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

NCT02231866 | Completed Phase 1

• 2 other identifiers: 14018314-I-0183
• Study Type: interventional
• Target: 143
• Locations: 1 country
• Sites: 3

Brief 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.

Conditions

Healthy Adult Immune Responses to Vaccine

Keywords

Filovirus; Healthy; Ebola Hemorrhagic Fever; Immunity; Ebola Virus

Outcome Measures

Primary Outcomes (3)

• Solicited systemic and local reactogenicity signs and symptoms.

  Daily for 7 days following each vaccination.

• Occurrence of adverse events of all severities.

  Through 4 weeks after the vaccination.

• Occurrence of serious adverse events and new chronic medical conditions.

  Through 48 weeks after the vaccination.

Secondary Outcomes (2)

• Antibody responses as measured by ELISA and neutralization assays

  4 weeks after vaccination

• T cell immune responses as measure by intracellular cytokine staining (ICS)

  4 weeks after vaccination

Study Arms (6)

Group 1

EXPERIMENTAL

cAd3-EBO at 2x10(10)PU IM

Biological: VRC-EBOADC069-00-VP

Group 2

EXPERIMENTAL

cAd3-EBO at 2x10(11)PU IM

Biological: VRC-EBOADC069-00-VP

Group 3

EXPERIMENTAL

cAd3-EBO at 2x10(11)PU IM boost of Ebola DNA WT vaccine (VRC 206 participants)

Biological: VRC-EBOADC069-00-VP

Group 4A

EXPERIMENTAL

cAd3-EBOZ at 1x10(10)PU IM

Biological: VRC-EBOADC076-00-VP

Group 4B

EXPERIMENTAL

cAd3-EBOZ at 1x10(11)PU IM

Biological: VRC-EBOADC076-00-VP

Group 5

EXPERIMENTAL

cAd3-EBO at 2x10(11)PU IM

Biological: VRC-EBOADC069-00-VP

Interventions

VRC-EBOADC069-00-VP BIOLOGICAL

cAd3-EBO Ebola Chimpanzee Adenovirus Vector Vaccine GP Zaire + GP Sudan

Group 1; Group 2; Group 3; Group 5

VRC-EBOADC076-00-VP BIOLOGICAL

cAd3-EBO Ebola Chimpanzee Adenovirus Vector Vaccine GP Zaire

Group 4A; Group 4B

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A volunteer must meet all of the following criteria:
• to 50 years old for Groups 1 and 2; 18 to 65 years old for Groups 3, 4, and 5.
• Available for clinical follow-up through Week 48 after enrollment for groups 1-4 and through at least Week 4 after enrollment for group 5, with no planned travel that would preclude completion of the Study Week 4 visit.
• Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
• Able 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) less than or equal to 40 within the 56 days prior to enrollment.
• For Group 3 volunteers only, must have received the VRC-EBODNA023-00-VP (Ebola DNA WT) vaccine in the VRC 206 study.
• Laboratory Criteria within 56 days prior to enrollment:
• Hemoglobin greater than or equal to 11.5 g/dL for women; greater than or equal to 13.0 g/dL for men.
• White blood cells (WBC) = 3,300-12,000 cells/mm(3).
• WBC differential either within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
• Total lymphocyte count greater than or equal to 800 cells/mm(3).
• Platelets = 125,000 400,000/mm(3).

You may not qualify if:

• A volunteer will be excluded if one or more of the following conditions apply:
• Volunteer has received any of the following substances:
• Investigational Ebola or Marburg vaccine in a prior clinical trial (except for Group 3 volunteers) or prior receipt of a cAd3 adenoviral vectored investigational vaccine.
• Immunosuppressive medications within 2 weeks prior to enrollment.
• Blood products within 112 days (16 weeks) prior to enrollment.
• Investigational research agents within 28 days (4 weeks) prior to enrollment.
• Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.
• Subunit or killed vaccines within 14 days (2 weeks) prior to enrollment.
• Current anti-tuberculosis prophylaxis or therapy.
• Female-specific criteria:
• 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.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (3)

