A Clinical Trial of A COVID-19 Vaccine Named Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)

Study Overview
=================
Brief Summary
-----------------
This study is a randomized, double-blind, placebo -controlled IIb clinical trial, in order to evaluate the safety and immunogenicity of Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) in people 6 years old and above and .

Detailed Description
-----------------
This is a phase IIb clinical trial to evaluate safety and immuogenicity of Ad5-nCoV developed by Cansino and Beijing Institute of Biotechnology in health people aged 6 years old and above. The study will be double-blind, placebo-controlled trial with participants randomly allocated 2:1 to placebo and experimental vaccine . The immunization schedule is two doses intramuscular injections (deltoid).

Official Title
-----------------
A Randomized, Double-blind, Placebo -Controlled Phase IIb Clinical Trial to Evaluate the Safety and Immunogenicity of Ad5-nCoV in Person 6 Years of Age and Older and Those Who Have Previously Been Vaccinated With Ad5-EBOV

Conditions
-----------------
COVID-19

Intervention / Treatment
-----------------
* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)
* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged 18 to 55 years old in MID group; aged 6-17 years old in MIN group; aged 56 years and above in OLD group; aged in EBO group is not limited. Able to understand the content of informed consent and willing to sign the informed consent Able and willing to complete all the secluded study process during the whole 6 months study follow-up period. Negative in HIV diagnostic test. Negative in serum antibodies (IgG and IgM) screening of COVID-19. Axillary temperature ≤37.0°C. General good health as established by medical history and physical examination. Exclusion Criteria: Family history of seizure, epilepsy, brain or mental disease Subject allergic to any component of the investigational vaccine, or a more severe allergic reaction and history of allergies in the past. Woman who is pregnant, breast-feeding or positive in β-HCG (human chorionic gonadotropin) pregnancy test (urine) on day of enrollment, or become pregnant during the next 6 months Any acute fever disease or infections. History of SARS Major congenital defects or not well-controlled chronic illness, such as asthma, diabetes, or thyroid disease. Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension without controllable drugs, etc. Hereditary angioneurotic edema or acquired angioneurotic edema Urticaria in last one year No spleen or functional spleen. Platelet disorder or other bleeding disorder may cause injection contraindication Faint at the sight of needles. Prior administration of immunodepressant or corticosteroids, antianaphylaxis treatment, cytotoxic treatment in last 6 months. Prior administration of blood products in last 4 months Prior administration of other research medicines in last 1 month Prior administration of attenuated vaccine in last 1 month Prior administration of inactivated vaccine in last 14 days Current anti-tuberculosis prophylaxis or therapy According to the judgement of investigator,various medical, psychological, social or other conditions, those could affect the subjects to sign informed consent.

Ages Eligible for Study
-----------------
Minimum Age: 6 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: MID A<br>20 participants(18-49), Ad5-nCoV , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular other name:Ad5-nCoV<br>|
| Placebo Comparator: MID B<br>10 participants(18-49), Ad5-nCoV-placebo , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo<br>* Intramuscular other name:Ad5-nCoV<br>|
| Experimental: MIN A<br>100 participants(6-17), Ad5-nCoV , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular other name:Ad5-nCoV<br>|
| Placebo Comparator: MIN B<br>50 participants(6-17), Ad5-nCoV-placebo , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo<br>* Intramuscular other name:Ad5-nCoV<br>|
| Experimental: OLD A<br>100 participants(56 years of age and above), Ad5-nCoV , two doses(Low dose), Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular other name:Ad5-nCoV<br>|
| Experimental: OLD B<br>100 participants(56 years of age and above), Ad5-nCoV , two doses(Middle dose), Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular other name:Ad5-nCoV<br>|
| Placebo Comparator: OLD C<br>50 participants(56 years of age and above), Ad5-nCoV-placebo , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo<br>* Intramuscular other name:Ad5-nCoV<br>|
| Experimental: EBOV A<br>34 participants, Ad5-nCoV , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)<br>* Intramuscular other name:Ad5-nCoV<br>|
| Placebo Comparator: EBOV B<br>17 participants, Ad5-nCoV , two doses, Intramuscular administration | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) -placebo<br>* Intramuscular other name:Ad5-nCoV<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety indexes of adverse reactions | Occurrence of adverse reactions post vaccination | within 14 days post each vaccination | 
| Immunogencity indexes of GMT | Evaluate the Geometric mean titer (GMT) of IgG antibody | Day 28 post the second vaccination | 
| Immunogencity indexes of neutralizing antibody | Evaluate the Geometric mean titer (GMT) of neutralizing antibody | Day 28 post the second vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety indexes of adverse events | Occurrence of adverse reactions post-vaccination | Day 0-7,0-14,0-28 post each vaccination | 
| Safety indexes of Hematological examination measures（Hemoglobin, WBC） | Occurrence of abnormal changes of Hematological examination indexes(only fit for MID and sentinel group) | pre-vaccination, day 4 post each vaccination | 
| Safety indexes of Blood routine measures(ALT, AST) | Occurrence of abnormal changes of lBlood routine indexes (only fit for MID and sentinel group) | pre-vaccination, day 4 post each vaccination | 
| Safety indexes of SAE | Occurrence of serious adverse events post-vaccination | Within 6 months post the second vaccination | 
| Immunogencity indexes of GMT | Evaluate the Geometric mean titer of IgG antibody | Day 28 post the first vaccination, pre the second vaccination ,Month 6 post the second vaccination | 
| Immunogencity indexes of neutralizing antibody | Evaluate the Geometric mean titer (GMT) of neutralizing antibody | Day 28 post the first vaccination, pre the second vaccination ,Month 6 post the second vaccination | 
| Immunogencity indexes of cellular immune | Number of cell-mediated immune response against SARS-CoV-2（IL-2） | Day 28 post the first vaccination, pre and day 28 post the second vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Vaccine, Ad5, Safety, Immunogencity, SARS-CoV-2, Adenovirus Vector