Evaluation of a New Ebola Vaccine Using a Short-interval Prime-boost Vaccination
Condition: Ebola Virus Disease
MeSH terms: Virus Diseases; Hemorrhagic Fever, Ebola
Study type: Interventional
Phase: Phase 1

Summary: 
      This is a clinical trial in which healthy volunteers will be administered two experimental
      Ebola vaccines: ChAd3-EBO Z and MVA-EBO Z. Two groups of volunteers will be vaccinated with
      both vaccines one after the other in a prime/boost regimen.

      All ChAd3-EBO Z doses are 2.5 x 10^10 - 3.7 x 10^10 vp and all MVA-EBO Z doses are 1.0 x 10^8
      pfu.

      All volunteers will receive a ChAd3-EBO Z priming vaccine and a MVA-EBO Z boosting vaccine 7
      days later.

      The site of administration of the MVA-EBO Z vaccine differs between the two groups:

      Group 1 will receive the MVA-EBO Z vaccine in the same arm as the ChAd3-EBO Z vaccine.

      Group 2 will receive the MVA-EBO Z vaccine in the opposite arm from the ChAd3-EBO Z vaccine.

      The study will assess the safety of the vaccinations, and the immune responses to
      vaccination. Immune responses are measured by tests on blood samples.

      The ChAd3-EBO Z and MVA-EBO Z vaccines are called viral vectored vaccines. They are made from
      viruses which are modified so that they cannot multiply. The viruses have extra DNA in them
      so that after injection, the body makes Ebola proteins (but Ebola does not develop), so that
      the immune system builds a response to Ebola without having been infected by it.

      Healthy volunteers will be recruited in Dakar, Senegal. The study will be funded by GSK.
    

Detailed description: 
      The CHUD study team will hold sensitisation meetings, in specific areas targeting specific
      populations, to explain the study to potential volunteers. During these meetings the
      investigators will explain the following: the need for a vaccine (including a simple picture
      of the burden of the Ebola disease and how it affects the community); the current status of
      vaccine development (including the fact that this is likely to be a prolonged process that
      probably will not influence the course of the current epidemic); the study screening and
      informed consent procedure; risks of vaccination and the unproven benefits of this
      vaccination. It will be stressed that this is an experimental vaccine and there is no current
      evidence that it will provide protection, and that it will therefore still be necessary to
      take preventive measures and to seek treatment if ill for any reason after vaccination.

      After these sensitisation meetings, the CT team will actively identify. The study will be
      further explained to eligible participants on individual basis. Potential volunteers will be
      invited to the CHUD CT site for further discussion. Potential volunteers will be informed
      that they are free to withdraw from the CT at any time without giving any reason. Individuals
      who feel that the trial is appropriate for them will be invited to attend a formal screening
      visit.

      Detailed information about the study will be provided in a Participant Information Sheet
      (PIS) at least 24 hours prior to the consent being undertaken. The informed consent process
      will start before the screening visit. The volunteer will be given the opportunity to ask
      about details of the trial, and will then have time to consider whether or not to
      participate. The investigators will ensure that the volunteers are briefed on the contents of
      the PIS in the language they understand. The investigators will also ensure that all
      volunteers fully understand the risks. Any volunteer who appears to have less than complete
      understanding will not be enrolled.

      All volunteers will sign and date the informed consent form before any study specific
      procedures (including screening visit) are performed. If the volunteer is illiterate, s/he
      will sign the informed consent form; in the latter case a literate adult impartial witness
      will be present throughout the whole consenting process, write subject's name and date of
      signature and will sign and date the consent form. Volunteers will sign and date two copies
      of the consent form, one for them to take away and keep, and one to be stored in the
      subject's medical records.

      Vaccinations in Group 1 can commence 7 days after vaccination after interim safety review of
      the first 5 volunteers receiving the same dose in the UK CT. The first 5 volunteers will be
      vaccinated in a staggered fashion.

      The first volunteer to receive the ChAd63-EBO Z vaccine dose in Group 1 will be vaccinated
      alone and we will wait 24 hours before vaccinating subsequent volunteers in this group. Two
      further Group 1 volunteers will be vaccinated 24 hours after the first, and then at least
      another 24 hours gap will pass before vaccinating further subjects receiving the ChAd63-EBO Z
      vaccine in Groups 1 & 2.

      The same staggered vaccine administration procedure will be adopted for vaccinations with the
      MVA-EBO Z vaccine. A total of 20 volunteers will be enrolled in this group.

      In Group 2, vaccination can commence after 5 volunteers in Groups 1 have received the
      ChAd63-EBO Z vaccine dose. The same staggered vaccine administration procedure as for Group 1
      will be adopted for vaccinations with the MVA-EBO Z vaccine. A total of 20 volunteers will be
      enrolled in this group.

      Volunteers will be visited daily at home by a study field worker or nurse to record adverse
      events (solicited and unsolicited for six consecutive days after vaccination). Additional
      scheduled visits at the CHUD clinic will be at day 7, 14, 28, 35, 56, 90, 180 post-first
      vaccination during which interim history will be collected, physical examination and blood
      tests performed at the time-points indicated in the schedule of attendances. Blood will also
      be taken for exploratory immunology analysis.

      All volunteers will be followed up for 6 months beginning from the day of the first
      vaccination.
    

Intervention name(s): ChAd3-EBO Z; MVA-EBO Z
Intervention type(s): Biological; Biological
Intervention description(s): This is a viral vectored vaccine using a chimpanzee adenovirus as a vector encoding a Zaire strain Ebola glycoprotein; This is a viral vectored vaccine using a modified vaccinia Ankara virus as a vector encoding a Zaire strain Ebola virus glycoprotein
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ebola; vaccine; safety; immunogenicity