COVID-19
Conditions
Keywords
COVID-19, siRNA, SARS-CoV-2
Brief summary
This is an open-label, dose-escalation phase I study to assess the safety and tolerability of siCoV/KK46 in healthy volunteers. The purpose of this study is to determine the maximum daily dose of siCoV/KK46 as a single agent in adult healthy participants. Based on preclinical data from this institution, the investigators hypothesize that SARS-CoV-2 inhibition with siCoV/KK46 could potentially reduce pulmonary inflammation, thereby improving COVID-19 patient outcomes.
Detailed description
This is an open-label, dose-escalation phase I study to assess the safety and tolerability of single and multiple doses of siCoV/KK46 in healthy male volunteers. This study include 3 cohorts received 3.7 mg, 11.1 mg, 22.2 mg of the siCoV/KK46, respectively, via inhalation route. All subjects will undergo scheduled safety and tolerability assessments while in the clinical unit and as outpatients to the end of the follow-up period.
Interventions
DRUGsiCoV/KK46
The modified phase I 3 + 1+1 study design was used in dose escalation from low dose to high dose to determine the maximum daily dose. Sequential assignment of Patient cohorts to one of three dose levels of inhaled siCoV/KK46: 3.7 mg, 11.1 mg, 22.2 mg.
Sponsors
St. Petersburg Research Institute of Vaccines and Sera
National Research Center - Institute of Immunology Federal Medical-Biological Agency of Russia
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This is a dose-escalation trial, all participants will receive single or multiple treatment with siCoV/KK46 via an inhaled route. Participants enrolled in this trial may receive one of the following doses: Cohort 1: 3.7 mg; Cohort 2: 11.1 mg; Cohort 3: 22.2 mg
Eligibility
Sex/Gender
MALE
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
1. Healthy men aged 18 to 45 years 2. Able to give informed consent and attend all study visits 3. Blood pressure level: systolic blood pressure 100 to 139 mm Hg, diastolic blood pressure 60 to 89 mm Hg. 4. Heart rate from 60 to 90 beats per minute 5. Body mass index 18.5 -30. The body weight should be ≥ 55 kg; 6. Men must agree to use the reliable contraception while on study medication and for posttrial contraception for 30 days 7. Be able to understand and comply with protocol requirements
Exclusion criteria
1. A burdened allergic history. 2. Previous adverse reactions to the active substance and/or excipients included in the drug. 3. Chronic diseases of the cardiovascular, lymphatic, respiratory, nervous, endocrine, digestive, musculoskeletal, integumentary, immune systems, as well as the genitourinary apparatus and hematopoietic organs. 4. Weakness of the inspiratory muscles of respiration (according to spirometry result). 5. Acute infectious diseases symptoms in the last 4 weeks before screening. 6. Treatment with any medicine that have a pronounced effect on hemodynamics and affects the liver function (barbiturates, omeprazole, cimetidine, etc.) within 2 months prior to screening. 7. Regular treatment with any medicine less than 2 weeks prior to screening and single treatment less than 7 days prior screening. 8. Donation of blood or plasma less than 3 months prior to screening. 9. Transfusion of blood and/or its components less than 3 months prior to screening. 10. Participation in other investigational drug or device clinical trials within 90 days prior to screening. 11. Drinking of more than 10 units of alcohol (1 unit of alcohol is equivalent to 330 mL of beer, 150 mL of wine or 40 mL of strong alcoholic drinks) per week within the last month prior to inclusion in the study and/or history of alcohol, drug or chemical abuse. 12. Smoking more than 10 cigarettes currently, or history of smoking this number of cigarettes within 6 months prior to screening. 13. Positive blood tests for HIV, hepatitis B and С, syphilis. Positive PCR test results for SARS-CoV-2(nasal swab). 14. Positive result on a urine drug screening test. 15. Positive test for ethanol vapor in exhaled air. 16. Planned hospitalization during the period of participation in the study, for any reason other than hospitalization specified by this protocol. 17. Inability or inability to follow the protocol, to perform the procedures prescribed by the protocol, to follow a diet, activity regime. 18. Any conditions that, according to the researcher's, may be a contraindication to the participation in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| This is an open-label, dose-escalation phase I study to assess the safety and tolerability of siCoV/KK46 in healthy volunteers | Within 72 hours after single treatment with siCoV/KK46 | Adverse Events |
| Vital Signs | Within 72 hours after single treatment with siCoV/KK46 | Blood pressure in mm Hg |
| Body Temperature control | Within 72 hours after single treatment with siCoV/KK46 | Taking an Axillary Temperature |
| Heart rate | Within 72 hours after single treatment with siCoV/KK46 | Heart Rate in beats per minute |
| Clinical Chemistry to asses Potassium level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Potassium level in blood |
| Clinical Chemistry to asses Sodium level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Sodium level in blood |
| Clinical Chemistry to asses Chloride level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Chloride level in blood |
| Clinical Chemistry to asses Bicarbonate level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Bicarbonate level in blood |
| Clinical Chemistry to asses Calcium level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Calcium level in blood |
| Clinical Chemistry to asses Phosphate level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Phosphate level in blood |
| Clinical Chemistry to asses Creatine phosphokinase level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Creatine phosphokinase level in blood |
| Clinical Chemistry to asses Blood urea nitrogen level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Blood urea nitrogen level |
| Clinical Chemistry to asses Albumin level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Albumin level in blood |
| Clinical Chemistry to asses Protein level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Protein level in blood |
| Clinical Chemistry to asses Aspartate transaminase level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Aspartate transaminase level in blood |
| Clinical Chemistry to asses Alanine transaminase level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Alanine transaminase level in blood |
| Clinical Chemistry to asses Alkaline phosphatase level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Alkaline phosphatase level in blood |
| Clinical Chemistry to asses Bilirubin level | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Bilirubin level in blood |
| Blood Glucose Test | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Glucose level |
| Haematology blood test | Within 72 hours after single treatment with siCoV/KK46 | Qualitative and quantitative composition of the cellular components of the blood |
| Urinalysis | Within 72 hours after single treatment with siCoV/KK46 | Physical, chemical, and microscopic examination of urine |
| 12-Lead Electrocardiogram | Within 72 hours after single treatment with siCoV/KK46 | Measurement of Heart rate; PR, QRS, RR, QT and QTc intervals from digital recordings |
Countries
Russia
Outcome results
None listed