Clinical Trial Results:
Evaluating the Long Term Immunogenicity of adenoviral and MVA vectored Ebola vaccine schedules and response to late boosting with AD26.ZEBOV vaccine: an open-label clinical trial
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Summary
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EudraCT number |
2017-004610-26 |
Trial protocol |
GB |
Global end of trial date |
09 Mar 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
06 Jul 2022
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First version publication date |
06 Jul 2022
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Other versions |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
OVG2017/10
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Additional study identifiers
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ISRCTN number |
ISRCTN10481319 | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
University of Oxford, Clinical Trials and Research Governance (CTRG)
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Sponsor organisation address |
Boundary Brook House, Oxford, United Kingdom, OX3 7GB
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Public contact |
Matthew Snape, University of Oxford, 44 1865611400, matthew.snape@paediatrics.ox.ac.uk
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Scientific contact |
Matthew Snape, University of Oxford, 44 1865611400, matthew.snape@paediatrics.ox.ac.uk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
20 Jun 2022
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Is this the analysis of the primary completion data? |
No
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Global end of trial reached? |
Yes
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Global end of trial date |
09 Mar 2021
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
To evaluate the long-term persistence of immunity (both cellular immunity and antibody levels) in healthy volunteers who were vaccinated approximately 2-5 years previously with investigational Ebola vaccines (ChAd3-EBO Z, MVA–BN-FILO, MVA-EBO-Z and Ad26.ZEBOV), and to assess the response to a booster dose of an investigational Ebola vaccine (Ad26.ZEBOV) given approximately 2-5 years after the initial vaccines.
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Protection of trial subjects |
The trial complied with the General Data Protection Regulations and the Data Protection Act.
Participants were enrolled with fully informed consent, including the safety data known about the vaccines up to that point, i.e. mild vaccine reactions are common and include local reactions such as pain, tenderness and swelling at the injection site and systemic reactions such as mild fever, fatigue and headache. Fever is the most commonly reported systemic reaction with an incidence of up to 10%. There is a small risk of pain and bruising as a result of blood sampling. Very occasionally, participants may feel faint or experience a vaso-vagal episode as a result of taking blood.
Possible side effects were explained to the participants and they were told they can take painkillers/ antipyretics (e.g. paracetamol). Participants were observed for 30 minutes after receiving the vaccine in case of any immediate reactions. They were also given a phone number for 24 hour contact with a study doctor if they were concerned about vaccine reactions and asked to keep a diary card reporting solicited reactions, and to report any serious adverse events. The possible adverse effects of blood sampling were minimised by ensuring that the participant was aware of when and how the blood was taken and provided an opportunity to ask questions about the procedure. Blood was taken by a doctor or nurse experienced and trained in taking blood and in managing any adverse events associated with the procedure. Participants were compensated for the inconvenience of having blood taken.
As with any vaccine there was the rare risk of an anaphylactic reactions to these Ebola vaccines and study staff were trained to manage this. The investigational nature of Ad26.ZEBOV with the potential for unknown side effects, was made clear to participants as part of the informed consent process, however adenoviral based vaccines have been given to thousands of participants without significant safety concerns.
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Background therapy |
The study population consisted of participants who had received immunisation with Ebola vaccines (ChAd3-EBO-Z, MVA-BN-FILO, MVA-EBO-Z or AD26.ZEBOV) in previous Ebola vaccine studies EBL01, EBL04 and EBL05. | ||
Evidence for comparator |
The aim of the study was to assess the impact on the duration of the immune response of giving a booster dose of an Ebola vaccine (AD26.ZEBOV), 2-5 years after the initial immunisation regimens. The duration of a persistent immunological response from Ebola vaccine would determine whether additional booster dosage would be required to maintain a protective level of immunity in such a cohort. The sustainability of an immune response would also indicate how many such boosters would be required and at what intervals. All such information would be crucial in determining the Ebola vaccination policy by WHO and countries in the Ebola endemic zone. | ||
Actual start date of recruitment |
30 Apr 2019
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
United Kingdom: 48
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Worldwide total number of subjects |
48
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EEA total number of subjects |
0
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
48
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
The study population consisted of participants who had received immunisation with Ebola vaccines (ChAd3-EBO-Z, MVA-BN-FILO, MVA-EBO-Z or AD26.ZEBOV) in previous Ebola vaccine studies EBL01, EBL04 and EBL05. Recruitment period: September - December 2019; territories - United Kingdom. | |||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
Baseline assessments and information collection was carried out by trained study team member. Participants were to have received at least one vaccine during Ebola vaccine studies. Exclusion criteria was previous malignancy, pregnancy, breast feeding, new significant medical or surgical history, receipt of other adeno virus vaccine. | |||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||||||||||||||||||||
Allocation method |
Non-randomised - controlled
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Blinding used |
Not blinded | |||||||||||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Ebola vaccine AD26.ZEBOV boosted group | |||||||||||||||||||||||||||
Arm description |
Investigational medicinal product, Ebola vaccine AD26.ZEBOV, was administered as a booster vaccine following previous participation in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV. | |||||||||||||||||||||||||||
Arm type |
Active comparator | |||||||||||||||||||||||||||
Investigational medicinal product name |
AD26.ZEBOV
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Investigational medicinal product code |
AS1
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Other name |
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Pharmaceutical forms |
Solution for injection, Solution for injection in multidose container
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Routes of administration |
Injection , Intramuscular use
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Dosage and administration details |
The vaccine dosage was a 0.5 ml dose of AD26.ZEBOV, containing 5 x 10^10 vp. The vaccine was administered as an IM injection in either deltoid. The dosage and route of administration have been shown to be immunogenic in Phase l and ll studies of the IMP, with an acceptable safety profile. The vaccine was administered as a single dose (booster).
