SARS-CoV-2 (COVID-19) Infection
Conditions
Keywords
SARS-CoV-2, First in Human, Safety, Tolerability, Systemic Exposure
Brief summary
The goal of this First in Human Phase 1 clinical trial is to to assess the safety, tolerability, and systemic exposure of single, twice daily (BID) doses and repeated BID doses of ascending dosing by intranasal administration of Apo-Si-K170AC76 in healthy adult subjects. The primary objective is to evaluate the safety and tolerability of single, BID, and repeated BID, ascending dosing of Apo-Si-K170A-C76 administered intranasally (IN) in healthy adult subjects. The secondary objective is to evaluate the systemic exposure to Apo-Si-K170A-C76 following intranasal administration in healthy adult subjects under the aforementioned administration regimens. Researchers will compare the active drug Apo-Si-K170A-C76 to placebo control.
Detailed description
Upon signing the informed consent, the subjects underwent a screening period for eligibility evaluation. Subjects were admitted to the Research Unit on Day 1 and eligibility was confirmed again. Eligible subjects, as determined by the Principal Investigator (PI), were randomized as close as possible prior to1st drug administration on Day 1, to receive either intranasal Apo-Si-K170A-C76 or matching placebo. Dosing depended on the cohort the subjects were assigned to. Intranasal (IN) administration was performed to both nostrils of all participants. The nasal spray device contains the Study Drug at 20 mg/mL and delivers 0.1 mL volume per actuation. The subjects received 1-3 actuations per nostril alternately, according to dosing group. Thus, during each administration cohort, dosages registered as dose/nostril are received twice per subject, one dose to each nostril. The study was composed of 7 dosing cohorts. Administration in cohorts 1-5 took place on Day 1. Administration to cohorts 6-7 took place from Day 1 to Day 5. The study drug (or placebo) was administered to both nostrils via intranasal spray, while the subject is seated. All subjects arrived at the clinic for a follow up visit 7±2 days after last day of administration. Cohort 1 involved an initial administration of a single (low) dose of Apo-Si-K170A-C76 (2mg/100μl/nostril, to both nostrils). Cohort 2 involved administration of a single dose of Apo- Si-K170A-C76 at a double dose of the first dose (4mg/200μl/nostril, to both nostrils). Cohort 3 involved administration of a single dose of Apo-Si-K170AC76 at the target dose (x3 of first dose, 6mg/300μl/nostril, to both nostrils). Cohort 4 involved BID administration of the same dose as cohort 2, and cohort 5 involved BID administration of the same dose as cohort 3. All BID dosing was separated by 6 hours. Cohort 6 involved administration of repeated BID doses of Apo-Si-K170A (at the same dose level or lower than that administered in Cohort 4) taken from Day 1 to Day 5. Cohort 7, which aims to reach target dose, involved administration of repeated BID doses of Apo-Si-K170A-C76 (at the same dose level or lower than that administered in Cohort 5) taken also from Day 1 to Day 5.
Interventions
DRUGApo-Si-K170A-C76
Apo-Si-K170A-C76 is an small interfering RNA (siRNA) against SARS-CoV-2
DRUGPlacebo
5% glucose, 0.5% benzyl alcohol in RNase free water
Sponsors
Interna Therapeutics Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
The study is composed of 7 dosing cohorts. Cohorts #1-3 for single ascending doses; Cohorts #4-5 for BID ascending doses; Cohorts #6-7 for repeated BID dosing for 5 consecutive days, of ascending doses.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Male and female participants must be ≥ 18 years old. * Understands the study procedures described in the Informed Consent Form (ICF), be willing and able to comply with the protocol, and provides written consent. * Not pregnant or lactating and willing to comply with the contraceptive requirements from enrolment to 3 months post last dose. Contraceptive requirements include the following: * Use a condom with a spermicide to prevent pregnancy in a female partner or to prevent exposure of any partner (male and female) to the study intervention treatment. * Male sterilization with the appropriate post vasectomy documentation of the absence of sperm in the ejaculate (please note that the use of condom with spermicide will still be required to prevent partner exposure). This applies only to males participating in the study. * In addition, for female partners and female participants of childbearing potential, must use another form of contraceptive such as one of the highly effective methods (pills, Intra Uterine Device (IUD)). * True abstinence - sexual abstinence is considered as a highly effective method only if defined as refraining from heterosexual intercourse during the entire period of risk associated with the study treatments. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the subject. * In addition to the contraceptive requirements above, male subjects must agree not to donate sperm for 3 months post last dose of treatment. * Subject is in good health with no history of clinically significant medical conditions (as described in
Exclusion criteria
) that would interfere with subject safety, as defined by relevant medical history, physical examination and routine laboratory tests, and ECG, and as determined by the investigator at an admission evaluation. * Subjects will have documented relevant medical history prior to entering the study and/or following relevant medical history review with the study physician at screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with abnormal vital signs | 5 days | Vital signs were measured in a semi-supine position after five minutes of rest and included temperature, systolic blood pressure (SBP), diastolic blood pressure (DBP) , heart rate, respiratory rate. Number of participants with abnormality in any vital signs from baseline to EOS are presented. |
| The safety and tolerability, as evaluated by Adverse Events (AEs) classification, following single, twice-daily (BID) and repeated BID ascending doses of Apo-Si-K170A-C76 following IN in healthy participants. | 5 days | Adverse events (AE) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA, most updated version) terminology and presented in tables by System Organ Class (SOC). AE data will be listed individually and summarized by SOC and by Preferred Term (PT) within a system organ class. |
| The safety and tolerability, as evaluated by Treatment-Emergent Adverse Events (TEAEs) frequency, following single, twice-daily (BID) and repeated BID ascending doses of Apo-Si-K170A-C76 following IN in healthy participants. | 5 days | Frequency of TEAEs and drug-related adverse events will be summarized in tables by SOC, PT and by seriousness. |
| The safety and tolerability, as evaluated by AEs classification, blood tests and other physiological parameters, following single, twice-daily (BID) and repeated BID ascending doses of Apo-Si-K170A-C76 following IN in healthy participants. | 5 days | Adverse events (AE) will be coded using the Medical Dictionary for Regulatory Activities (MedDRA, most updated version) terminology and presented in tables by System Organ Class (SOC). AE data will be listed individually and summarized by SOC and by Preferred Term (PT) within a system organ class. Frequency of Treatment-Emergent Adverse Events (TEAEs) and drug-related adverse events will be summarized in tables by SOC, PT and by seriousness. Concomitant medications entered into the database will be coded using the public World Health Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic Chemical classification system. Change from Baseline to end of study (EOS) in safety laboratory, vital signs and physical examination will be summarized in appropriate tables. |
| The safety and tolerability, as evaluated by medicinal use during study, following single, twice-daily (BID) and repeated BID ascending doses of Apo-Si-K170A-C76 following IN in healthy participants. | 5 days | Concomitant medications entered into the database will be coded using the public World Health Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic Chemical classification system. |
| Number of participants with abnormal laboratory tests | 5 days | Blood and urine samples were collected for the assessment of laboratory tests. Number of participants with abnormal laboratory test parameters (i.e. outside normal parameter tests results from baseline to EOS) are presented. |
| Number of participants with physical examination | 5 days | Physical examination was performed extensively and focally throughout the study duration, from baseline to EOS. Number of participants with abnormal physical examination are presented. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Systemic exposure be determined by measuring serum concentrations (ng/ml) of Apo-Si-K170A-C76 obtained in each cohort, at specific time points. | 5 days | Bioanalytical analysis of the concentration of the active drug in serum samples |
Countries
Israel
Outcome results
None listed