Safety, Tolerability, and Immunogenicity of the Ebola Chimpanzee Adenovirus Vector Vaccine (cAd3-EBO), VRC-EBOADC069-00-VP, in Healthy Adults

Study Design: This is a Phase 1/1b, open-label study to examine safety, tolerability and immunogenicity of investigational Ebola vaccines in healthy adults. Part 1 is a Phase 1 dose escalation of the cAd3-EBO vaccine that encodes wild type (WT) glycoproteins (GP) from Zaire and Sudan strains of Ebolavirus. Part 2 is a Phase 1b further evaluation of the cAd3-EBO vaccine at the highest dose and evaluation of the Zaire component, which will be provided as a vaccine designated cAd3-EBOZ. The hypotheses are that the study vaccines, cAd3-EBO and cAd3-EBOZ, will be safe and will elicit immune responses to Ebola GP. The primary objectives are to evaluate the safety and tolerability of the study vaccines administered as single intramuscular (IM) injections at two dose levels. The secondary objectives are related to evaluation of the immunogenicity. Product Description: VRC-EBOADC069-00-VP (cAd3-EBO) is composed of two recombinant cAd3 vectors in a 1:1 ratio that express Ebola WT GPs from Zaire and Sudan strains. It is formulated at 2 times 10(11) PU/mL. VRC-EBOADC076-00-VP (cAd3-EBOZ) is composed of a cAd3 vector that expresses Ebola WT GP from the Zaire strain. It is formulated at 1 times 10(11) PU/mL. VRC-DILADC065-00-VP (diluent) is the formulation buffer used for vaccine production and will be used when needed to prepare the correct dosage of cAd3-EBO and cAd3-EBOZ. Subjects: Part 1: Healthy adult volunteers, 18 to 50 years old; Part 2: Healthy adult volunteers, 18 to 65 years old. Study Plan: Part 1: 20 subjects will be enrolled, with 10 in each of the two dosage groups for cAd3-EBO. The dose escalation plan includes daily review of any new safety data by a study clinician, weekly review of safety data by the protocol team and a staged enrollment plan with required interim safety reviews before proceeding to the next step. The study plan includes no more than one enrollment per day for the first 3 vaccinated subjects in each group. After at least 3 days of follow-up, an interim safety review will occur before enrollment of additional subjects into the group. When there are at least 2 weeks of follow-up safety data for the first 3 vaccinated subjects in Group 1, an interim safety review will occur before proceeding to the next dose level. Part 2: About 130 subjects will be enrolled as shown in the Schema table. Group 3 is open only to subjects who received Ebola DNA WT vaccine in protocol VRC 206 to receive cAd3-EBO as a booster vaccine at the 2 times 10(11) PU dose. Group 4 is for randomization of subjects to two dosage groups of cAd3-EBOZ. Group 5 is for further evaluation of the cAd3-EBO vaccine at the 2 times 10(11) PU dose. Study Duration: Subjects will be evaluated by 9 clinic visits over 48 weeks.