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

• ClinicalTrials.gov Identifier: NCT02326194
• Recruitment Status: Completed
• First Posted: December 25, 2014
• Last Update Posted: August 28, 2015
• Sponsor: Jiangsu Province Centers for Disease Control and Prevention
• Collaborators: Beijing Institute of Biotechnology; Tianjin Cansino Biotechnology Inc
• Information provided by (Responsible Party): Fengcai Zhu, Jiangsu Province Centers for Disease Control and Prevention

Tracking Information

• First Submitted Date: December 22, 2014
• First Posted Date: December 25, 2014
• Last Update Posted Date: August 28, 2015
• Study Start Date: December 2014
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: December 22, 2014)

• Occurrence of adverse reactions after vaccination. [ Time Frame: within 7 days after the vaccination ]
  Occurrence of adverse reactions within 7 days after vaccination with the Ebola Zaire vaccine (Ad5-EBOV).
• Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: 28 days after the vaccination ]
  Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) as measured by ELISA.
• Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: 28 days after the vaccination ]
  Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) as measured by intracellular cytokine staining assays (ICS)

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 22, 2014)

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

• Original Secondary Outcome Measures: Same as current

Current Other Pre-specified Outcome Measures (submitted: December 22, 2014)

• Changes of the laboratory examinations after vaccination. [ Time Frame: day 168 after the vaccination ]
  Changes of the laboratory examinations after vaccination with the Ebola Zaire vaccine (Ad5-EBOV) at day 168.
• Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: 3-112 days after the vaccination ]
  Specific anti-EBOV antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 3, 7, 14, 56 and 112 as measured by ELISA.
• Anti-adenovirus neutralizing antibody responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: 3-56 days after the vaccination ]
  Anti-adenovirus neutralizing antibody responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 3, 7, 14, 56 and 112.
• Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: day 7-112 after the vaccination ]
  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).
• Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV). [ Time Frame: day 0-168 after the vaccination ]
  Specific T cell immune responses to the Ebola Zaire vaccine (Ad5-EBOV) at day 0, 28 and 168 as measured by ELISpot.

• Original Other Pre-specified Outcome Measures: Same as current

Descriptive Information

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

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.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Triple (Participant, Care Provider, Investigator); Primary Purpose: Prevention
• Condition: Ebola Virus Disease

Intervention

• Biological: Low dose Ebola Zaire vaccine (Ad5-EBOV)
  one dose, Low dose Ebola Zaire vaccine (Ad5-EBOV)
• 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.
• Biological: placebo (one dose)
  placebo, one doses
• Biological: placebo (two doses)
  placebo, two doses, with one dose to each arm at a same time.

Study Arms

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

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: December 22, 2014): 120
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: July 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 60 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT02326194
• Other Study ID Numbers: JSVCT020
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Fengcai Zhu, Jiangsu Province Centers for Disease Control and Prevention
• Study Sponsor: Jiangsu Province Centers for Disease Control and Prevention

Collaborators

• Beijing Institute of Biotechnology
• Tianjin Cansino Biotechnology Inc

• Investigators: Not Provided
• PRS Account: Jiangsu Province Centers for Disease Control and Prevention
• Verification Date: August 2015