A Phase I Clinical Trial to Evaluate the Ebola Adenovirus Vector Vaccine (Ad5-EBOV) in Healthy Adults.

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℃. This is a single center, double-blind, placebo control, dose-escalation phase 1 clinical trial. This study will determine the safety and side-effect profile, and immunogenicity of an investigational Ad5-EBOV vaccine.

Official Title
-----------------
A Phase 1 Double-blind, Dose-escalation, Clinical Trial to Evaluate the Safety, Tolerability and Immunogenicity of the Ebola Adenovirus Vector Vaccine (Ad5-EBOV) in Healthy Adults in China

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

Intervention / Treatment
-----------------
* Biological: Low dose Ebola Zaire vaccine (Ad5-EBOV)
* Biological: High dose Ebola Zaire vaccine (Ad5-EBOV)
* Biological: placebo (one dose)
* Biological: placebo (two doses)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Aged between 18 and 60 years. 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 study follow-up period (about 6 months). A body mass index (BMI) <35 Hemoglobin 110-150g/L for female, and 120-160g/L for male. White blood cells (WBC) 4.0-10.0×109 cells/L Total lymphocyte Count 0.8-4.5×109 cells/L Platelets 100-300×109 cells/L Alanine aminotransferase (ALT) 0-40U/L Serum creatinine 44-106μmol/L Partial thromboplastin time (PTT) 20-40 seconds Prothrombin time (PT) 10-14 seconds Negative in HIV diagnostic blood test Axillary temperature ≤37.0°C on the day of enrollment General good health as established by medical history and physical examination. Exclusion Criteria: Family history of seizure, epilepsy, brain or mental disease 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 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 in last 7 days Major congenital defects or not well-controlled chronic illness, such as asthma, diabetes, or thyroid disease Hereditary angioneurotic edema or acquired angioneurotic edema Urticaria in last one year 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
-----------------
No

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

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo group (one shot)<br>one dose | Biological: placebo (one dose)<br>* placebo, one doses<br>|
| Placebo Comparator: Placebo group (two shots)<br>two doses, with one dose to each arm at a same time. | Biological: placebo (two doses)<br>* placebo, two doses, with one dose to each arm at a same time.<br>|
| Experimental: Low dose vaccine group<br>one dose, low dose Ebola Zaire vaccine (Ad5-EBOV) | Biological: Low dose Ebola Zaire vaccine (Ad5-EBOV)<br>* one dose, Low dose Ebola Zaire vaccine (Ad5-EBOV)<br>|
| Experimental: High dose vaccine group<br>two doses, high dose, with one dose to each arm at a same time | Biological: High dose Ebola Zaire vaccine (Ad5-EBOV)<br>* two doses, High dose Ebola Zaire vaccine (Ad5-EBOV), with one dose to each arm at a same time.<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 vaccination | 
| 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 vaccination | 
| Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV). | Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) as measured by intracellular cytokine staining assays (ICS) | 28 days after the vaccination | 

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 vaccination | 
| Changes of the laboratory examinations after vaccination. | Changes of the laboratory examinations after vaccination with the Ebola Zaire vaccine (Ad5-EBOV) on day 3, 14 and 28. | day 0-28 after the vaccination | 
| Occurrence of serious adverse events after the vaccination. | Occurrence of serious adverse events within 6 months after the vaccination with the Ebola Zaire vaccine (Ad5-EBOV). | within 6 months after the vaccination | 
| Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV). | Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 168 as measured by ELISA. | 168 days after the vaccination | 
| Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV). | Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 168 as measured by intracellular cytokine staining assays (ICS). | 168 days after the vaccination | 
| Anti-adenovirus neutralizing antibody responses to the Ebola Zaire vaccine (Ad5-EBOV). | Anti-adenovirus neutralizing antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 168. | 168 days after the vaccination | 

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