To Evaluate Safety & Immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 for COVID-19 in Healthy Adults Received 2 Doses of BNT162b2

Study Overview
=================
Brief Summary
-----------------
To evaluate the safety and immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 as booster vaccine for COVID-19 in healthy adults who have received 2 doses of BNT162b2

Detailed Description
-----------------
This is a randomized, double-blinded, placebo-controlled study to evaluate the safety and immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 as booster vaccine for COVID-19 in healthy adults who have received 2 doses of BNT162b2. Each subject will receive 2 vaccinations or matching placebo 3 weeks apart.

Official Title
-----------------
A Randomized, Double-blinded, Placebo-controlled Study to Evaluate the Safety and Immunogenicity of DelNS1-2019-nCoV-RBD-OPT1 as Booster Vaccine for COVID-19 in Healthy Adults Who Have Received 2 Doses of BNT162b2

Conditions
-----------------
Covid19

Intervention / Treatment
-----------------
* Biological: DelNS1-2019-nCoV-RBD-OPT1
* Biological: Matching placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Informed Consent: The subject (or the subject's legally acceptable representative, if applicable) must be capable of giving written informed consent and, prior to the commencement of any study-specific procedure, must sign an ICF indicating the consent on the subject's voluntary participation in the study and compliance with the requirements and restrictions listed on the ICF. BNT162b2 Vaccination Status: The subject must have received 2 doses of BNT162b2 in Hong Kong, with the second dose completed at least 180 days prior to the first vaccination. Gender and Age: Male or female, at the age of ≥ 18 and ≤ 75 on the day of signing the ICF. Body Weight and BMI: Body weight ≥ 45 kg and BMI ≥ 18.5 kg/m2 and < 25 kg/m2 at screening and baseline. Medical Conditions or Diagnoses: Existence of all of the following medical conditions or diagnoses: Generally in good health with no clinically significant abnormality, as determined by medical history, physical examination, 12-lead ECG and clinical laboratory tests at screening and baseline; Normal vital signs at screening and baseline, as defined by: Body (tympanic) temperature ≤ 37.5 oC; Resting pulse rate ≥ 50 and ≤ 100 bpm; and DBP ≥ 50 and ≤ 90 mmHg and SBP ≥ 90 and ≤ 140 mmHg. Contraception: Willingness and agreement to undertake measures to avoid pregnancy of the subject or the subject's sexual partner(s) as detailed below: A female subject who is a woman of childbearing potential (WOCBP) must be willing and agree to remain abstinent or practise at least one effective contraceptive method from at least 30 days prior to the first vaccination until 60 days after the second vaccination; A male subject (i) who is sexually active with a WOCBP (except who is permanently sterile by bilateral orchiectomy or vasectomy) must be willing and agree to remain abstinent or practise at least one effective contraceptive method from the first vaccination until 60 days after the second vaccination; and (ii) must be willing and agree to refrain from sperm donation during the aforesaid period. Breastfeeding: A female subject must be willing and agree to avoid engagement in breastfeeding at any time from the first vaccination until 60 days after the second vaccination. Blood Donation: Willingness and agreement to avoid blood donation from screening to the end of the period of participation in this study. Exclusion Criteria: Medical History: History of any of the following diseases or conditions: COVID-19; SARS; Any significant respiratory diseases (e.g. COPD, asthma); Any significant cardiovascular disease (e.g. angina, cardiac arrhythmias); Blood dyscrasias or any significant disorder of coagulation; Any chronic liver disease (e.g. autoimmune hepatitis and cirrhosis); Any chronic infection (e.g. hepatitis B, hepatitis C and HIV); Any malignant neoplastic disease; Encephalopathy, neuropathy or unstable central nervous system (CNS) pathology; Any psychiatric disorder, psychotic disorder, major affective disorder or suicidal ideation; Any immunodeficiency or autoimmune disease; Any severe allergic reaction (e.g. anaphylaxis) to any vaccine or substance, which requires hospitalization or emergency medical care; Any nasal septal defect, cleft palate, nasal polyps or other nasal abnormality that might affect vaccine administration; History of alcohol or illicit drug abuse, or used any illicit drug within 6 months prior to screening. Medical Conditions or Diagnoses: Existence of any of the following medical conditions or diagnoses: Positive serum pregnancy test at screening or positive urine pregnancy test at baseline (for WOCBP); IgE level > 1,000 IU/ml at screening; Positive SARS-CoV-2 test result in deep throat saliva (DTS) within 4 days prior to the first vaccination; Positive HIV test result at screening; Positive HBsAg test result at screening; Positive HCV antibody test result at screening; Positive urine drug screen test result