safety, tolerability and immunogenicity study of 2-dose heterologous regimens for ebola vaccines ad26.zebov/mva-bn-filo

Conditions: Hemorrhagic Fever, Ebola

Summary: the purpose of this study is to assess the safety, tolerability and immunogenicity of different vaccination schedules of ad26.zebov and mva-bn-filo administered intramuscularly (im) as 2-dose heterologous regimens in healthy and in hiv-infected adults.

this is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, 2-part, phase 2 study of ad26.zebov and mva-bn-filo in healthy and hiv infected adults. in part 1, dose 1 vaccination with mva-bn-filo will be followed by dose 2 vaccination with ad26 14 days later in the us. in part 2, two regimens will be investigated. the first regimen will be ad26 dose 1 vaccination followed by mva-bn-filo dose 2, 28 days later and the second regimen will be mva-bn-filo dose 1 vaccination followed by ad26.zebov dose 2, 14 days later in africa. the study consists of a screening phase of up to 8 weeks (starting from the moment the participants signs the icf), a vaccination phase, in which participants will be vaccinated at baseline (day 1) followed by a dose 2 vaccination on day 15 or 29, and a post-dose 2 follow-up phase of maximum 1 year post-dose 2 vaccination. upon completion of 6-month post dose 2 visit those participants who received active vaccine will enter long-term follow-up until the 1 year post dose 2 vaccination visit to assess long-term safety and immunogenicity.

Eligibility criteria:
inclusion criteria: * participant must be healthy in the investigator's clinical judgment on the basis of medical history, physical examination and vital signs performed at screening * participant must be healthy on the basis of clinical laboratory tests and electrocardiogram (ecg) (only in participants \>50 years) performed at screening. if the results of the laboratory screening tests and ecg are outside the institutional normal reference ranges, the participant may be included only if the investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study * a woman of childbearing potential must have a negative urine β-human chorionic gonadotropin \[beta-hcg\] pregnancy test at screening and a negative urine \[beta-hcg\] pregnancy test immediately prior to each study vaccine administration * a man who is sexually active with a woman of childbearing potential must be willing to use condoms for sexual intercourse beginning prior to dose 1 vaccination until at least 3 months after the dose 2 vaccination, unless a vasectomy was performed more than 1 year prior to screening * participant must pass the test of understanding (tou) * additional inclusion criteria for hiv-infected participants a) participants must have a positive hiv-1 and/or -2 serology test within 6 months of screening, including the day of screening; b) participants must have a screening cd4+ cell count \>200 cells/microliter (mcl); c) in part 1, all participants must be on a stable highly active antiretroviral therapy (haart) regimen for 4 weeks prior to screening, in part 2 participants with screening cd4+ cell count \<350 cells/mcl must also be on a stable haart regimen for 4 weeks prior to screening exclusion criteria: * has received any candidate ebola vaccine * diagnosed with ebola virus disease, or prior exposure to ebov, including travel to epidemic ebola areas less than 1 month prior to screening * has received any experimental candidate ad26- or mva-based vaccine in the past or received any other investigational drug or investigational vaccine or used an invasive investigational medical device within 3 months prior to screening * known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products * presence of significant conditions (eg, history of seizure disorders, (auto)immune disease or deficiency, any spleen disease, active malignancy, ongoing tuberculosis treatment, other systemic infections) or clinically significant findings during screening of medical history, ecg (only in participants \>50 years), physical examination, vital signs or laboratory testing for which, in the opinion of the investigator, participation would not be in the best interest of the participants (eg, compromise the safety or well-being) or that could prevent, limit, or confound the protocol-specified assessments

Keywords: healthy vaccine ebola viruses ebola virus disease (evd) filoviruses hemorrhagic fever monovalent vaccine human adenovirus serotype 26 (ad26) encoding the ebola virus mayinga variant glycoprotein (ad26.zebov) modified vaccinia virus ankara - bavarian nordic (mva-bn) filo-vector safety immunogenicity