This study is an open-label, monocentric (in Tshuapa province, DRC), phase 2 study to evaluate the immunogenicity and safety of Ad26.ZEBOV (5x1010 viral particles \[vp\]) as first dose and MVA-BN-Filo (1x108 50% infectious units \[Inf U\]) as second dose vaccination at a 56-day interval in health care providers (HCP) who may be exposed to Ebola in the event of a future Ebola outbreak in DRC. Additionally, after randomization (1:1) a booster of Ad26.ZEBOV (5x1010 vp) will be offered at respectively 1 year or 2 years after the first dose.
A planned total number of approximately 700 participants will be recruited from the Tshuapa province in DRC. At Day 1, interested participants will be assessed for their understanding of the study, will provide consent, their general health will be evaluated by the investigator, medical history (including vaccination history) will be collected, urine pregnancy testing for women of childbearing potential will be performed. Further during this first visit, vital signs will be measured and a blood sample for baseline immunogenicity assessment will be taken for testing of binding antibody level against EBOV GP using FANG ELISA, presence of pre-existing Human anti-EBOV GP IgG and anti-EBOV NP IgG using ELISA and on the first 100 subjects additionally testing for neutralizing antibody level against Ad26 and MVA vectors using respectively Ad26 VNA and MVA PRNT. Subsequently, a blood sample for baseline safety assessment will be performed to test hemoglobin, hematocrit, blood cell count (red and white), platelet count, urea, creatinine and transaminases. After these primary assessments, they will be vaccinated with first dose Ad26.ZEBOV vaccine. They will be given instructions to contact the study team for any serious adverse event that occurs up until 6 months after each vaccination, or in case of pregnancy of the participant during the study. Lastly on day 1, randomization will be performed (1:1) to determine timing of the booster vaccine at 1 year or 2 years after first dose. Contact information will be verified and an appointment for the second dose on Day 57 will be arranged.
At Day 57, participants will return to the study site for urine pregnancy testing for women of childbearing potential, vital signs measurement, assessment of safety (serious adverse events), for a blood sample for immunogenicity assessment (the binding antibody levels against EBOV GP using FANG ELISA) and afterwards administration of the MVA-BN-Filo vaccination, and they will be reminded to contact the study team for any serious adverse event that occurs, or in case of pregnancy of the participant during the study. Contact information will be verified and an appointment for the 21-day post-dose 2 (Day 78) visit will be arranged.
At 21 days post-dose 2 (Day 78), all participants will return to the study site for assessment of safety (serious adverse events) and collection of a blood sample for immunogenicity assessment. Contact information will be re-verified. They will be reminded to contact the study team for any serious adverse event that occurs, or in case of pregnancy of participant.
At approximately 6 months post-dose 2 vaccination, participants will be contacted by phone to inquire about any occurrence of serious adverse events, and to confirm contact information for additional follow up at 1 year post-first dose vaccination. At 1 year after first vaccine dose, a blood sample will be collected for immunogenicity assessment of all participants (where applicable, pre-administration of the booster dose).
Depending on randomization performed at Day 1, the booster vaccination with Ad26.ZEBOV (5x1010 vp) will be given at 1 year after the first dose or 2 years post-first dose. Participants will be asked to collect solicited adverse events in a participant diary starting on the day of vaccination and continuing for the subsequent 7 days. At day 8 post booster (PB) the safety data including solicited adverse events will be reviewed and a blood sample for immunogenicity will be taken to document the immunity response. At 6 months PB, the participants will be contacted by phone and questioned about any serious adverse events that have occurred since the last vaccination. For all participants at 2 years after first dose, a sample will be collected for immunogenicity assessment (where applicable, pre-administration of the booster dose).
The total duration of the study is 2 years and 6 months post-first dose.