or positive blood alcohol test result at screening or baseline; Clinically significant abnormality of T3, T4 or TSH at screening; Clinically significant abnormality of PT (INR) or aPTT at screening. Prior/Concomitant Interventions: Use of or undergoing any of the following prior or concomitant medications, therapies or interventions: Any COVID-19 or coronavirus vaccine at any time prior to the first vaccination, except BNT162b2 or planned use of any such vaccine throughout the study; Any vaccine other than COVID-19 or coronavirus vaccines within 28 days prior to the first vaccination, or planned use of any such vaccine up to 28 days after the second vaccination; Any immune-modifying medication/therapy (e.g. immunomodulator and immunosuppressant) within 6 months prior to the first vaccination, or planned use of any such medication/therapy throughout the study; Any blood product (including blood transfusion) or immunoglobulin within 3 months prior to the first vaccination, or planned use of any such therapy throughout the study; Any anticoagulation medication within 28 days prior to the first vaccination, or planned use of any such medication up to 28 days after the second vaccination; Any psychotropic medication within 28 days prior to the first vaccination, or planned use of any such medication up to 28 days after the second vaccination; Regular use of any inhaled/nebulized corticosteroid; Any intranasal preparation within 48 hours prior to the first vaccination, or planned use of any such preparation up to 48 hours after the second vaccination; Any influenza antiviral medication within 48 hours prior to the first vaccination, or planned use of any such medication up to 14 days after the second vaccination; Any prescription or over-the-counter medication within 7 days prior to the first vaccination, unless with the investigator's approval; Donated ≥ 450 ml of blood within 28 days prior to the first vaccination; Prior nasal surgery or nasal cauterization. Prior/Concurrent Clinical Study: Prior or concurrent participation in any other clinical study, including: Prior or current participation in another COVID-19 vaccine study; Prior participation in any interventional clinical study and use of any investigational intervention within 90 days prior to the first vaccination; Concurrent participation or plan for participation in another interventional clinical study during participation in this study. Other Significant Medical Conditions: Any clinically significant concomitant disease or condition that, in the reasonable opinion of the investigator, may interfere with the subject's participation in this study or pose an unacceptable safety risk for the subject's participation in this study. Special Conditions: Existence of any of the following special conditions: Close contact with anyone known to have COVID-19 within 30 days prior to the first vaccination; Travelled outside Hong Kong within 14 days prior to the first vaccination; Planned to travel outside Hong Kong at any time during the period from screening to Day 50(±3) visit.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Test Product<br>DelNS1-2019-nCoV-RBD-OPT1 virus titre at not less than 6.3 lg CCID50/dose, 2 doses 3 weeks apart, intranasal administration | Biological: DelNS1-2019-nCoV-RBD-OPT1<br>* Influenza Virus Vector COVID-19 Vaccine for Intranasal Spray<br>|
| Placebo Comparator: Reference Product<br>Matching placebo, 2 doses 3 weeks apart, intranasal administration | Biological: Matching placebo<br>* Solution for Intranasal Spray<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reactogenicity | Occurrence of solicited local events (nasal irritation, sneezing, nasal congestion, cough, sore throat, change in smell, change in taste, change in vision and eye pain) and solicited systemic events (fever, headache, malaise, myalgia, joint pain, nausea, vomiting, diarrhea, abdominal pain, chills and sweating) for a 14-day period after each vaccination | Day 1 to 15 and Day 22 to 36 | 
| Adverse Events | Occurrence of unsolicited AEs, Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs) | Day 1 to Day 202(±7) | 
| Neutralizing Antibodies in Serum against Live SARS-CoV-2 Measured by Neutralization Assay | Measurement of neutralizing antibody levels by microneutralization (MN) assay in serum samples | Day 1(pre-dose), 22(pre-dose), 36(+2) and 50(±3) | 
| Binding Antibodies in Serum against SARS-CoV-2 RBD Measured by CMIA | Measurement of binding antibody responses by chemiluminescent microparticle immunoassay (CMIA) in serum samples | Day 1(pre-dose), 22(pre-dose), 36(+2) and 50(±3) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| T-cell Responses against SARS-CoV-2 Spike Peptide Measured by ELISpot | Enumeration of antigen-specific T cells by IFN gamma ELISpot assay in serum samples | Day 1(pre-dose), 22(pre-dose), 36(+2) and 50(±3) | 
| Total Ig Antibodies in Mucosal Secretion against SARS-CoV-2 RBD Measured by ELISA | Measurement of total Ig antibody levels in saliva samples | Day 1(pre-dose), 4(+1), 22(pre-dose), 25(+1), 36(+2) and 50(±3) |