Ad26.ZEBOV Booster in Children Previously Vaccinated With Ad26.ZEBOV and MVA-BN-Filo (EBOVAC Booster Study)
Condition: Ebola Virus Disease
MeSH terms: Virus Diseases; Hemorrhagic Fever, Ebola
Study type: Interventional
Phase: Phase 2

Summary: 
      This is an open-label study evaluating the safety and immunogenicity of a booster dose of
      Ad26.ZEBOV administered to children who were previously vaccinated with Ad26.ZEBOV followed
      by MVA-BN-Filo 56 days later.
    

Detailed description: 
      RATIONALE:

      Over 600 children have received the adenovirus serotype 26 expressing the Ebola virus Mayinga
      glycoprotein (Ad26.ZEBOV), modified Vaccinia Ankara Bavarian Nordic vector expressing
      multiple filovirus proteins (MVA- BN-Filo) Ebola vaccine regimen in the EBL2002 and EBL3001
      clinical trials. The vaccine regimen was well tolerated and highly immunogenic in children;
      however, the durability of vaccine-induced immune responses is not known. In adults
      previously vaccinated with the Ad26.ZEBOV and MVA-BN-Filo regimen, a booster vaccination with
      Ad26.ZEBOV was safe and induced a strong anamnestic response within seven days of the booster
      vaccination. It is important to establish if a booster dose of Ad26.ZEBOV is safe and
      immunogenic also in children, as this can guide the clinical use of the Ad26.ZEBOV,
      MVA-BN-Filo vaccine regimen in this age group. For example, it could support the strategy of
      boosting immunised children at the start of an Ebola outbreak.

      STUDY OBJECTIVES AND HYPOTHESIS:

      This study aims to evaluate the safety and immunogenicity of an Ad26.ZEBOV booster dose in
      healthy children who were previously (>2 years) vaccinated with the Ad26.ZEBOV (dose 1)
      followed by MVA-BN-Filo (dose 2) 56 days later, by monitoring adverse events (AEs) following
      the booster vaccination and by assessing binding antibody responses using the Filovirus
      Animal Non-Clinical Group (FANG) Enzyme-Linked Immunosorbent Assay (ELISA).

      Primary Objectives:

        -  To assess the safety and tolerability of a booster dose of Ad26.ZEBOV at a dose of
           5x10^10 viral particles (vp) in children previously vaccinated with the Ad26.ZEBOV,
           MVA-BN-Filo vaccine regimen with a 56-day interval. Safety and tolerability will be
           assessed by measuring:

             1. Incidence of solicited local (at the administration site) and systemic adverse
                events as assessed on the day of booster vaccination and by diary card for 7 days
                after booster vaccination.

             2. Incidence of unsolicited adverse events from the day of the booster vaccination to
                28 days post booster vaccination.

        -  To assess vaccine-induced humoral immune responses to the Ebola virus glycoprotein (EBOV
           GP), as measured by FANG ELISA (EU/ml), at 7 and 21 days following a booster dose of
           Ad26.ZEBOV at a dose of 5x10^10 vp in children previously vaccinated with the
           Ad26.ZEBOV, MVA-BN-Filo vaccine regimen with a 56-day interval.

      Exploratory Objectives

      • To assess neutralising antibody responses directed against the Ad26 vector before booster
      vaccination as measured by a virus neutralization assay (VNA).

      Hypothesis: as this study is designed to provide descriptive information regarding safety and
      immunogenicity without formal treatment comparisons, no formal statistical hypothesis testing
      is planned.

      OVERVIEW OF THE STUDY:

      This is an open-label study evaluating the immune response to a booster dose of Ad26.ZEBOV
      administered to children who were previously vaccinated with Ad26.ZEBOV followed by
      MVA-BN-Filo 56 days later. Only subjects who received the Ad26.ZEBOV and MVA-BN-Filo regimen
      during their participation in the VAC52150EBL3001 (EBOVAC-Salone) vaccine trial
      (ClinicalTrials.gov Identifier: NCT02509494), are eligible for enrolment in this study.
      Participants will be recruited in two age groups: children aged 4-11 years at the time of
      dose 1 vaccination and children aged 1-3 years at the time of dose 1 vaccination in the
      EBOVAC-Salone trial. Approximately 25 subjects will be enrolled in each of these two age
      groups. Parents/guardians will be asked to consent for the participation of their children in
      the study. Children aged 7 years and older at the time of enrolment in this study will be
      asked to give positive assent for their participation. Participants will be followed up to 28
      days after their booster vaccination. The study will be conducted in Kambia, Sierra Leone.

      Study Population: potential participants must be healthy children (based on physical
      examination, medical history, a haematological assessment and clinical judgment) who received
      the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in the EBOVAC-Salone trial and were aged ≥1 to
      ≤11 years at the time of dose 1 vaccination. They must also be enrolled in the long-term
      follow-up study to the EBOVAC-Salone trial, VAC52150EBL3005 (EBOVAC-Salone Extension study,
      ClinicalTrials.gov Identifier: NCT03820739) but not in the immunogenicity subset.

      Dosage and administration: a single dose of Ad26.ZEBOV at a dose of 5x10^10 vp administered
      intramuscularly.

      Safety evaluations: solicited local (at the administration site) and systemic AEs will be
      assessed on the day of vaccination and using a diary for a period of 7 days following the
      booster vaccination. Unsolicited AEs will be tracked for 28 days following booster
      vaccination, while serious adverse events will be tracked for the duration of the study.

      Immunogenicity evaluations: blood will be drawn for assessments of immune responses at 7 and
      21 days post booster vaccination.

      STATISTICAL METHODS:

      The primary analysis will be done when all subjects have completed their 28-day post-booster
      visit or discontinued earlier. This analysis will include all available data up to this
      point.

      Sample Size Determination: the sample size is a convenience sample and is not based on formal
      hypothesis testing considerations.

      Safety analysis: no formal statistical testing of safety data is planned. Safety data will be
      analysed descriptively by age group, 1-3 years and 4-11 years (age the participant was when
      they received dose 1 vaccination in the EBOVAC-Salone trial).

      Immunogenicity analysis: no formal hypothesis on immunogenicity will be tested. Descriptive
      statistics (i.e. geometric mean and 95% confidence interval, as appropriate) will be
      calculated for continuous immunologic parameters at all available time points. Graphical
      representations of immunologic parameters will be made as applicable.

      Frequency tabulations will be calculated for discrete (qualitative) immunologic parameters
      (i.e. responder rate), as applicable. Responders rate defined as >2.5-time increase over
      baseline value (or lower limit of quantitation [LLOQ]) pre-dose 1 vaccination in the
      EBOVAC-Salone trial, will be calculated depending on availability of sample results from the
      EBOVAC-Salone trial.
    

Intervention name(s): Ad26.ZEBOV booster vaccination, given at a dose of 5x10^10 vp, via IM injection
Intervention type(s): Drug
Intervention description(s): Ad26.ZEBOV is a monovalent, replication-incompetent adenovirus serotype 26-based vector that expresses the full-length Ebola virus Mayinga glycoprotein
Intervention model: Single Group Assignment
Intervention model description: All participants will receive a single dose of Ad26.ZEBOV at a dose of 5x10^10 viral particles (vp) administered intramuscularly.
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ad26.ZEBOV; booster vaccination; children