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

A Phase Ia, Dose-Escalating, Safety and Immunogenicity Trial of the Monovalent Zaire Ebola Viral Vector Candidate Vaccine cAd3-EBO Z and the Heterologous Prime-boost Candidate Vaccine Regimen cAd3-EBO Z and MVA-BN® Filo in Healthy UK Adults

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 91
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LE
      • Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly	Biological: cAd3-EBO Z at 1 x 10^10 vp; Low dose cAd3-EBO Z
Experimental: Group 1b; Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo	Biological: cAd3-EBO Z at 1 x 10^10 vp; Low dose cAd3-EBO Z; Biological: 4.4x10^8 TCID50s MVA-BN® Filo; High dose MVA-BN® Filo
Experimental: Group 1c; Single dose of cAd3-EBO Z at 1 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo	Biological: cAd3-EBO Z at 1 x 10^10 vp; Low dose cAd3-EBO Z; Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Low dose MVA-BN® Filo
Experimental: Group 2; Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly	Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z
Experimental: Group 2b; Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo	Biological: 4.4x10^8 TCID50s MVA-BN® Filo; High dose MVA-BN® Filo; Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z
Experimental: Group 2c; Single dose of cAd3-EBO Z at 2.5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo	Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Low dose MVA-BN® Filo; Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z
Experimental: Group 3; Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly	Biological: cAd3-EBO Z at 5 x 10^10 vp; High dose cAd3-EBO Z
Experimental: Group 3b; Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 4.4x10^8 TCID50s MVA-BN® Filo	Biological: 4.4x10^8 TCID50s MVA-BN® Filo; High dose MVA-BN® Filo; Biological: cAd3-EBO Z at 5 x 10^10 vp; High dose cAd3-EBO Z
Experimental: Group 3c; Single dose of cAd3-EBO Z at 5 x 10^10 vp intramuscularly, followed by 2.2x10^8 TCID50s MVA-BN® Filo	Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Low dose MVA-BN® Filo; Biological: cAd3-EBO Z at 5 x 10^10 vp; High dose cAd3-EBO Z
Experimental: Group 4; 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	Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Low dose MVA-BN® Filo; Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z
Experimental: Group 5; 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	Biological: 2.2x10^8 TCID50s MVA-BN® Filo; Low dose MVA-BN® Filo; Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z
Experimental: Group 6; 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	Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z; Biological: 4.4 x 10^7 TCID50s MVA-BN® Filo; Very low dose MVA-BN® Filo
Experimental: Group 7; 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	Biological: cAd3-EBO Z at 2.5 x 10^10 vp; Medium dose cAd3-EBO Z; Biological: 4.4 x 10^7 TCID50s MVA-BN® Filo; Very low dose MVA-BN® Filo

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cellular and humoral immunogenicity of the Ebola Zaire vaccine cAd3-EBO Z when administered to healthy volunteers at 3 doses	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.	6 months

Collaborators and Investigators

• Sponsor: University of Oxford
• Collaborators: National Institute of Allergy and Infectious Diseases (NIAID); Wellcome Trust
• Investigators: Principal Investigator: Adrian V Hill, University of Oxford

Publications and helpful links

General Publications

• Lambe T, Rampling T, Samuel D, Bowyer G, Ewer KJ, Venkatraman N, Edmans M, Dicks S, Hill AV, Tedder RS, Gilbert SC. Detection of Vaccine-Induced Antibodies to Ebola Virus in Oral Fluid. Open Forum Infect Dis. 2016 Feb 22;3(1):ofw031. doi: 10.1093/ofid/ofw031. eCollection 2016 Jan.
• Ewer K, Rampling T, Venkatraman N, Bowyer G, Wright D, Lambe T, Imoukhuede EB, Payne R, Fehling SK, Strecker T, Biedenkopf N, Krahling V, Tully CM, Edwards NJ, Bentley EM, Samuel D, Labbe G, Jin J, Gibani M, Minhinnick A, Wilkie M, Poulton I, Lella N, Roberts R, Hartnell F, Bliss C, Sierra-Davidson K, Powlson J, Berrie E, Tedder R, Roman F, De Ryck I, Nicosia A, Sullivan NJ, Stanley DA, Mbaya OT, Ledgerwood JE, Schwartz RM, Siani L, Colloca S, Folgori A, Di Marco S, Cortese R, Wright E, Becker S, Graham BS, Koup RA, Levine MM, Volkmann A, Chaplin P, Pollard AJ, Draper SJ, Ballou WR, Lawrie A, Gilbert SC, Hill AV. A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA. N Engl J Med. 2016 Apr 28;374(17):1635-46. doi: 10.1056/NEJMoa1411627. Epub 2015 Jan 28.

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2014
• Primary Completion (Actual): August 22, 2017
• Study Completion (Actual): August 22, 2017

Study Registration Dates

• First Submitted: September 10, 2014
• First Submitted That Met QC Criteria: September 15, 2014
• First Posted (Estimate): September 16, 2014

Study Record Updates

• Last Update Posted (Actual): July 6, 2018
• Last Update Submitted That Met QC Criteria: July 4, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Ebola; Zaire
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Mononegavirales Infections; Hemorrhagic Fevers, Viral; Filoviridae Infections; Hemorrhagic Fever, Ebola
• Other Study ID Numbers: EBL01; 2014-003518-10 (EudraCT Number)