NCT02354404

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
90

participants targeted

Target at P75+ for phase_1

Timeline
Completed

Started Jan 2015

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 27, 2015

Completed
2 days until next milestone

First Submitted

Initial submission to the registry

January 29, 2015

Completed
5 days until next milestone

First Posted

Study publicly available on registry

February 3, 2015

Completed
2.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 19, 2017

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

April 19, 2017

Completed
Last Updated

December 5, 2017

Status Verified

September 1, 2017

Enrollment Period

2.2 years

First QC Date

January 29, 2015

Last Update Submit

December 1, 2017

Conditions

Hemorrhagic Fever, Ebola

Keywords

Ebola virusFiloviridae InfectionsHemorrhagic Fever, EbolaViral DiseasesHemorrhagic Fevers, Viral

Outcome Measures

Primary Outcomes (4)

  • Incidence of solicited adverse events after vaccination

    Incidence is reported for solicited events for 7 days after each vaccination.

    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.

    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.

    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.

    28 days after each vaccination

Secondary Outcomes (3)

  • Antibody response to Ebola GP as measured by ELISA

    4 weeks after each vaccination

  • Antibody response to Ebola GP as measured by neutralization assay

    4 weeks after vaccination

  • T cell immune response measured by intracellular cytokine staining (ICS)

    4 weeks after vaccination

Study Arms (6)

Group 1a: cAd3-EBOZ at 1x10(10) PU

EXPERIMENTAL

Part 1: cAd3-EBOZ at 1x10(10) PU intramuscularly at Day 0; Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOZBiological: MVA-EbolaZ

Group 1b: cAd3-EBOZ at 1x10(11) PU

EXPERIMENTAL

Part 1: cAd3-EBOZ at 1x10(11) PU intramuscularly at Day 0; Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOZBiological: MVA-EbolaZ

Group 1c: cAd3-EBO at 2x10(10) PU

EXPERIMENTAL

Part 1: cAd3-EBO at 2x10(10) PU intramuscularly at Day 0; Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOBiological: MVA-EbolaZ

Group 1d: cAd3-EBO at 2x10(11) PU

EXPERIMENTAL

Part 1: cAd3-EBO at 2x10(11) PU intramuscularly at Day 0; Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOBiological: MVA-EbolaZ

Group 2a:cAd3-EBO at 2x10(10) PU

EXPERIMENTAL

Part 1: cAd3-EBO at 2x10(10) PU intramuscularly at Day 0 (as a boost to prior receipt of the Ebola DNA WT vaccine); Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOBiological: MVA-EbolaZ

Group 2b: cAd3-EBO at 2x10(11) PU

EXPERIMENTAL

Part 1: cAd3-EBO at 2x10(11) PU intramuscularly at Day 0 (as a boost to prior receipt of the Ebola DNA WT vaccine); Part 2: Option to receive MVA-EbolaZ at 1x10(8) PFU intramuscularly after Study Week 36 as a boost to the Part 1 study vaccination

Biological: cAd3-EBOBiological: MVA-EbolaZ

Interventions

cAd3-EBOZBIOLOGICAL

cAd3 vaccine vector expressing Ebola glycoprotein from the Zaire strain in single dose vials at 1x10(11) PU/mL.

Also known as: VRC-EBOADC076-00-VP
Group 1a: cAd3-EBOZ at 1x10(10) PUGroup 1b: cAd3-EBOZ at 1x10(11) PU
cAd3-EBOBIOLOGICAL

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 \[2x10(11) PU/mL total\].

Also known as: VRC-EBOADC069-00-VP
Group 1c: cAd3-EBO at 2x10(10) PUGroup 1d: cAd3-EBO at 2x10(11) PUGroup 2a:cAd3-EBO at 2x10(10) PUGroup 2b: cAd3-EBO at 2x10(11) PU
MVA-EbolaZBIOLOGICAL

MVA vaccine vector that expresses Ebola glycoprotein from the Zaire strain in single dose vials at 3.2 x 10(8) PFU/mL

Also known as: VRC-EBOMVA079-00-VP
Group 1a: cAd3-EBOZ at 1x10(10) PUGroup 1b: cAd3-EBOZ at 1x10(11) PUGroup 1c: cAd3-EBO at 2x10(10) PUGroup 1d: cAd3-EBO at 2x10(11) PUGroup 2a:cAd3-EBO at 2x10(10) PUGroup 2b: cAd3-EBO at 2x10(11) PU

