VRC 208: Dose, Safety and Immunogenicity of a Recombinant Modified Vaccinia Virus Ankara Ebola Vaccine, VRC-EBOMVA079-00-VP (MVA-EbolaZ), Administered Alone or as a Boost to cAd3-Ebola Vaccines in Healthy Adults

NCT02408913 | Completed Phase 1

• 2 other identifiers: 15010715-I-0107
• Study Type: interventional
• Target: 140
• Locations: 1 country
• Sites: 3

Brief Summary

Background: \- Ebola virus is a rare disease that starts with fever and muscle aches, but can lead to death. The 2014 Ebola outbreak in West Africa is the largest to date. There are no approved treatments for Ebola. Researchers want to see if two new vaccines VRC-EBOMVA079-00-VP (MVA-EbolaZ) and VRC-EBOADC069-00VP ( cAd3-EBO ) are safe and able to induce an immune response against Ebola. Objectives: \- To see if the two new vaccines are safe and if they cause any side effects. Also, to study immune responses to the vaccines. Eligibility: \- Healthy adults ages 18-66 Design:

• Participants will get one or two study vaccine injections depending on the study group they are assigned to. Each injection will repeat the same schedule:
• A needle and syringe will inject the vaccine into an upper arm muscle.
• 1-2 days later, participants must call the clinic to report how they feel.
• For 7 days they will check their temperature with a thermometer given to them. They will look at the injection site, and measure any redness or swelling with a ruler. They will write down any symptoms they have.
• In the first 2 months, participants will have at least 6 clinic visits and 1 phone contact. At each visit, participants will be checked for health changes or problems. They will tell how they feel and if they have taken any medications. Blood and urine samples may be collected.
• Participants might need to have extra clinic visits and laboratory tests if they have health changes that need to be checked.

Conditions

Healthy Adult Immune Responses to Vaccine

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Local and systemic reactogenicity signs and symptoms.

  Daily for 7 days following the vaccination

• Occurrence of adverse events of all severities.

  Through 4 weeks after each injection

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

  Through 48 weeks after last injection

Secondary Outcomes (2)

• Antibody responses as measured by ELISA and neutralization assays.

  4 weeks after vaccination.

• T cell responses as measured by intracellular cytokine staining (ICS)assay.

  4 weeks after vaccination.

Study Arms (4)

Group 2

EXPERIMENTAL

MVA-EbolaZ 1x10(8) PFU

Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)

Group 3

EXPERIMENTAL

cAd3-EBO 2x10(11) PU followed by MVAEbolaZ 1x10(8) PFU at 8 weeks

Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ); Biological: VRC-EBOADC069-00-VP (cAd3-EBO)

Group1

EXPERIMENTAL

MVA-EbolaZ 1x10(7) PFU

Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)

Groups 4 to 7

EXPERIMENTAL

MVA-EbolaZ 1x10(8) PFU administered in VRC 208 to participants who received cAd3-EBO or cAd3-EBOZ in VRC 207.

Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)

Interventions

VRC-EBOMVA079-00-VP (MVA-EbolaZ) BIOLOGICAL

Ebola Modified Vaccinia Virus Ankara Vaccine

Group 2; Group 3; Group1; Groups 4 to 7

VRC-EBOADC069-00-VP (cAd3-EBO) BIOLOGICAL

Ebola Chimpanzee Adenovirus Vector Vaccine

Group 3

Eligibility Criteria

• Age: 18 Years - 66 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 be eligible:
• to 50 years old.
• Available for clinical follow-up through the last study 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.
• Laboratory Criteria within 56 days prior to enrollment:
• Hemoglobin within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
• White blood cells (WBC) = 3,300-12,000 cells/mm(3).
• WBC differential either within institutional normal range or accompanied by the PI or designee approval.
• Total lymphocyte count greater than or equal to 800 cells/mm(3).
• Platelets = 125,000-400,000/mm(3).
• Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal.

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 Marburg vaccine in a prior clinical trial.
• Investigational Ebola vaccine in a prior clinical trial.
• Investigational cAd3 or MVA vaccines in a prior clinical trial.
• Evidence of increased cardiovascular disease risk defined as \>10% five year risk by the non-laboratory method.
• Electrocardiogram (ECG) with clinically significant abnormalities (examples may include: pathologic Q waves, significant ST-T wave changes, left ventricular hypertrophy, any non-sinus rhythm excluding isolated premature atrial contractions, right or left bundle branch block, advanced A-V heart block). ECG abnormalities determined by a cardiologist to be clinically insignificant as related to study participation do not preclude study enrollment.
• Type 1 hypersensitivity reaction to aminoglycoside antibiotics.
• More than 10 days of systemic immunosuppressive medications except for short-term treatments of minor ailments in otherwise healthy volunteers, or cytotoxic medications within the 4 weeks prior to enrollment, or any within the 14 days 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.
• Medically indicated subunit or killed vaccines, e.g. influenza, pneumococcal within 2 weeks of initial study vaccine administration unless approved by the study Principal Investigator (PI) or designee
• Current anti-tuberculosis prophylaxis or therapy.
• Female-specific criteria:

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, Baltimore

Baltimore, Maryland, 21201-1595, United States

Location

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Stanley DA, Honko AN, Asiedu C, Trefry JC, Lau-Kilby AW, Johnson JC, Hensley L, Ammendola V, Abbate A, Grazioli F, Foulds KE, Cheng C, Wang L, Donaldson MM, Colloca S, Folgori A, Roederer M, Nabel GJ, Mascola J, Nicosia A, Cortese R, Koup RA, Sullivan NJ. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nat Med. 2014 Oct;20(10):1126-9. doi: 10.1038/nm.3702. Epub 2014 Sep 7.

  PMID: 25194571 BACKGROUND

• 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 BACKGROUND

• 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: 25540891 BACKGROUND

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: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2015
• First Posted: April 6, 2015
• Study Start: March 26, 2015
• Primary Completion: April 6, 2017
• Study Completion: April 6, 2017
• Last Updated: April 11, 2019

Record last verified: 2017-04-06

Locations

US (3)