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

NCT ID: NCT05184127

Last Updated: 2022-01-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 156 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-27
• Study Completion Date: 2021-09-07

Brief Summary

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

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.

Conditions

COVID-19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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

Group Type: EXPERIMENTAL

MIR 19 ®

Intervention Type: DRUG

Drug contains anti-SARS-CoV-2 siRNAs/KK-46 (peptide dendrimer) complexes for inhalation use.

Standard COVID-19 therapy

Intervention Type: COMBINATION_PRODUCT

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

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.

Group Type: ACTIVE_COMPARATOR

Standard COVID-19 therapy

Intervention Type: COMBINATION_PRODUCT

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

Interventions

MIR 19 ®

Drug contains anti-SARS-CoV-2 siRNAs/KK-46 (peptide dendrimer) complexes for inhalation use.

Intervention Type: DRUG

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

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

St. Petersburg Research Institute of Vaccines and Sera

OTHER_GOV

Sponsor Role: collaborator

National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

NRC Institute of Immunology FMBA

Moscow, , Russia

Countries

Russia

References

Khaitov M, Nikonova A, Kofiadi I, Shilovskiy I, Smirnov V, Elisytina O, Maerle A, Shatilov A, Shatilova A, Andreev S, Sergeev I, Trofimov D, Latysheva T, Ilyna N, Martynov A, Rabdano S, Ruzanova E, Savelev N, Pletiukhina I, Safi A, Ratnikov V, Gorelov V, Kaschenko V, Kucherenko N, Umarova I, Moskaleva S, Fabrichnikov S, Zuev O, Pavlov N, Kruchko D, Berzin I, Goryachev D, Merkulov V, Shipulin G, Udin S, Trukhin V, Valenta R, Skvortsova V. Treatment of COVID-19 patients with a SARS-CoV-2-specific siRNA-peptide dendrimer formulation. Allergy. 2023 Jun;78(6):1639-1653. doi: 10.1111/all.15663. Epub 2023 Feb 14.

Reference Type: DERIVED

PMID: 36721963 (View on PubMed)

Other Identifiers

SiCoV/KK46- 2021_CSR

Identifier Type: -

Identifier Source: org_study_id