Evaluation of a New Ebola Vaccine Using a Short-interval Prime-boost Vaccination

A Phase Ib Safety and Immunogenicity Clinical Trial of Heterologous Prime-boost Immunisation With ChAd3-EBO Z and MVA-EBO Z in Healthy Senegalese Adult Volunteers Aged 18-50 Years.

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.

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.

Inclusion Criteria:

• Healthy adults aged 18 to 50 years
• Able and willing (in the Investigator's opinion) to comply with all study requirements
• For females only, willingness to practice continuous effective contraception (see section 6.4.3) during the study and a negative pregnancy test on the day(s) of screening and vaccination
• Agreement to refrain from blood donation during the course of the study
• Provide written informed consent

Exclusion Criteria:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned participation during the study period
• Prior receipt of an investigational Ebola or Marburg vaccine, a chimpanzee adenovirus vectored vaccine, an MVA vaccine or any other investigational vaccine likely to impact on interpretation of the trial data
• Receipt of any live, attenuated vaccine within 28 days prior to enrolment
• Receipt of any subunit or killed vaccine within 14 days prior to enrolment
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
• Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
• History of allergic disease or reactions likely to be exacerbated by any component of the vaccine, (e.g. egg products) including urticaria, respiratory difficulty or abdominal pain
• Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
• Any history of anaphylaxis in reaction to vaccination
• Pregnancy, lactation or willingness/intention to become pregnant during the study
• History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
• History of current or previous psychiatric illness.
• Poorly controlled asthma or thyroid disease
• Seizure in the past 3 years or treatment for seizure disorder in the past 3 years
• Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
• Any other serious chronic illness
• Current anti-tuberculosis prophylaxis or therapy
• Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
• Suspected or known injecting drug abuse in the 5 years preceding enrolment
• Seropositive for hepatitis B surface antigen (HBsAg)
• History of contact with suspected, probable or confirmed cases of Ebola in the previous 21 days
• Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis (see Appendix A & B)
• Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data