Clinical Trial of Ebola Vaccines cAd3-EBO, cAd3-EBOZ and MVA-EbolaZ in Healthy Adults in Uganda
Condition: Hemorrhagic Fever, Ebola
MeSH terms: Hemorrhagic Fever, Ebola; Hemorrhagic Fevers, Viral
Study type: Interventional
Phase: Phase 1

Summary: 
      Phase Ib study in 90 healthy adults,18 years to 65 years of age, to evaluate the safety,
      tolerability and immunogenicity of the VRC-EBOADC069-00-VP (cAd3-EBO) and VRC-EBOADC076-00-VP
      (cAd3-EBOZ) investigational Ebola vaccines in Part 1 and boosting with the
      VRC-EBOMVA079-00-VP (MVA-EbolaZ) investigational Ebola vaccine in Part 2.

      Part 1: Randomizations to cAd3-EBO or cAd3-EBOZ at two different dose levels within Group 1
      will include at least 60 volunteers who have never received an investigational Ebola vaccine.
      Randomizations to cAd3-EBO at two different dose levels within Group 2 may include up to 30
      eligible participants who previously participated in the RV247 vaccine clinical trial and
      received the investigational VRC-EBODNA023-00-VP (Ebola DNA WT) vaccine.

      Part 2: Participants in Part 1 may receive a booster vaccination with the MVA-EbolaZ vaccine
      at the same dose level.
    

Detailed description: 
      Study Design: This Phase 1b, open-label study to examine safety, tolerability and
      immunogenicity of investigational Ebola vaccines is conducted in two Parts. In Part 1
      subjects are randomized to receive either the cAd3-EBO or cAd3-EBOZ vaccine at two different
      dose levels. In Part 2, participants from Part 1 may receive a booster injection with the
      MVA-EbolaZ vaccine; all at the same dose level. The hypotheses are that the study vaccines,
      cAd3-EBO, cAd3-EBOZ and MVA-EbolaZ, will be safe and will elicit immune responses to Ebola
      glycoprotein (GP). The primary objectives are to evaluate the safety and tolerability of the
      study vaccines administered as intramuscular (IM) injections. The secondary objectives are
      related to immunogenicity.

      Study Products 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 2x10(11) particle
      units (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 1x10(11) PU/mL.

      VRC-DILADC065-00-VP (diluent) is the vaccine formulation buffer and will be used when needed
      to prepare the correct dosage of cAd3-EBO or cAd3-EBOZ.

      VRC-EBOMVA079-00-VP (MVA-EbolaZ) is composed of a MVA vector that expresses Ebola WT GP from
      the Zaire strain. It is formulated at 3.2x10(8) PFU/mL.

      Part 1 Study Plan:

      Group 1: 60 volunteers will be randomized: 15 in each of the two dosage groups for
      VRC-EBOADC069-00-VP [2x10(10) PU or 2x10(11) PU] and 15 in each of the two dosage groups for
      VRC-EBOADC076-00-VP [1x10(10) PU or 1x10(11) PU].

      Group 2: up to 30 volunteers that previously participated in the RV 247 clinical trial who
      received the investigational product VRC-EBODNA023-00-VP will be randomized to receive one of
      the two dosage groups for VRC-EBOADC069-00-VP.

      The two groups will be enrolled simultaneously. If less then 30 participants enroll into
      Group 2, additional participants may be enrolled into Group 1 for a total of 90 participants
      overall. Participants will be evaluated by 9 clinic visits over 48 weeks.

      Part 2 Study Plan:

      Part 1 participants who received a study vaccination and have completed at least 36 weeks of
      follow-up, who are eligible and consent may receive a booster injection with the
      VRC-EBOMVA079-00-VP vaccine at 1x10(8) particle forming units (PFU). Participants will be
      evaluated by 11 clinic visits over 48 weeks after beginning Part 2.
    

Intervention name(s): cAd3-EBOZ; cAd3-EBO; MVA-EbolaZ
Intervention type(s): Biological; Biological; Biological
Intervention description(s): cAd3 vaccine vector expressing Ebola glycoprotein from the Zaire strain in single dose vials at 1x10(11) PU/mL.; 1:1 ratio of cAd3 vaccine vectors expressing Ebola glycoprotein from the Zaire and Sudan strains filled into single dose vials at 1x10(11) PU/mL of each [2x10(11) PU/mL total].; MVA vaccine vector that expresses Ebola glycoprotein from the Zaire strain in single dose vials at 3.2 x 10(8) PFU/mL
Other intervention name(s): VRC-EBOADC076-00-VP; VRC-EBOADC069-00-VP; VRC-EBOMVA079-00-VP
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Ebola virus; Filoviridae Infections; Hemorrhagic Fever, Ebola; Viral Diseases; Hemorrhagic Fevers, Viral