflammatory diseases (systemic / localized). Positive blood tests for HIV, hepatitis B and С, syphilis. Pregnancy and breast-feeding Previous adverse reactions to the active substance and/or excipients included in the drug. Any use of anti-viral medications or immunomodulatory agents up to 7 days before participating in the study Chronic diseases of the cardiovascular system Type 1 diabetes The following laboratory parameters are excluded: Alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, total and direct bilirubin >4 x upper limit of normal (ULN); Treatment with any medicine that have a pronounced effects on the blood coagulation system (expect for COVID-19 treatment), including combined oral contraceptives. Treatment with any medicine that can affect cardiac conduction Participation in other investigational drug or device clinical trials within 90 days prior to screening. History of alcohol, drug or chemical abuse. Mental illness. Receipt of plasma from a person who recovered from COVID-19 (convalescent plasma) up to 14 days before participating in the study, vaccination against SARS-CoV-2 , the need for extracorporeal membrane oxygenation. Any conditions that, according to the researcher's, may be a contraindication to the participation in the study.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MIR 19 ®<br>Study participants from experimental groups, in addition to standard COVID-19 therapy, received the MIR 19 ® (2 inhalations per day with a single dose of 1.85 or 5.55 mg at intervals of 7-8 hours for 14 days).The standard therapy in this group included symptomatic treatment without use of any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b | Drug: MIR 19 ®<br>* Drug contains anti-SARS-CoV-2 siRNAs/KK-46 (peptide dendrimer) complexes for inhalation use.<br>Combination Product: Standard COVID-19 therapy<br>* Therapy carried out in accordance with the current version of the temporary methodological recommendations of the Ministry of Health of the Russian Federation for the treatment of COVID-19 infection. This therapy included symptomatic treatment as well as etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. In the experimental groups treated with MIR 19 ®, the therapy included symptomatic treatment without use of any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b<br>|
| Active Comparator: Standard COVID-19 therapy<br>In the comparison group, therapy was carried out in accordance with the current version of the temporary methodological recommendations of the Ministry of Health of the Russian Federation for the treatment of COVID-19 infection.The standard therapy included symptomatic treatment as well as etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. In the experimental groups treated with MIR 19 ®, the therapy included symptomatic treatment without use of any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. | Combination Product: Standard COVID-19 therapy<br>* Therapy carried out in accordance with the current version of the temporary methodological recommendations of the Ministry of Health of the Russian Federation for the treatment of COVID-19 infection. This therapy included symptomatic treatment as well as etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b. In the experimental groups treated with MIR 19 ®, the therapy included symptomatic treatment without use of any etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relief of fever | Reduction in axillary temperature below 37 °C without antipyretic drugs use | Within 14 days | 
| Respiratory rate | Respiratory rate ≤ 22 per minute | Within 14 days | 
| Oxygen saturation | SpO2 > 94% | Within 14 days | 
| Severity of cough | Severity in a patient's cough no more than 1 point on a four-point scale | Within 14 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, siRNA, SARS-CoV-2