The siCoV/KK46 Drug Open-safety Study

Study Overview
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Brief Summary
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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
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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.

Official Title
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An Open-safety Study of the siCoV/KK46 Drug Administered Via an Inhaled Route in Healthy Volunteers

Conditions
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COVID-19

Intervention / Treatment
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* Drug: siCoV/KK46


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men aged 18 to 45 years Able to give informed consent and attend all study visits Blood pressure level: systolic blood pressure 100 to 139 mm Hg, diastolic blood pressure 60 to 89 mm Hg. Heart rate from 60 to 90 beats per minute Body mass index 18.5 -30. The body weight should be ≥ 55 kg; Men must agree to use the reliable contraception while on study medication and for posttrial contraception for 30 days Be able to understand and comply with protocol requirements Exclusion Criteria: A burdened allergic history. Previous adverse reactions to the active substance and/or excipients included in the drug. Chronic diseases of the cardiovascular, lymphatic, respiratory, nervous, endocrine, digestive, musculoskeletal, integumentary, immune systems, as well as the genitourinary apparatus and hematopoietic organs. Weakness of the inspiratory muscles of respiration (according to spirometry result). Acute infectious diseases symptoms in the last 4 weeks before screening. 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. Regular treatment with any medicine less than 2 weeks prior to screening and single treatment less than 7 days prior screening. Donation of blood or plasma less than 3 months prior to screening. Transfusion of blood and/or its components less than 3 months prior to screening. Participation in other investigational drug or device clinical trials within 90 days prior to screening. 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. Smoking more than 10 cigarettes currently, or history of smoking this number of cigarettes within 6 months prior to screening. Positive blood tests for HIV, hepatitis B and С, syphilis. Positive PCR test results for SARS-CoV-2(nasal swab). Positive result on a urine drug screening test. Positive test for ethanol vapor in exhaled air. Planned hospitalization during the period of participation in the study, for any reason other than hospitalization specified by this protocol. Inability or inability to follow the protocol, to perform the procedures prescribed by the protocol, to follow a diet, activity regime. 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: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Interventional 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: siCoV/KK46<br>Drug contains anti-SARS-CoV-2 siRNAs/KK-46 (peptide dendrimer) complexes for inhalation use | Drug: siCoV/KK46<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| This is an open-label, dose-escalation phase I study to assess the safety and tolerability of siCoV/KK46 in healthy volunteers | Adverse Events | Within 72 hours after single treatment with siCoV/KK46 | 
| Vital Signs | Blood pressure in mm Hg | Within 72 hours after single treatment with siCoV/KK46 | 
| Body Temperature control | Taking an Axillary Temperature | Within 72 hours after single treatment with siCoV/KK46 | 
| Heart rate | Heart Rate in beats per minute | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Potassium level | Measurement of Potassium level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Sodium level | Measurement of Sodium level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Chloride level | Measurement of Chloride level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Bicarbonate level | Measurement of Bicarbonate level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Calcium level | Measurement of Calcium level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Phosphate level | Measurement of Phosphate level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Creatine phosphokinase level | Measurement of Creatine phosphokinase level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Blood urea nitrogen level | Measurement of Blood urea nitrogen level | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Albumin level | Measurement of Albumin level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Protein level | Measurement of Protein level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Aspartate transaminase level | Measurement of Aspartate transaminase level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Alanine transaminase level | Measurement of Alanine transaminase level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Alkaline phosphatase level | Measurement of Alkaline phosphatase level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Clinical Chemistry to asses Bilirubin level | Measurement of Bilirubin level in blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Blood Glucose Test | Measurement of Glucose level | Within 72 hours after single treatment with siCoV/KK46 | 
| Haematology blood test | Qualitative and quantitative composition of the cellular components of the blood | Within 72 hours after single treatment with siCoV/KK46 | 
| Urinalysis | Physical, chemical, and microscopic examination of urine | Within 72 hours after single treatment with siCoV/KK46 | 
| 12-Lead Electrocardiogram | Measurement of Heart rate; PR, QRS, RR, QT and QTc intervals from digital recordings | Within 72 hours after single treatment with siCoV/KK46 | 

 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