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

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.

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.

Study Overview

• Status: Completed
• Conditions: COVID-19
• Intervention / Treatment: Drug: MIR 19 ®; Combination product: Standard COVID-19 therapy

Detailed Description

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:

1. standard therapy which included symptomatic treatment as well as etiotropic drugs such as Favipiravir, Umifenovir, Remdesivir, convalescent plasma and interferon α-2b.
2. 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.
3. 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.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Phase 2

Contacts and Locations

Study Locations

• Russian Federation
  • Moscow, Russian Federation, 115478
    • NRC Institute of Immunology FMBA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. 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%.
2. Able to give informed consent and attend all study visits
3. Positive PCR-test for COVID-19 ≤72 hours prior to randomization
4. The patient's ability to inhale the experimental drug
5. Participants must agree to use the reliable contraception while on study medication and for posttrial contraception for 3 month

Key Exclusion Criteria:

1. Fever > 38.5°C.
2. Cough severity is less than 1 point on a 4-point scale.
3. Respiratory rate > is more than 30 / min
4. SpO2 ≤ 93%.
5. Decreased level of consciousness, agitation.
6. Unstable hemodynamics (systolic blood pressure less than 100 mmHg or diastolic blood pressure less than 60 mmHg).
7. The need to require mechanical ventilation beyond the screening/ randomization.
8. Long-term systemic corticosteroid exposure.
9. Autoimmune or inflammatory diseases (systemic / localized).
10. Positive blood tests for HIV, hepatitis B and С, syphilis.
11. Pregnancy and breast-feeding
12. Previous adverse reactions to the active substance and/or excipients included in the drug.
13. Any use of anti-viral medications or immunomodulatory agents up to 7 days before participating in the study
14. Chronic diseases of the cardiovascular system
15. Type 1 diabetes

16. 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);

17. Treatment with any medicine that have a pronounced effects on the blood coagulation system (expect for COVID-19 treatment), including combined oral contraceptives.
18. Treatment with any medicine that can affect cardiac conduction
19. Participation in other investigational drug or device clinical trials within 90 days prior to screening.
20. History of alcohol, drug or chemical abuse.
21. Mental illness.
22. 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.
23. Any conditions that, according to the researcher's, may be a contraindication to the participation in the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MIR 19 ®; 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 ®; Drug contains anti-SARS-CoV-2 siRNAs/KK-46 (peptide dendrimer) complexes for inhalation use.; Combination product: Standard COVID-19 therapy; 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
Active Comparator: Standard COVID-19 therapy; 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; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
• Collaborators: St. Petersburg Research Institute of Vaccines and Sera

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): September 7, 2021
• Study Completion (Actual): September 7, 2021

Study Registration Dates

• First Submitted: January 7, 2022
• First Submitted That Met QC Criteria: January 7, 2022
• First Posted (Actual): January 11, 2022

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: SARS-CoV-2; COVID-19; siRNA
• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: SiCoV/KK46- 2021_CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No