An Open Label Study to Evaluate the Safety and Immunogenicity of an Ad26.ZEBOV Booster Dose in Children Previously Vaccinated With the Ad26.ZEBOV and MVA-BN-Filo Vaccine Regimen
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 50
- Locations
- 1
- Primary Endpoint
- Number of Participants With Solicited Systemic Adverse Events
Study Overview
Brief 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:
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 3 Years to 16 Years (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Child must be enrolled in the VAC52150EBL3005 (EBOVAC-Salone Extension) study but not in the immunogenicity subset of EBOVAC-Salone Extension study.
- •Child must be a former participant in the VAC52150EBL3001 (EBOVAC-Salone) trial, and have received Ad26.ZEBOV (dose 1) vaccination followed by the MVA-BN-Filo (dose 2) vaccination within the EBOVAC- Salone trial window for dose 2 vaccination.
- •Child must have been aged 1 to 11 years old at the time of dose 1 vaccination in the EBOVAC-Salone trial.
- •The parent/guardian must consent for their child to participate in the VAC52150EBL2011 study. Children aged 7 years and older will be asked to give positive assent for their participation in the study.
- •The parent/guardian is willing/able to ensure that their child adheres to the prohibitions and restrictions specified in this protocol.
- •Child must be healthy in the investigator's clinical judgement (and the parent/guardian's judgement) on the basis of medical history, physical examination, vital signs, and a haematological assessment (i.e. full blood count) performed at screening. Subjects must meet the following haematology parameters within 28 days before Day 1:
- •Haemoglobin ≥8.0 g/dL for children aged 1 to <5 years, ≥9g/dL for children aged 5 or older
- •Platelet count ≥100 x 10^9/L
- •White blood cell count ≥5.0 x 10^9/L
- •Adolescent girls who have started their menstrual periods and/or are ≥12 years of age at the time of screening, must have a negative urine β-hCG pregnancy test at screening and immediately prior to the booster vaccination on Day
- •The parent/guardian is available and willing to have their infant participate for the duration of the study visits.
- •The parent/guardian must have a means to be contacted.
- •The parent/guardian must pass the Test of Understanding (TOU)
Exclusion Criteria
- •Participants in the EBOVAC-Salone trial who were allocated to the control arm receiving the WHO- prequalified Meningococcal Group A, C, W135 and Y conjugate vaccine.
- •Participants in the EBOVAC-Salone trial who were age 12 years and older at the time of dose 1 vaccination.
- •Known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccine, e.g., polysorbate 80, ethylenediaminetetraacetic acid or L-histidine for Ad26.ZEBOV vaccine), including known allergy to chicken or egg proteins and aminoglycosides (gentamicin).
- •Presence of acute illness (this does not include minor illnesses such as mild diarrhoea or mild upper respiratory tract infection) or axillary temperature ≥38C on Day
- •Participants with such symptoms will be excluded from enrolment at that time but may be rescheduled for enrolment at a later date within the screening window.
- •Clinically significant history of skin disorder (e.g., psoriasis, contact dermatitis), allergy, symptomatic immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness as judged by the investigator or other delegated individual.
- •Adolescent girls who are known to be pregnant or breastfeeding at screening.
- •Received a blood transfusion or other blood products within 8 weeks of vaccination day.
- •Children who have been vaccinated with live-attenuated vaccines within 30 days before the study vaccination, and with inactivated vaccine within 15 days before the study vaccination.
- •Children who, in the opinion of the investigator, are unlikely to adhere to the requirements of the study or are unlikely to complete the vaccination and observation.
- •Any other finding which in the opinion of the investigator or other delegated individual would increase the risk of an adverse outcome from participation in the study.
Arms & Interventions
Study Intervention
All study participants will receive an Ad26.ZEBOV vaccine at a dose of 5x10^10 vp given via IM injection
Intervention: Ad26.ZEBOV booster vaccination, given at a dose of 5x10^10 vp, via IM injection (Drug)
Outcomes
Primary Outcomes
Number of Participants With Solicited Systemic Adverse Events
Time Frame: From the booster vaccination to 7 days post booster
Number and percentage of participants with at least one solicited systemic adverse event (i.e. arthralgia, chills, fatigue, headache, myalgia, nausea and pyrexia)
Number of Participants With Unsolicited Adverse Events
Time Frame: From the booster vaccination to 28 days post booster
Number and percentage of participants with at least one unsolicited adverse event
Pre-booster Baseline Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP)
Time Frame: day 1 before booster administration
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
Number of Participants With Solicited Local (at the Administration Site) Adverse Events
Time Frame: From the booster vaccination to 7 days post booster
Number and percentage of participants with at least one solicited local adverse event (i.e. pain, erythema, pruritus and swelling)
Number of Participants With Serious Adverse Events
Time Frame: From the booster vaccination to 28 days post booster
Number and percentage of participants with serious adverse events
Vaccine-induced Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP)
Time Frame: At 21 days post booster
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
Secondary Outcomes
No secondary outcomes reported