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

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

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.

Study Overview

• Status: Completed
• Conditions: Ebola Virus Disease
• Intervention / Treatment: Biological: placebo (one dose); Biological: placebo (two doses); Biological: Low dose Ebola Zaire vaccine (Ad5-EBOV); Biological: High dose Ebola Zaire vaccine (Ad5-EBOV)

• Study Type: Interventional
• Enrollment (Actual): 120
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Jiangsu
    • Taizhou, Jiangsu, China
      • Phase 1 vaccine clinical trial center of Jiangsu Provincial Center for Disease Control and Prevention

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo group (one shot); one dose	Biological: placebo (one dose); placebo, one doses
Placebo Comparator: Placebo group (two shots); two doses, with one dose to each arm at a same time.	Biological: placebo (two doses); placebo, two doses, with one dose to each arm at a same time.
Experimental: Low dose vaccine group; one dose, low dose Ebola Zaire vaccine (Ad5-EBOV)	Biological: Low dose Ebola Zaire vaccine (Ad5-EBOV); one dose, Low dose Ebola Zaire vaccine (Ad5-EBOV)
Experimental: High dose vaccine group; two doses, high dose, with one dose to each arm at a same time	Biological: High dose Ebola Zaire vaccine (Ad5-EBOV); two doses, High dose Ebola Zaire vaccine (Ad5-EBOV), with one dose to each arm at a same time.

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes of the laboratory examinations after vaccination.	Changes of the laboratory examinations after vaccination with the Ebola Zaire vaccine (Ad5-EBOV) at day 168.	day 168 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 3, 7, 14, 56 and 112 as measured by ELISA.	3-112 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 3, 7, 14, 56 and 112.	3-56 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 7, 14, 56 and 112 as measured by intracellular cytokine staining assays (ICS).	day 7-112 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 0, 28 and 168 as measured by ELISpot.	day 0-168 after the vaccination

Collaborators and Investigators

• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Collaborators: Beijing Institute of Biotechnology; Tianjin Cansino Biotechnology Inc

Publications and helpful links

General Publications

• Li JX, Hou LH, Meng FY, Wu SP, Hu YM, Liang Q, Chu K, Zhang Z, Xu JJ, Tang R, Wang WJ, Liu P, Hu JL, Luo L, Jiang R, Zhu FC, Chen W. Immunity duration of a recombinant adenovirus type-5 vector-based Ebola vaccine and a homologous prime-boost immunisation in healthy adults in China: final report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet Glob Health. 2017 Mar;5(3):e324-e334. doi: 10.1016/S2214-109X(16)30367-9. Epub 2016 Dec 23.
• Zhu FC, Hou LH, Li JX, Wu SP, Liu P, Zhang GR, Hu YM, Meng FY, Xu JJ, Tang R, Zhang JL, Wang WJ, Duan L, Chu K, Liang Q, Hu JL, Luo L, Zhu T, Wang JZ, Chen W. Safety and immunogenicity of a novel recombinant adenovirus type-5 vector-based Ebola vaccine in healthy adults in China: preliminary report of a randomised, double-blind, placebo-controlled, phase 1 trial. Lancet. 2015 Jun 6;385(9984):2272-9. doi: 10.1016/S0140-6736(15)60553-0. Epub 2015 Mar 25.

Study record dates

Study Major Dates

• Study Start: December 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): July 1, 2015

Study Registration Dates

• First Submitted: December 22, 2014
• First Submitted That Met QC Criteria: December 22, 2014
• First Posted (Estimate): December 25, 2014

Study Record Updates

• Last Update Posted (Estimate): August 28, 2015
• Last Update Submitted That Met QC Criteria: August 27, 2015
• Last Verified: August 1, 2015

More Information

Terms related to this study

• Keywords: Safety,immunogenicity,Ebola
• Additional Relevant MeSH Terms: RNA Virus Infections; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Virus Diseases; Hemorrhagic Fever, Ebola; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: JSVCT020