A Clinical Trial of Immunobridging and Lot-to-lot Consistency of COVID-19 Vaccine (Ad5-nCoV) in Different Age Groups.

Study Overview
=================
Brief Summary
-----------------
The study is a single-center, randomized and double-blinded trial to evaluate the immunobridging between different manufacture scales, lot-to-lot consistency of the Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector)(Ad5-nCOV) in population 6-59 years of age. The immunobridging between different manufacture scales will be evaluated first, the immunobridging between different age groups will be evaluated second, the lot-to-lot consistency will be evaluated at last.

Official Title
-----------------
To Evaluate the Immunogenicity Bridging Between Different Manufacture Scales and Between Different Lots of Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) (Ad5-nCoV) in Population 6-59 Years of Age.

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

Intervention / Treatment
-----------------
* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.5ml
* Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 6-59 years of age at the time of enrollment; Able to provide consent or obtain consent from guardian to participate in the trial and sign an Informed Consent Form (ICF); Able and willing to complete all the scheduled study procedures during the whole study follow-up period; Axillary temperature ≤37.0℃; IgG ang IgM negative for Covid-19; Have not received any type of Covid-19 vaccines; No contact history of Covid-19; no travel history to medium and high risk regions and abroad in the past 21 days; Participants who are clinically determined to be healthy after checking medical history and physical examination are eligible to receive the product. Exclusion Criteria: Medical or family history of convulsions, epilepsy, encephalopathy, and psychosis disorders; History of allergies to any ingredient of Ad5-nCoV, history of serious allergic reactions to any vaccine, history of allergies and immune diseases; Women who are pregnant or lactating, positive urine pregnancy test or plan to become pregnant during the 12 months study period; Acute febrile diseases and infectious diseases, medical history of SARS (SARS-CoV-1); Serious cardiovascular diseases, such as arrhythmia, conduction block, myocardial infarction, severe hypertension and uncontrollable medications (on-site measurement for 18-59 years of age: systolic blood pressure ≥160mmHg, diastolic blood pressure ≥100mmHg), etc; Severe chronic diseases or with advanced stage conditions which cannot be controlled smoothly, such as diabetes, thyroid disease, etc; Congenital or acquired angioedema/neurological edema; Urticaria history within 1 year before receiving the study vaccine; Asplenia or functional aspleenia; Thrombocytopenia or other coagulation disorders (may cause contraindications for intramuscular injection); Trypanophobia； History of receiving immunosuppressant therapy, anti-allergic therapy, cytotoxic therapy, nebulized corticosteroid therapy in the past 6 months (not including corticosteroid spray treatment for allergic rhinitis, and surface corticosteroid treatment for acute non-complicated dermatitis); Prior administration of blood products in last 4 months; Received other investigational drugs within 1 month before the study; Prior administration of live attenuated vaccines within 1 month before the study; Prior administration of subunit or inactivated vaccines within 14 days before the study; Current anti-tuberculosis therapy; Medical history of Covid-19 disease/infection; Any condition that in the opinion of the investigators may interfere with the participants' compliance or evaluation of study objectives or informed consent (i.e. medical, psychological, social or other conditions, etc.).

Ages Eligible for Study
-----------------
Minimum Age: 6 Years
Maximum Age: 59 Years

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

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

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 50L Scale (Age 18-59)<br>Single dose of 0.5ml Ad5-nCoV containing 0.5E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.5ml<br>* Containing 0.5E10vp<br>|
| Experimental: 500L Scale (Age 18-59)<br>Single dose of 0.5ml Ad5-nCoV containing 0.5E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.5ml<br>* Containing 0.5E10vp<br>|
| Experimental: 800L Scale (Age 18-59)<br>Single dose of 0.5ml Ad5-nCoV containing 0.5E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.5ml<br>* Containing 0.5E10vp<br>|
| Experimental: 800L Scale Lot 1 (Age 13-17)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|
| Experimental: 800L Scale Lot 2 (Age 13-17)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|
| Experimental: 800L Scale Lot 3 (Age 13-17)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|
| Experimental: 800L Scale Lot 1 (Age 6-12)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|
| Experimental: 800L Scale Lot 2 (Age 6-12)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|
| Experimental: 800L Scale Lot 3 (Age 6-12)<br>Single dose of 0.3ml Ad5-nCoV containing 0.3E10 vp. | Biological: Recombinant Novel Coronavirus Vaccine (Adenovirus Type 5 Vector) 0.3ml<br>* Containing 0.3E10vp<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMT of anti SARS-CoV-2 specific neutralizing antibody | GMT of anti SARS-CoV-2 specific neutralizing antibody in all groups (wild type variants test). | 28 days after vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Seroconversion rate of SARS-CoV-2 neutralizing antibody | Seroconversion rate of anti SARS-CoV-2 specific neutralizing antibody (wild type variants test). | 28 days after vaccination | 
| GMI of SARS-CoV-2 neutralizing antibody | GMI of anti SARS-CoV-2 specific neutralizing antibody (wild type variants test). | 28 days after vaccination | 
| GMT of SARS-CoV-2 S protein RBD antibody | GMT of SARS-CoV-2 S protein RBD antibody measured by ELISA in all groups | 28 days after vaccination | 
| Seroconversion rate of SARS-CoV-2 S protein RBD antibody | Seroconversion rate of SARS-CoV-2 S protein RBD antibody measured by ELISA in all groups. | 28 days after vaccination | 
| GMI of SARS-CoV-2 S protein RBD antibody | GMI of SARS-CoV-2 S protein RBD antibody measured by ELISA in all groups. | 28 days after vaccination | 
| GMT of Ad5 vector neutralizing antibody | GMT of anti Ad5 vector neutralizing antibody responses post vaccination in all groups | 28 days after vaccination | 
| GMI of Ad5 vector neutralizing antibody | GMI of Ad5 vector neutralizing antibody responses post vaccination in all groups | 28 days after vaccination | 
| Stratified analysis on Ad5 vector neutralizing antibody | Stratified analysis based on the GMT of Ad5 vector neutralizing antibody responses post vaccination. | 28 days after vaccination | 
| Incidence of Adverse Reactions/Events (AE/AR) | The occurance of Adverse Reactions/Events within 30 minutes post vaccination | Within 30 minutes after vaccination | 
| Incidence of Adverse Reactions/Events (AE/AR) | The occurance of Adverse Reactions/Events (AE/AR) within 7 days post vaccination. | Within 0-7 days after vaccination | 
| Incidence of Adverse Reactions/Events (AE/AR) | The occurance of Adverse Reactions/Events (AE/AR) within 28 days post vaccination. | Within 0-28 days after vaccination | 
| Incidence of Serious Adverse Events (SAE) | Occurance of Serious Adverse Events (SAE) post vaccination. | Within 12 months after vaccination | 
| Incidence of Adverse Events of Special Interest (AESI) | Occurance of Adverse Events of Special Interest (AESI) post vaccination. | Within 12 months after vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COVID-19, Vaccine, Ad5, Immunobridging, Lot-to-lot consistency