A Phase 2 interventional study of Ad26.ZEBOV booster vaccination, given at a dose of 5x10^10 vp, via IM injection in Ebola Virus Disease, sponsored by London School of Hygiene and Tropical Medicine. Completed at 1 site in Sierra Leone. Open to participants aged 3 Years to 16 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2023-12-13.
Sponsored by London School of Hygiene and Tropical Medicine · Phase 2, Interventional, and Prevention
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.
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:
Exploratory Objectives
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.
104 studies on the registry are indexed under Hemorrhagic Fever, Ebola; 13 are open to participants now.
This study's enrollment of 50 is below the median of 94 across 81 interventional studies indexed under Hemorrhagic Fever, Ebola.
Browse Hemorrhagic Fever, Ebola studies →London School of Hygiene and Tropical Medicine is the lead sponsor of 298 studies on the registry; 15 are open to participants now.
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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:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Live vaccines
Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
All study participants will receive an Ad26.ZEBOV vaccine at a dose of 5x10\^10 vp given via IM injection
Drug: Ad26.ZEBOV booster vaccination, given at a dose of 5x10^10 vp, via IM injection
Ad26.ZEBOV is a monovalent, replication-incompetent adenovirus serotype 26-based vector that expresses the full-length Ebola virus Mayinga glycoprotein
Number of Participants With Solicited Local (at the Administration Site) Adverse Events
Number and percentage of participants with at least one solicited local adverse event (i.e. pain, erythema, pruritus and swelling)
Time frame: From the booster vaccination to 7 days post booster
Number of Participants With Solicited Systemic Adverse Events
Number and percentage of participants with at least one solicited systemic adverse event (i.e. arthralgia, chills, fatigue, headache, myalgia, nausea and pyrexia)
Time frame: From the booster vaccination to 7 days post booster
Number of Participants With Unsolicited Adverse Events
Number and percentage of participants with at least one unsolicited adverse event
Time frame: From the booster vaccination to 28 days post booster
Number of Participants With Serious Adverse Events
Number and percentage of participants with serious adverse events
Time frame: From the booster vaccination to 28 days post booster
Pre-booster Baseline Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP)
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
Time frame: day 1 before booster administration
Vaccine-induced Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP)
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
Time frame: At 7 days post booster
Vaccine-induced Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP)
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
Time frame: At 21 days post booster
Participants were screened between 8 July and 18 August 2021 at one clinic in Kambia Town, located in Kambia District in the North West Province of Sierra Leone.
| Milestone | Study Intervention |
|---|---|
| Started | 50 |
| Completed | 50 |
| Not completed | 0 |
Number and percentage of participants with at least one solicited local adverse event (i.e. pain, erythema, pruritus and swelling)
| Participants | Study Intervention |
|---|---|
| Number of Participants With Solicited Local (at the Administration Site) Adverse Events | 18 |
Number and percentage of participants with at least one solicited systemic adverse event (i.e. arthralgia, chills, fatigue, headache, myalgia, nausea and pyrexia)
| Participants | Study Intervention |
|---|---|
| Number of Participants With Solicited Systemic Adverse Events | 16 |
Number and percentage of participants with at least one unsolicited adverse event
| Participants | Study Intervention |
|---|---|
| Number of Participants With Unsolicited Adverse Events | 32 |
Number and percentage of participants with serious adverse events
| Participants | Study Intervention |
|---|---|
| Number of Participants With Serious Adverse Events | 0 |
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
| ELISA units/mL | Study Intervention |
|---|---|
| Pre-booster Baseline Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP) | 640 (461 to 888) |
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
| ELISA units/mL | Study Intervention |
|---|---|
| Vaccine-induced Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP) | 28561 (20255 to 40272) |
EBOV GP antibody geometric mean concentration measured by FANG ELISA in Elisa Units (EU) per millilitre
| ELISA units/mL | Study Intervention |
|---|---|
| Vaccine-induced Humoral Immune Responses to the Ebola Virus Glycoprotein (EBOV GP) | 64690 (48356 to 86541) |
Collected over Solicited local and systemic adverse events were recorded from the booster vaccination (day 1) to 7 days after the booster vaccination (day 8) Unsolicited adverse events were recorded from the booster vaccination (day 1) to 28 days after the booster vaccination (day 29). Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Study Intervention | 0/50 (0%) | 0/50 (0%) | 32/50 (64%) |
| Event | Study Intervention |
|---|---|
| MalariaInfections and infestations | 25/50 |
| PainSkin and subcutaneous tissue disorders | 18/50 |
| HeadacheGeneral disorders | 11/50 |
| FatigueGeneral disorders | 8/50 |
| Upper respiratory tract infectionsInfections and infestations | 7/50 |
| ChillsGeneral disorders | 6/50 |
| PyrexiaGeneral disorders | 6/50 |
| Lower respiratory tract infection/pneumoniaInfections and infestations | 4/50 |
| NauseaGastrointestinal disorders | 3/50 |
| Worm infestationInfections and infestations | 2/50 |
| Age, Categorical(Participants) | Study Intervention |
|---|---|
| <=18 years | 50 |
| Between 18 and 65 years | 0 |
| >=65 years | 0 |
| Age, Continuous(years) | Study Intervention |
|---|---|
| Median | 6 (4 to 13) |
| Sex: Female, Male(Participants) | Study Intervention |
|---|---|
| Female | 19 |
| Male | 31 |
| Ethnicity (NIH/OMB)(Participants) | Study Intervention |
|---|---|
| Hispanic or Latino | 0 |
| Not Hispanic or Latino | 50 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Study Intervention |
|---|---|
| Sierra Leone | 50 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — The clinical trial results will be published in an open access, peer-reviewed journal, which will include the study protocol. A summary of the study results will be included within the trial registration record in PACTR and ClinicalTrials.gov Following publication of the primary and exploratory objectives as detailed in the protocol, individual de-identified participants' data and a data dictionary will be made available upon request via the London School of Hygiene \& Tropical Medicine research data repository, LSHTM Data Compass at http://datacompass.lshtm.ac.uk. Requests with a defined analysis plan can be sent via LSHTM Data Compass.
Supporting information: Study protocol
Time frame: within 12 months of the study completion date
Access criteria: open
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