a study to assess safety, tolerability, and immunogenicity of three heterologus 2-dose regimens of the candidate prophylactic vaccines for ebola in healthy adults

Conditions: Ebola Viral Disease

Summary: the purpose of this study is to evaluate the safety, tolerability, and immunogenicity of 3 vaccination schedules of ad26.zebov and mva-bn-filo administered intramuscularly (im) as 2-dose heterologous regimens.

this is a randomized, observer-blind, placebo-controlled, parallel-group, multicenter, phase 2 study evaluating the safety, tolerability and immunogenicity of 2-dose heterologous regimens using ad26.zebov and mva-bn-filo administered to healthy adults participants in europe. the study involves a screening period of up to 12 weeks, a vaccination period in which participants will be vaccinated with ad26.zebov (dose 1) followed by vaccination with mva-bn-filo (dose 2) 28, 56 or 84 days later, and a post-vaccination phase until 6 months post dose 2 visit (days 209, 237 or 265). after unblinding, only participants who received ad26.zebov and/or mva-bn-filo will continue the study until the day 365 visit (or until the start of the roll-over study or for an additional 12 months \[whichever comes first\] for participants in france who agree to continue the long-term follow-up after day 365) to assess long-term safety and immunogenicity. participants will enroll into 3 cohorts: that is, cohort 1 (participants will receive ad26.zebov and mva-bn-filo in an open-label fashion), cohort 2 (participants will be randomized to receive the 2-dose heterologous vaccine regimen with either ad26.zebov followed by mva-bn-filo, or placebo in a 14:1 ratio) and cohort 3 (participants will be randomized to receive the 2-dose heterologous vaccine regimen with either ad26.zebov followed by mva-bn-filo, or placebo in a 10:3 ratio). in cohorts 2 and 3, core immunogenicity assessments (humoral and cellular assays) will be performed. in cohort 2, additional immunogenicity assessments will be done. in cohort 1, plasma blast response kinetics will be evaluated. safety will be monitored during the study.

Eligibility criteria:
inclusion criteria: * must be healthy in the investigator's clinical judgment on the basis of medical history, physical examination, electrocardiogram (ecg) and vital signs performed at screening * must be healthy on the basis of clinical laboratory tests performed at screening. if the results of the laboratory screening tests are outside the 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 * before randomization, a woman must be either of childbearing potential and practicing (or intending to practice) a highly effective method of birth control consistent with local regulations regarding the use of birth control methods for participants participating in clinical studies, beginning at least 28 days prior to vaccination or not of childbearing potential: postmenopausal (greater than \[\>\] 45 years of age with amenorrhea for at least 2 years or lesser than or equal to \[\ 40 international unit per milliliter \[iu/l\]); permanently sterilized (for example, bilateral tubal occlusion \[which includes tubal ligation procedures as consistent with local regulations\], hysterectomy, bilateral salpingectomy, bilateral oophorectomy); or otherwise be incapable of pregnancy * woman of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hcg\]) at screening and a negative urine beta-hcg pregnancy test immediately prior to each study vaccine administration * man who is sexually active with a woman of childbearing potential and has not had a vasectomy performed more than 1 year prior to screening must be willing to use condoms for sexual intercourse beginning prior to enrollment exclusion criteria: * having received any candidate ebola vaccine * diagnosed with ebola virus disease, or prior exposure to ebola virus, including travel to west africa less than 1 month prior to screening. west africa includes but is not limited to the countries of guinea, liberia, mali, and sierra leone * having received any experimental candidate adenovirus serotype 26 (vector: ad26) or modified vaccinia ankara (mva-) based vaccine in the past * known allergy or history of anaphylaxis or other serious adverse reactions to vaccines or vaccine products (including any of the constituents of the study vaccines including known allergy to egg, egg products and aminoglycosides * presence of acute illness or temperature greater than or equal to 38.0 c on day 1

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