Efficacy and Safety of Nasal Spray Solution Containing Human IgG1 Anti-COVID-19 Antibody Cocktail

Study Overview
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Brief Summary
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Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail is a medical device innovated to provide the dual-action physical barrier on nasal mucosa that aids the natural defence in which the mucus layer is fortified by a steric barrier-forming agent HPMC and invading viral particles of all major SARS-CoV-2 VOCs, including Delta and Omicron, are locally trapped and blocked from entering the cells by the highly-specific human IgG1 anti-SARS-CoV-2 monoclonal antibody cocktail.

Detailed Description
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The transmission of SARS-CoV-2 through inhalation results in the nasal cavity and nasopharynx being the primary entry point of the virus and containing the highest viral load in the body during the virus incubation period. Recently, the administration of vaccines and agents via a nasal route has gained a lot of momentum because it takes advantage of the direct delivery of an agent to the site of primary infection. The local defence system, especially antibody-mediated immunity at the nasal epithelium, is crucial for COVID-19 prevention. However, people who responded to the vaccination against COVID-19 typically maintain sufficient local antibody levels in the nasal cavity for only a short period; hence a repeated boosting strategy is required to control the rate of SARS-CoV-2 breakthrough infection. In addition, the new VOCs such as Omicron are known to escape vaccine immunity; therefore, an innovative approach is needed in this unprecedented situation Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail is a medical device innovated to provide the dual-action physical barrier on nasal mucosa that aids the natural defence in which the mucus layer is fortified by a steric barrier-forming agent HPMC and invading viral particles of all major SARS-CoV-2 VOCs, including Delta and Omicron, are locally trapped and blocked from entering the cells by the highly-specific human IgG1 anti-SARS-CoV-2 monoclonal antibody cocktail.

Official Title
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A Phase I Double-blind, Randomized, Placebo-controlled Study to Evaluate Safety of Hypromellose-based Nasal Spray Solution Containing Human IgG1 Anti-SARS-CoV-2 Antibody Cocktail in Healthy Volunteers

Conditions
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SARS CoV 2 Infection, SARS-CoV-2 Acute Respiratory Disease

Intervention / Treatment
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* Device: Human IgG1 anti-SARS-CoV-2 antibody cocktail
* Device: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion criteria Male or female, ≥ 18 and ≤ 50 years of age with BMI ≥ 18 and ≤ 30 kg/m2 Healthy as defined by: No previous clinically significant disease and surgery within 4 weeks prior to dosing. No previous sinus and nasal septum surgery or radiotherapy No evidence of clinically significant history of neurological, endocrine, cardiovascular, pulmonary, hematological, immunologic, psychiatric, gastrointestinal, renal, hepatic, and metabolic disease which the Investigator believes may be detrimental to the study or its aims. No evidence of febrile or infectious disease within 1 week prior to dosing. Have received at least 2 doses of COVID-19 vaccine. Have no history of close contact with COVID-19 patients within 2 weeks before enrolment Have negative result of COVID-19 test using RT-PCR method using sample collected from nasopharyngeal or nasal or oropharyngeal swab within 72 hours before sinusoscopy Provide signed written informed consent prior to the initiation of any study-specific procedures. Willing and able to comply with the requirements of the protocol and be available for the planned duration of the trial. Exclusion criteria Any clinically significant abnormality at physical examination at screening or enrolment Vital sign abnormalities (systolic blood pressure lower than 90 or over 140 mmHg, diastolic blood pressure lower than 40 or over 90 mmHg, heart rate less than 40 or over 100 bpm, respiratory rate less than 10 or over 22 bpm, oral temperature less than 35.5°C or over 37.5°C) at screening. Positive urine pregnancy test for women or women who are breast feeding History of COVID-19 infection within 3 months before enrollment History of allergic reactions or hypersensitivity to any excipients of the study products. Use any nasal product use within 14 days prior to the first dosing History of pulmonary infiltrate or pneumonia within 6 months before the screening visit. Signs or symptoms of respiratory tract abnormalities such as allergies or chronic obstructive pulmonary disease. History or signs of chronic allergic rhinitis that may interfere with study procedures and/or interpretation of local adverse events.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

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: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Tolerability and safety of the study product will be evaluated when given 3 times a day for 7 days in 36 healthy volunteers.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human IgG1 anti-SARS-CoV-2 antibody cocktail<br>Subjects will receive the Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail (i.e., applied into both nostrils by spraying two times per nostril) 3 times a day from Day 1 to Day 7. Each day the study products will be self-administered at 8 am, 2 pm, and 8 pm. | Device: Human IgG1 anti-SARS-CoV-2 antibody cocktail<br>* Hypromellose-based nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail<br>|
| Placebo Comparator: Placebo<br>Subjects will receive the Normal saline solution (0.9% NaCl) nasal spray solution containing human IgG1 anti-SARS-CoV-2 antibody cocktail (i.e., applied into both nostrils by spraying two times per nostril) 3 times a day from Day 1 to Day 7. Each day the study products will be self-administered at 8 am, 2 pm, and 8 pm. | Device: Placebo<br>* Normal saline<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Tolerability and safety of the study product as measured by treatment emergent adverse events (TEAEs) | 1 Day | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of inhibition against SAR-CoV-2 in the nasal fluid | SARS-CoV-2 inhibition property of the study product as measured by the percentage of inhibition against SAR-CoV-2 in the nasal fluid before and after the study product application via cPass™ SARS-CoV-2 Neutralization Antibody Detection Kit | 14 Days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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SARS-CoV-2, SARS-CoV-2 inhibition, Nasal Spray, Anti-SARS-CoV-2, Antibody Cocktail