Safety, Tolerability, and Systemic Exposure of Apo-Si- K170A-C76 in Healthy Volunteers

NCT07095049 | Active Not Recruiting Phase 1 DMC

• 1 other identifier: Sir-001
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

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.

Conditions

SARS-CoV-2 (COVID-19) Infection

Keywords

SARS-CoV-2; First in Human; Safety; Tolerability; Systemic Exposure

Outcome Measures

Primary Outcomes (7)

• 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.

  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.

  5 days

• 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.

  Frequency of TEAEs and drug-related adverse events will be summarized in tables by SOC, PT and by seriousness.

  5 days

• 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.

  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.

  5 days

• 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.

  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.

  5 days

• Number of participants with abnormal laboratory tests

  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.

  5 days

• Number of participants with physical examination

  Physical examination was performed extensively and focally throughout the study duration, from baseline to EOS. Number of participants with abnormal physical examination are presented.

  5 days

• Number of participants with abnormal vital signs

  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.

  5 days

Secondary Outcomes (1)

• 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

Study Arms (2)

Intranasal Apo-Si-K170A-C76 Solution of 20 mg/ml in 5% glucose, 0.5% Benzyl Alcohol (BA) in water

EXPERIMENTAL

Intervention drug intranasal administration

Drug: Apo-Si-K170A-C76

5% glucose, 0.5% benzyl alcohol in RNase free water

PLACEBO COMPARATOR

Intranasal

Drug: Placebo

Interventions

Apo-Si-K170A-C76 DRUG

Apo-Si-K170A-C76 is an small interfering RNA (siRNA) against SARS-CoV-2

Also known as: c76

Intranasal Apo-Si-K170A-C76 Solution of 20 mg/ml in 5% glucose, 0.5% Benzyl Alcohol (BA) in water

Placebo DRUG

5% glucose, 0.5% benzyl alcohol in RNase free water

Also known as: pcb

5% glucose, 0.5% benzyl alcohol in RNase free water

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory, dermatological, gastrointestinal, endocrine, hematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological, or psychiatric illness. Specifically:
• Subjects with any history of physician diagnosed and/or objective test-confirmed asthma, chronic obstructive pulmonary disease, pulmonary hypertension, reactive airway disease, or chronic lung condition of any etiology or who have experienced:
• Significant/severe wheeze in the past
• Respiratory symptoms including wheeze which have ever resulted in hospitalization.
• Known bronchial hyper-reactivity to viruses.
• History of thromboembolic, cardiovascular, or cerebrovascular disease
• History or evidence of diabetes mellitus
• Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine.
• History or evidence of autoimmune disease or known immunodeficiency of any cause.
• Other major diseases that, in the opinion of the investigator, could interfere with a subject completing the study and necessary investigations.
• Immunosuppression of any type.
• Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way (including loss of or alterations in smell or taste), a clinically significant history of epistaxis (large nosebleeds) within the last 3 months, nasal or sinus surgery within 6 months pre-screening.
• History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
• History or presence of alcohol addiction, or excessive use of alcohol. The subject has a history of consuming more than 7 units of alcoholic beverages per week for male subjects and more than 5 units for females (Note: one unit = 330 mL of beer, 110 mL of wine, or 28 mL of spirits), or has a history of alcoholism or drug/chemical/substance abuse within the past 2 years prior to screening.

Sponsors & Collaborators

• Interna Therapeutics Ltd.: lead

Study Sites (1)

HCRC Ein Karem

Jerusalem, Israel

Location

Related Links

• Translating the vision of macromolecule therapeutics into a druggable reality

MeSH Terms

Conditions

COVID-19; Infections

Interventions

C 76; Polychlorinated Biphenyls

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Dioxins and Dioxin-like Compounds; Organic Chemicals; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated

Study Officials

• Hagit Grimberg, PhD

  Interna Therapeutics Ltd.

  STUDY DIRECTOR

• Yoseph Caraco, MD

  HCRC Ein Karem, Israel

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 22, 2025
• First Posted: July 31, 2025
• Study Start: September 4, 2024
• Primary Completion: July 14, 2025
• Study Completion: August 30, 2025
• Last Updated: July 31, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)