Safety, Tolerability, and Immunogenicity of the Ebola Chimpanzee Adenovirus Vector Vaccine (cAd3-EBO), VRC-EBOADC069-00-VP, in Healthy Adults
Condition: Healthy Adult Immune Responses to Vaccine
MeSH terms: Adenoviridae Infections
Study type: Interventional
Phase: Phase 1

Summary: 
      Background:

      - Ebola virus causes an infection known as Ebola virus disease (EVD). This it is generally a
      severe disease which can also lead to death. The 2014 outbreak of EVD in West Africa is the
      largest ever. Researchers want to develop a vaccine to prevent Ebola infection. It is
      impossible for someone to get an Ebola infection from this vaccine.

      Objectives:

      - To see if an Ebola vaccine is safe and to study immune responses to it.

      Eligibility:

      - Healthy adults ages 18-65.

      Design:

        -  Participants will be screened through a separate protocol.

        -  Participants will receive the vaccine injection by needle and syringe into an upper arm
           muscle. - Participants will stay at the clinic for 3 hours after the injection.

        -  About 2 days later, participants must speak with clinic staff about how they are doing.

        -  Every day for 7 days after the injection, participants will record their temperature and
           symptoms and look at the injection site. They will get a thermometer and a ruler to
           measure any redness or swelling. They will report any side effects.

        -  In the first 2 months in the study, participants will have at least 6 clinic visits and
           1 phone call. They will have at least 3 other visits over the next 9 months.

        -  At each visit, participants will be checked for health changes or problems since their
           last visit. They will be asked how they feel and if they have taken any medicine. Blood
           will be drawn at most visits. Urine samples may be collected.
    

Detailed description: 
      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.
    

Intervention name(s): VRC-EBOADC069-00-VP; VRC-EBOADC076-00-VP
Intervention type(s): Biological; Biological
Intervention description(s): cAd3-EBO Ebola Chimpanzee Adenovirus Vector Vaccine GP Zaire + GP Sudan; cAd3-EBO Ebola Chimpanzee Adenovirus Vector Vaccine GP Zaire
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Filovirus; Healthy; Ebola Hemorrhagic Fever; Immunity; Ebola Virus