Hope Clinic - Emory Vaccine Ctr

Decatur, Georgia, 30030, United States

Location

University of Maryland Center for Vaccine Development

Baltimore, Maryland, 21201-1595, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Ledgerwood JE, Costner P, Desai N, Holman L, Enama ME, Yamshchikov G, Mulangu S, Hu Z, Andrews CA, Sheets RA, Koup RA, Roederer M, Bailer R, Mascola JR, Pau MG, Sullivan NJ, Goudsmit J, Nabel GJ, Graham BS; VRC 205 Study Team. A replication defective recombinant Ad5 vaccine expressing Ebola virus GP is safe and immunogenic in healthy adults. Vaccine. 2010 Dec 16;29(2):304-13. doi: 10.1016/j.vaccine.2010.10.037. Epub 2010 Oct 27.

  PMID: 21034824 BACKGROUND

• Martin JE, Sullivan NJ, Enama ME, Gordon IJ, Roederer M, Koup RA, Bailer RT, Chakrabarti BK, Bailey MA, Gomez PL, Andrews CA, Moodie Z, Gu L, Stein JA, Nabel GJ, Graham BS. A DNA vaccine for Ebola virus is safe and immunogenic in a phase I clinical trial. Clin Vaccine Immunol. 2006 Nov;13(11):1267-77. doi: 10.1128/CVI.00162-06. Epub 2006 Sep 20.

  PMID: 16988008 BACKGROUND

• Kuhn JH, Bao Y, Bavari S, Becker S, Bradfute S, Brister JR, Bukreyev AA, Chandran K, Davey RA, Dolnik O, Dye JM, Enterlein S, Hensley LE, Honko AN, Jahrling PB, Johnson KM, Kobinger G, Leroy EM, Lever MS, Muhlberger E, Netesov SV, Olinger GG, Palacios G, Patterson JL, Paweska JT, Pitt L, Radoshitzky SR, Saphire EO, Smither SJ, Swanepoel R, Towner JS, van der Groen G, Volchkov VE, Wahl-Jensen V, Warren TK, Weidmann M, Nichol ST. Virus nomenclature below the species level: a standardized nomenclature for natural variants of viruses assigned to the family Filoviridae. Arch Virol. 2013 Jan;158(1):301-11. doi: 10.1007/s00705-012-1454-0. Epub 2012 Sep 23.

  PMID: 23001720 BACKGROUND

• Tapia MD, Sow SO, Lyke KE, Haidara FC, Diallo F, Doumbia M, Traore A, Coulibaly F, Kodio M, Onwuchekwa U, Sztein MB, Wahid R, Campbell JD, Kieny MP, Moorthy V, Imoukhuede EB, Rampling T, Roman F, De Ryck I, Bellamy AR, Dally L, Mbaya OT, Ploquin A, Zhou Y, Stanley DA, Bailer R, Koup RA, Roederer M, Ledgerwood J, Hill AVS, Ballou WR, Sullivan N, Graham B, Levine MM. Use of ChAd3-EBO-Z Ebola virus vaccine in Malian and US adults, and boosting of Malian adults with MVA-BN-Filo: a phase 1, single-blind, randomised trial, a phase 1b, open-label and double-blind, dose-escalation trial, and a nested, randomised, double-blind, placebo-controlled trial. Lancet Infect Dis. 2016 Jan;16(1):31-42. doi: 10.1016/S1473-3099(15)00362-X. Epub 2015 Nov 4.

  PMID: 26546548 DERIVED

• 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: 25426834 DERIVED

MeSH Terms

Conditions

Hemorrhagic Fever, Ebola

Condition Hierarchy (Ancestors)

Hemorrhagic Fevers, Viral; RNA Virus Infections; Virus Diseases; Infections; Filoviridae Infections; Mononegavirales Infections

Study Officials

• Julie E Ledgerwood, D.O.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: September 3, 2014
• First Posted: September 4, 2014
• Study Start: August 27, 2014
• Primary Completion: April 5, 2017
• Study Completion: April 5, 2017
• Last Updated: July 5, 2018

Record last verified: 2017-04-05

Locations

US (3)