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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
90
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
Makerere University Walter Reed Project
Kampala, Uganda
Incidence of solicited adverse events after vaccination
Incidence is reported for solicited events for 7 days after each vaccination.
Time frame: 7 days
Incidence of unsolicited adverse events of any severity 28 days after vaccination
Incidence is reported for unsolicited events for 28 days after each vaccination. The reporting period is Day 0 to Day 28.
Time frame: 28 days
Incidence of serious adverse events or new chronic medical conditions through the last study visit
Incidence is reported of serious adverse events and new chronic medical conditions for 48 weeks after vaccination.
Time frame: From first study injection through 48 weeks after final study injection
Mean change from baseline in safety laboratory measures
At Days 2 or 3, 14, and 28 blood will be drawn to measure safety measures that many include complete blood count (CBC), creatinine, ALT, PT and PTT.
Time frame: 28 days after each vaccination
Antibody response to Ebola GP as measured by ELISA
Blood is collected at baseline and 4 weeks after vaccination
Time frame: 4 weeks after each vaccination
Antibody response to Ebola GP as measured by neutralization assay
Blood is collected at baseline and 4 weeks after vaccination
Time frame: 4 weeks after vaccination
T cell immune response measured by intracellular cytokine staining (ICS)
Blood is collected at baseline and 4 weeks after vaccination
Time frame: 4 weeks after vaccination
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