A Study to Assess New Ebola Vaccines, cAd3-EBO Z and MVA-BN® Filo

Phase 1

Completed

• Conditions: Ebola; Ebola Zaire
• Interventions: Biological: cAd3-EBO Z at 5 x 10^10 vp; Biological: cAd3-EBO Z at 1 x 10^10 vp; Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Biological: 4.4x10^8 TCID50s MVA-BN® Filo; Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Biological: 4.4 x 10^7 TCID50s MVA-BN® Filo

• Registration Number: NCT02240875
• Lead Sponsor: University of Oxford

Brief Summary

The purpose of this study is to assess two new Ebola vaccines: cAd3-EBO Z at 3 different doses, and a second vaccine, MVA-BN® Filo, at 3 different doses. The study will enable us to assess the safety of the vaccines and the extent of the immune response in healthy volunteers. The investigators will do this by giving volunteers a either one or two vaccinations, doing blood and saliva tests and collecting information about any symptoms that occur after vaccination. This is the first trial to use either of these vaccines in humans. We plan to recruit a total of 92 volunteers to be vaccinated.

Detailed Description

Long- term immunology follow-up: In order to assess the durability of vaccine induced immunogenicity, all vaccinated subjects will be invited back to attend a maximum of 3 further optional follow up visits at least 12 months after their final vaccination. The 3 visits will have a minimum interval of 3 months between them, and the final visit must take place no longer than 12 months after the first optional visit.

Volunteers who attend these visits will be asked about occurrence of any SAEs during the intervening period. SAE data for this period will not be collected in those volunteers who decline to attend these additional visits.

Study Timeline

• Study First Submitted: 2014-09-10
• Study First Submitted QC: 2014-09-15
• Study First Posted: 2014-09-16
• Study Start: 2014-09-17
• Primary Completion: 2017-08-22
• Study Completion: 2017-08-22
• Status Verified: 2018-07
• Last Update Submitted: 2018-07-04
• Last Update Posted: 2018-07-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 91

Inclusion Criteria

• Healthy adults aged 18 to 50 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• Willing to allow the investigators to discuss the volunteer's medical history with their general practitioner (GP)
• For females only, willingness to practice continuous effective contraception during the study and a negative pregnancy test on the day(s) of screening and vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent

Exclusion Criteria

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
• Prior receipt of an investigational Ebola or Marburg vaccine, a chimpanzee adenovirus vectored vaccine or any other investigational vaccine likely to impact on interpretation of the trial data
• Receipt of any live, attenuated vaccine within 28 days prior to enrolment
• Receipt of any subunit or killed vaccine within 14 days prior to enrolment
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, (e.g. egg products) including urticaria, respiratory difficulty or abdominal pain
• Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• Any history of anaphylaxis in reaction to vaccination
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of serious psychiatric condition
• Poorly controlled asthma or thyroid disease
• Seizure in the past 3 years or treatment for seizure disorder in the past 3 years
• Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture
• Any other serious chronic illness requiring hospital specialist supervision
• Current anti-tuberculosis prophylaxis or therapy
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
• Suspected or known injecting drug abuse in the 5 years preceding enrolment
• Seropositive for hepatitis B surface antigen (HBsAg)
• Seropositive for hepatitis C virus (antibodies to HCV)
• Travel to a Ebola or Marburg endemic region during the study period or within the previous six months
• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis (see Appendix A and Appendix B)
• Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
• Inability of the study team to contact the volunteer's GP to confirm medical history and safety to participate

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Group 3b	cAd3-EBO Z at 5 x 10^10 vp	Single dose of cAd3-EBO Z at 5 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 1	cAd3-EBO Z at 1 x 10^10 vp	Single dose of cAd3-EBO Z at 1 x 10\^10 vp intramuscularly
Group 1b	cAd3-EBO Z at 1 x 10^10 vp	Single dose of cAd3-EBO Z at 1 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 1b	4.4x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 1 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 1c	cAd3-EBO Z at 1 x 10^10 vp	Single dose of cAd3-EBO Z at 1 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 1c	2.2x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 1 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 2b	4.4x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 2	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly
Group 2b	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 3	cAd3-EBO Z at 5 x 10^10 vp	Single dose of cAd3-EBO Z at 5 x 10\^10 vp intramuscularly
Group 2c	2.2x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 3c	2.2x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 5 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 4	2.2x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 2.2 x 10\^8 TCID50s MVA-BN® Filo at day 7
Group 6	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 4.4 x 10\^7 TCID50s MVA-BN® Filo at day 7
Group 2c	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 4	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 2.2 x 10\^8 TCID50s MVA-BN® Filo at day 7
Group 3b	4.4x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 5 x 10\^10 vp intramuscularly, followed by 4.4x10\^8 TCID50s MVA-BN® Filo
Group 7	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 4.4 x 10\^7 TCID50s MVA-BN® Filo at day 14
Group 7	4.4 x 10^7 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 4.4 x 10\^7 TCID50s MVA-BN® Filo at day 14
Group 5	2.2x10^8 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 2.2 x 10\^8 TCID50s MVA-BN® Filo at day 14
Group 3c	cAd3-EBO Z at 5 x 10^10 vp	Single dose of cAd3-EBO Z at 5 x 10\^10 vp intramuscularly, followed by 2.2x10\^8 TCID50s MVA-BN® Filo
Group 5	cAd3-EBO Z at 2.5 x 10^10 vp	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 2.2 x 10\^8 TCID50s MVA-BN® Filo at day 14
Group 6	4.4 x 10^7 TCID50s MVA-BN® Filo	Single dose of cAd3-EBO Z at 2.5 x 10\^10 vp intramuscularly at day 0, followed by 4.4 x 10\^7 TCID50s MVA-BN® Filo at day 7

Primary Outcome Measures

Name	Time	Method
Safety and tolerability of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses	6 months	The specific endpoints for safety and reactogenicity will be actively and passively collected data on adverse events.

Secondary Outcome Measures

Name	Time	Method
Cellular and humoral immunogenicity of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses	6 months	The primary immunogenicity outcome measures are ELISA and neutralization antigen-specific assays for antibody responses and intracellular cytokine staining (ICS) assay for T cell responses.

Trial Locations

Locations (1)

Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford; 🇬🇧 Oxford, Oxfordshire, United Kingdom