A Booster Dose of Ad5-EBOV in Healthy Adults After Primary Immunization

Study Overview
=================
Brief Summary
-----------------
Since its first outbreak occurred in 1976, Zaire Ebola virus have been associated with 14 outbreaks reported up to 2014. The Zaire Ebola virus in 2014 causing the most serious outbreak was considered to be a new epidemic strain, with GP homology of the gene was only 97.6%, compared to the GP gene of the strain in 1976. This investigational Ad5-EBOV vaccine was developed according to the 2014 epidemic Zaire strain and formulated as freeze-dry products which could be stored at 4℃. In 2014, a single center, double-blind, placebo control, dose-escalation phase 1 clinical trial was performed in Taizhou, China. Our findings show that the Ad5-EBOV vaccine is safe and robustly immunogenic. One shot of the high dose vaccine could mount glycoprotein-specific humoral and T-cell response against Ebola virus in 14 days. The investigators intent to evaluate the safety and immunogenicity of a booster dose of the recombinant Ebola adenovirus vector vaccine (Ad5-EBOV) in healthy adults after primary immunization in this add in study. The investigators expect that the boosting immunization with a same vaccine for primary immunization is possible and could confer a longer-lived protection when needed. The phase I trial has been unblind 28 days after the primary vaccination, but all the subjects are still kept blind as well as the laboratory staffs. Therefore, this booster vaccination trial will be conduct in single blind.

Official Title
-----------------
Safety and Immunogenicity of a Booster Dose of the Recombinant Ebola Adenovirus Vector Vaccine (Ad5-EBOV) in Healthy Adults After Primary Immunization

Conditions
-----------------
Ebola Virus Disease

Intervention / Treatment
-----------------
* Biological: 4×10^10vp/1ml Ebola Zaire vaccine (Ad5-EBOV)
* Biological: 1.6×10^11vp/2ml Ebola Zaire vaccine (Ad5-EBOV)
* Biological: placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Participants who enrolled in the initial study, and completed the primary vaccination. Able to understand the content of the additional informed consent and willing to sign the additional informed consent for the boosting study Able and willing to complete a one-month follow-up. HIV negative Axillary temperature ≤37.0°C on the day of enrollment General good health as established by medical history and physical examination. Exclusion Criteria: New occurrence of any of the following situation after the primary vaccination: Subject that has a medical history of any of the following: allergic history of any vaccination or drugs, or allergic to any ingredient of the Ad5-EBOV vaccine, such as mannitol Woman who become pregnant after the primary vaccination or is positive in β-HCG (human chorionic gonadotropin) pregnancy test (urine) on day of enrollment for the boosting study Any acute fever disease or infections in last 7 days Not well-controlled chronic illness, such as asthma, diabetes, or thyroid disease Hereditary angioneurotic edema or acquired angioneurotic edema Urticaria in last 6 months Asplenia or functional asplenia Platelet disorder or other bleeding disorder may cause injection contraindication Faint at the sight of blood or 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 Any condition that in the opinion of the investigators may interfere with the evaluation of study objectives

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low dose group<br>4×10^10vp/1ml Ebola Zaire vaccine (Ad5-EBOV) | Biological: 4×10^10vp/1ml Ebola Zaire vaccine (Ad5-EBOV)<br>* one dose, 4×10^10vp/1ml per dose<br>|
| Experimental: high dose group<br>1.6×10^11vp/2ml Ebola Zaire vaccine (Ad5-EBOV) | Biological: 1.6×10^11vp/2ml Ebola Zaire vaccine (Ad5-EBOV)<br>* two doses, 0.8×10^11vp/1ml per dose, with one dose to each arm at the same time<br>|
| Placebo Comparator: placebo group<br>placebo | Biological: placebo<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse reactions after vaccination | Occurrence of adverse reactions within 7 days after vaccination with the Ebola Zaire vaccine (Ad5-EBOV) | within 7 days after the boosting | 
| Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) | Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) as measured by ELISA | 28 days after the boosting | 
| Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) | Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) | 28 days after the boosting | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of adverse events after the vaccination | Occurrence of adverse events within 28 days after vaccination with the Ebola Zaire vaccine (Ad5-EBOV) | within 28 days after the boosting | 
| Occurrence of serious adverse events after the vaccination | Occurrence of serious adverse events within 28 days after the vaccination with the Ebola Zaire vaccine (Ad5-EBOV) | within 28 days after the boosting | 
| Serum neutralizing antibody against the Ad5-vector | Serum neutralizing antibody against the Ad5-vector 28 days after the boosting | 28 days after the boosting | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Safety, immunogenicity, Ebola vaccine, boosting