AD26.ZEBOV is a monovalent, recombinant, replication incompetent AD26-based vaccine expressing the full length Ebola virus (EBOV, formerly known as Zaire ebolavirus) Mayinga glycoprotein (GP), produced in the human cell line PER.C6®. It was supplied in a single use 2mL glass vial with an extractable volume of 0.5mL at a concentration of 1×10^11 virus particles (vp)/mL. The vaccine was formulated in final formulation buffer.
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Arm title
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Non-boosted group | |||||||||||||||||||||||||||
Arm description |
Previous participants in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV who wished to participate in the study but did not wish to receive a booster vaccine. | |||||||||||||||||||||||||||
Arm type |
No intervention | |||||||||||||||||||||||||||
Investigational medicinal product name |
No investigational medicinal product assigned in this arm
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Baseline characteristics reporting groups
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Reporting group title |
Ebola vaccine AD26.ZEBOV boosted group
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Reporting group description |
Investigational medicinal product, Ebola vaccine AD26.ZEBOV, was administered as a booster vaccine following previous participation in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Non-boosted group
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Reporting group description |
Previous participants in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV who wished to participate in the study but did not wish to receive a booster vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Ebola vaccine AD26.ZEBOV boosted group
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Reporting group description |
Investigational medicinal product, Ebola vaccine AD26.ZEBOV, was administered as a booster vaccine following previous participation in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV. | ||
Reporting group title |
Non-boosted group
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Reporting group description |
Previous participants in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV who wished to participate in the study but did not wish to receive a booster vaccine. | ||
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End point title |
Humoral immunity: Ebola GP specific IgG (GM) [1] | ||||||||||||||||||
End point description |
Ebola specific (Anti-Zaire) GP IgG as measured by ELISA - presented as Geometric Mean (95% CI)
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End point type |
Primary
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End point timeframe |
First visit (V1, day 0) and 12 months from V1 (day 365)
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| Notes [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistical analysis - reported as Geometric Mean (95% CI). |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Cellular immunity: Ebola GP specific T cell cytokine response [2] | ||||||||||||||||||
End point description |
Ebola GP specific T cell cytokine response measured using ex vivo interferon-γ enzyme-linked immunosorbent spot (ELISPOT)
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End point type |
Primary
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End point timeframe |
First visit (V1, day 0) and 12 months from V1 (day 365)
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| Notes [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistical analysis - reported as Median (IQR). |
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| No statistical analyses for this end point | |||||||||||||||||||
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End point title |
Humoral immunity: Ebola GP specific IgG (titre ≥ 166 EU) [3] | ||||||||||||||||||
End point description |
Ebola specific (Anti-Zaire) GP IgG as measured by ELISA - presented as percentage participants with IgG titre ≥ 166 EU
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End point type |
Primary
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End point timeframe |
First visit (V1, day 0) and 12 months from V1 (day 365)
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| Notes [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point. Justification: Descriptive statistical analysis - reported as percentage participants with IgG titre ≥ 166 EU. |
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| No statistical analyses for this end point | |||||||||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Days 0-3 post immunisation
Days 0-28 post immunisation
Days 0-365 post immunisation
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Adverse event reporting additional description |
Solicited adverse events within first 3 days after immunisation 0 - eDiary
Unsolicited medically attended adverse events within first month after immunisation - eDiary, vital signs at D0, D7, D28
Serious adverse events experienced by any participant throughout study
Solicited non-SAEs are not reported here but will be reported in a publication.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
Protocol | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
v5.1
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Reporting groups
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Reporting group title |
Ebola vaccine AD26.ZEBOV boosted group
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Reporting group description |
Investigational medicinal product, Ebola vaccine AD26.ZEBOV, was administered as a booster vaccine following previous participation in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Non-boosted group
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Reporting group description |
Previous participants in studies of regimens of Ebola vaccines ChAd3-EBO-Z, MVA-EBO-Z, MVA–BN-FILO and AD26.ZEBOV who wished to participate in the study but did not wish to receive a booster vaccine. | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? Yes | |||
Date |
Amendment |
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10 Jan 2019 |
- Addition of a PI signature page.
- Update to planned trial dates.
- Clarification and strengthening of safety reporting wording in section 10. |
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01 Apr 2019 |
- Update to full study title to aid clarity
- Update to objectives to be inclusive of all participants who received completed immunisation regimens in EBL01, EBL04 and EBL05
- Addition of Visit 2, 7 days post immunisation for booster only group in order to study the early response to immunisation
- Update to risk safety language and clarification on safety reporting and vaccine storage, which have come about following discussions with the vaccine supplier Janssen
- Update to text relating to intellectual property as these details were to be covered in the Agreement with Janssen
- Update to number of participants who received AD26.ZEBOV (as opposed to placebo) in previous studies in line with the updated IB
- Correction of information relating to asking GPs to inform OVG of any reason a participant should not take part in the study
- Correction of summary study design |
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10 Dec 2019 |
- Change of PI at the NIHR/Wellcome Trust Imperial Clinical Research Facility Hammersmith Hospital Site |
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Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| Results will be published later in 2022 and distributed to participants. The publication will contain the data for the secondary objectives and solicited non-SAE, which are not reported here. | |||