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • A volunteer subject must meet all of the following criteria:
  • to 65 years old.
  • Available for clinical follow-up through Week 48.
  • Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  • Must be willing to be taken home at enrollment visit and allow home visits if participant does not keep appointments
  • Must complete an Assessment of Understanding successfully.
  • Able to read (English or Luganda) and willing to complete the informed consent process.
  • Willing to donate blood for sample storage to be used for future research.
  • In good general health without clinically significant medical history.
  • Physical examination and laboratory results without clinically significant findings and a body mass index (BMI) ≤ 40 within the 56 days prior to enrollment.
  • Hemoglobin ≥ 11.0 g/dL for women; ≥12.5 g/dL for men.
  • White blood cells (WBC) = 2,500-12,000 cells/mm3.
  • WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
  • Total lymphocyte count ≥ 800 cells/mm3.
  • Platelets = 125,000 - 400,000/mm3.
  • +7 more criteria

You may not qualify if:

  • Volunteer has received any of the following substances:
  • Investigational Ebola or Marburg vaccine (other than the Ebola DNA vaccine delivered in RV 247) in a prior clinical trial or prior receipt of a cAd3 adenoviral vectored investigational vaccine.
  • Chronic use of immunomodulators and systemic glucocorticoids in daily doses of glucocorticoid equivalence \> 20 mg of prednisolone, for periods exceeding 10 days. Non-steroidal anti-inflammatory drugs \[NSAIDS\] are permitted.
  • Participants that have used less than the stated glucocorticoid dose may still be excluded at the Investigator's discretion.
  • Blood products within 112 days prior to enrollment.
  • Investigational research agents within 28 days prior to enrollment.
  • Live attenuated vaccines within 28 days prior to enrollment.
  • Subunit or killed vaccines within 14 days prior to enrollment.
  • Current anti-tuberculosis prophylaxis or therapy.
  • Woman who is breast-feeding or planning to become pregnant during the first 24 weeks after study vaccine administration.
  • Volunteer has a history of any of the following clinically significant conditions:
  • Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
  • Clinically significant autoimmune disease or immunodeficiency.
  • Asthma that is not well controlled.
  • Diabetes mellitus (type I or II), with the exception of gestational diabetes.
  • +16 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Makerere University Walter Reed Project

Kampala, Uganda

Location

Related Publications (3)

  • Kibuuka H, Berkowitz NM, Millard M, Enama ME, Tindikahwa A, Sekiziyivu AB, Costner P, Sitar S, Glover D, Hu Z, Joshi G, Stanley D, Kunchai M, Eller LA, Bailer RT, Koup RA, Nabel GJ, Mascola JR, Sullivan NJ, Graham BS, Roederer M, Michael NL, Robb ML, Ledgerwood JE; RV 247 Study Team. Safety and immunogenicity of Ebola virus and Marburg virus glycoprotein DNA vaccines assessed separately and concomitantly in healthy Ugandan adults: a phase 1b, randomised, double-blind, placebo-controlled clinical trial. Lancet. 2015 Apr 18;385(9977):1545-54. doi: 10.1016/S0140-6736(14)62385-0. Epub 2014 Dec 23.

    PMID: 25540891BACKGROUND

  • Ledgerwood JE, DeZure AD, Stanley DA, Coates EE, Novik L, Enama ME, Berkowitz NM, Hu Z, Joshi G, Ploquin A, Sitar S, Gordon IJ, Plummer SA, Holman LA, Hendel CS, Yamshchikov G, Roman F, Nicosia A, Colloca S, Cortese R, Bailer RT, Schwartz RM, Roederer M, Mascola JR, Koup RA, Sullivan NJ, Graham BS; VRC 207 Study Team. Chimpanzee Adenovirus Vector Ebola Vaccine. N Engl J Med. 2017 Mar 9;376(10):928-938. doi: 10.1056/NEJMoa1410863. Epub 2014 Nov 26.

    PMID: 25426834BACKGROUND

  • Sarwar UN, Costner P, Enama ME, Berkowitz N, Hu Z, Hendel CS, Sitar S, Plummer S, Mulangu S, Bailer RT, Koup RA, Mascola JR, Nabel GJ, Sullivan NJ, Graham BS, Ledgerwood JE; VRC 206 Study Team. Safety and immunogenicity of DNA vaccines encoding Ebolavirus and Marburgvirus wild-type glycoproteins in a phase I clinical trial. J Infect Dis. 2015 Feb 15;211(4):549-57. doi: 10.1093/infdis/jiu511. Epub 2014 Sep 14.

    PMID: 25225676BACKGROUND

MeSH Terms

Conditions

Hemorrhagic Fever, EbolaFiloviridae InfectionsVirus DiseasesHemorrhagic Fevers, Viral

Condition Hierarchy (Ancestors)

RNA Virus InfectionsInfectionsMononegavirales Infections

Study Officials

  • Merlin Robb, MD

    US Military HIV Research Program

    STUDY CHAIR

  • Julie Ledgerwood, DO

    VRC, NIAID, NIH

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 29, 2015

First Posted

February 3, 2015

Study Start

January 27, 2015

Primary Completion

April 19, 2017

Study Completion

April 19, 2017

Last Updated

December 5, 2017

Record last verified: 2017-09

Locations

UG(1)