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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

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ClinicalTrials.gov Identifier: NCT02408913
Recruitment Status : Completed
First Posted : April 6, 2015
Last Update Posted : April 11, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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.

Condition or disease Intervention/treatment Phase
Healthy Adult Immune Responses to Vaccine Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ) Biological: VRC-EBOADC069-00-VP (cAd3-EBO) Phase 1

Detailed Description:
This Phase 1/1b study will examine dose, safety, tolerability and immunogenicity of an investigational MVA-vectored Ebola vaccine in healthy adults. The vaccine encodes wild type (WT) glycoprotein (GP) from Zaire strain of Ebola and will be administered intramuscularly (IM) with needle and syringe. The safety and tolerability of the MVA-EbolaZ will be evaluated at escalating doses of 1x10(7) and 1x10(8) plaque forming units (PFU). Part 1 includes enrollment of vaccine-naive subjects to conduct a dose escalation of the MVA-EbolaZ vaccine and to evaluate the vaccine as a boost for the cAd3-EBO vaccine. In Part 2 of the study, up to 140 subjects who received the cAd3-EBO or cAd3-EBOZ vaccine in VRC 207 study will be boosted with MVA-EbolaZ. The hypotheses are that the study vaccines will be safe and elicit immune responses to Ebola GP, and that the prime-boost regimens will be safe and result in a more polyfunctional response to Ebola GP that is of greater magnitude and duration than response to either of the vaccines alone.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 140 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: VRC 208: Phase 1/1b Open-Label Clinical Trial to Evaluate Dose, Safety and Immunogenicity of Recombinant Modified Vaccinia Virus Ankara Ebola Vaccine,VRC-EBOMVA079-00-VP, Administered Alone or as Boost to cAd3-Ebola Vaccines in Healthy Adults
Study Start Date : March 26, 2015
Actual Primary Completion Date : April 6, 2017
Actual Study Completion Date : April 6, 2017

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Ebola

Arm Intervention/treatment
Experimental: Group 2
MVA-EbolaZ 1x10(8) PFU
Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)
Ebola Modified Vaccinia Virus Ankara Vaccine

Experimental: Group 3
cAd3-EBO 2x10(11) PU followed by MVAEbolaZ 1x10(8) PFU at 8 weeks
Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)
Ebola Modified Vaccinia Virus Ankara Vaccine

Biological: VRC-EBOADC069-00-VP (cAd3-EBO)
Ebola Chimpanzee Adenovirus Vector Vaccine

Experimental: Group1
MVA-EbolaZ 1x10(7) PFU
Biological: VRC-EBOMVA079-00-VP (MVA-EbolaZ)
Ebola Modified Vaccinia Virus Ankara Vaccine

Experimental: Groups 4 to 7
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)
Ebola Modified Vaccinia Virus Ankara Vaccine




Primary Outcome Measures :
  1. Local and systemic reactogenicity signs and symptoms. [ Time Frame: Daily for 7 days following the vaccination ]
  2. Occurrence of adverse events of all severities. [ Time Frame: Through 4 weeks after each injection ]
  3. Occurrence of serious adverse events and new chronic medical conditions. [ Time Frame: Through 48 weeks after last injection ]

Secondary Outcome Measures :
  1. Antibody responses as measured by ELISA and neutralization assays. [ Time Frame: 4 weeks after vaccination. ]
  2. T cell responses as measured by intracellular cytokine staining (ICS)assay. [ Time Frame: 4 weeks after vaccination. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 66 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:

Inclusion Criteria for Groups 1, 2, and 3.

A volunteer must meet all of the following criteria to be eligible:

  1. 18 to 50 years old.
  2. Available for clinical follow-up through the last study visit.
  3. Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process.
  4. Able and willing to complete the informed consent process.
  5. Willing to donate blood for sample storage to be used for future research.
  6. In good general health without clinically significant medical history.
  7. 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:

  8. Hemoglobin within institutional normal range or accompanied by the Principal Investigator (PI) or designee approval.
  9. White blood cells (WBC) = 3,300-12,000 cells/mm(3).
  10. WBC differential either within institutional normal range or accompanied by the PI or designee approval.
  11. Total lymphocyte count greater than or equal to 800 cells/mm(3).
  12. Platelets = 125,000-400,000/mm(3).
  13. Alanine aminotransferase (ALT) less than or equal to 1.25 times upper limit of normal.
  14. Serum creatinine less than or equal to 1.1 times upper limit of normal.
  15. Partial thromboplastin time (PTT) less than or equal to 1.1 times upper limit of normal or accompanied by the Principal Investigator (PI) or designee approval.
  16. Prothrombin time (PT) less than or equal to1.1 times upper limit of normal or accompanied by the Principal Investigator (PI) or designee approval.
  17. HIV-uninfected as evidenced by a negative FDA-approved HIV diagnostic blood test.

    -Female-Specific Criteria:

  18. Negative beta-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment if woman is presumed to be of reproductive potential.
  19. Agrees to use an effective means of birth control from at least 21 days prior to enrollment through 24 weeks after last study vaccination if presumed to be of reproductive potential.

EXCLUSION CRITERIA:

Exclusion Criteria for Groups 1, 2, and 3

A volunteer will be excluded if one or more of the following conditions apply:

Volunteer has received any of the following substances:

  1. Investigational Marburg vaccine in a prior clinical trial.
  2. Investigational Ebola vaccine in a prior clinical trial.
  3. Investigational cAd3 or MVA vaccines in a prior clinical trial.
  4. Evidence of increased cardiovascular disease risk defined as >10% five year risk by the non-laboratory method.
  5. 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.
  6. Type 1 hypersensitivity reaction to aminoglycoside antibiotics.
  7. 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.
  8. Blood products within 112 days (16 weeks) prior to enrollment.
  9. Investigational research agents within 28 days (4 weeks) prior to enrollment.
  10. Live attenuated vaccines within 28 days (4 weeks) prior to enrollment.
  11. 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
  12. Current anti-tuberculosis prophylaxis or therapy.

    -Female-specific criteria:

  13. Woman who is breast-feeding or planning to become pregnant during the 24 weeks of study participation.

    -Volunteer has a history of any of the following clinically significant conditions:

  14. Serious adverse reactions to vaccines such as anaphylaxis, urticaria (hives), respiratory difficulty, angioedema, or abdominal pain.
  15. Clinically significant autoimmune disease or immunodeficiency.
  16. Asthma that is not well controlled.
  17. Diabetes mellitus (type I or II), with the exception of gestational diabetes.
  18. Thyroid disease that is not well controlled.
  19. A history of hereditary angioedema (HAE), acquired angioedema (AAE), or idiopathic forms of angioedema.
  20. Idiopathic urticaria within the last 1 year.
  21. Hypertension that is not well controlled.
  22. Bleeding disorder diagnosed by a doctor (e.g. factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws.
  23. Malignancy that is active or history of a malignancy that is likely to recur during the period of the study.
  24. Seizure in the past 3 years or treatment for seizure disorder in the past 3 years.
  25. Asplenia or functional asplenia.
  26. Psychiatric condition that precludes compliance with the protocol; past or present psychoses; or within five years prior to enrollment, history of a suicide plan or attempt.
  27. Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a volunteer s ability to give informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02408913


Locations
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United States, Georgia
Hope Clinic - Emory Vaccine Ctr
Decatur, Georgia, United States, 30030
United States, Maryland
University of Maryland, Baltimore
Baltimore, Maryland, United States, 21201-1595
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Julie E Ledgerwood, D.O. National Institute of Allergy and Infectious Diseases (NIAID)
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT02408913    
Other Study ID Numbers: 150107
15-I-0107
First Posted: April 6, 2015    Key Record Dates
Last Update Posted: April 11, 2019
Last Verified: April 6, 2017
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
Immunity
Ebola Virus
Ebola Hemorrhagic Fever
Healthy
Filovirus
Additional relevant MeSH terms:
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Vaccinia
Virus Diseases
Poxviridae Infections
DNA Virus Infections