A Trial to Evaluate the Safety and Systems Biology Response of Ebolavirus Zaire Vaccine (ChAd3-EBO-Z)
Condition: Ebola Disease; Immunisation
MeSH terms: Hemorrhagic Fever, Ebola
Intervention: ChAd3-EBO-Z; MVA Multi-Filo Ebola Vaccine; Placebo
Intervention description: Zaire ebolavirus vaccine administered by an IM injection into the deltoid as a single dose of 2 x 10^11 virus particles (vp)).; A booster vaccination of replication defective MVA-BN-Filo administered by an IM injection into the deltoid as a single dose of 1 x 10^8 Infectious Units (IU).; 0.5 mL normal saline administered via IM injection into the deltoid.
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 61.0
Sex: All
Minimum age: 18 Years
Maximum age: 45 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Adenovirus vector; Ebola Virus; Immunogenicity; Non-Human Primates Vaccination/Challenge Studies; Phase 1; Reactogenicity; Safety; Zaire ebolavirus vaccine

Summary:

      This initial, proof of concept study will focus on identifying significant differences in
      response to the Ebolavirus Zaire vaccine (ChAd3-EBO-Z) when administered with placebo,
      MVA-BN(R)-Filo, or ChAd3-EBO-Z boosters after 8 days. All 60 participants will receive the
      ChAd3-EBO-Z vaccine and then randomized into each booster group (20 receiving each type of
      booster). Subjects will be followed-up for 6 months to monitor for safety outcomes and
      efficacy measures. There is no formal hypothesis for this study. The primary objective of
      this study is to assess the safety and reactogenicity of study products by study group when
      administered IM to healthy adults.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Provide written informed consent before initiation of any study procedures.

          2. Are able to understand and comply with planned study procedures and be available for
             all study visits/phone calls.

          3. Males or non-pregnant females ages 18-45, inclusive.

          4. Subject must have a body mass index (BMI) > / = 18.5 and < 35 kg/m^2.

          5. Are in good health.

               -  As determined by medical history and physical examination to evaluate acute or
                  currently ongoing chronic medical diagnoses or conditions, defined as those that
                  have been present for at least 90 days which would affect the assessment of the
                  safety of subjects or the immunogenicity of study vaccinations. Chronic medical
                  diagnoses or conditions should be stable for the last 60 days (no
                  hospitalizations, ER or urgent care for condition and no adverse symptoms that
                  need medical intervention such as medication change/supplemental oxygen). This
                  includes no change in chronic prescription medication, dose, or frequency as a
                  result of deterioration of the chronic medical diagnosis or condition in the 60
                  days prior to enrollment. Any prescription change that is due to change of health
                  care provider, insurance company, etc., or that is done for financial reasons, as
                  long as in the same class of medication, will not be considered a deviation of
                  this inclusion criterion. Any change in prescription medication due to
                  improvement of a disease outcome, as determined by the site principal
                  investigator or appropriate sub-investigator, will not be considered a deviation
                  of this inclusion criterion. Subjects may be on chronic or as needed (prn)
                  medications if, in the opinion of the site principal investigator or appropriate
                  sub-investigator, they pose no additional risk to subject safety or assessment of
                  reactogenicity and immunogenicity and do not indicate a worsening of medical
                  diagnosis or condition. Similarly, medication changes subsequent to enrollment
                  and study vaccination are acceptable provided there was no deterioration in the
                  subject's chronic medical condition that necessitated a medication change, and
                  there is no additional risk to the subject or interference with the evaluation of
                  responses to study vaccination. Note: Topical, nasal, and inhaled medications
                  (apart from steroids as outlined in the Subject Exclusion Criteria), herbals,
                  vitamins, and supplements are permitted.

          6. Oral temperature is less than 100.0 degrees Fahrenheit (37.8 degrees Celsius).

          7. Pulse is 47 to 105 beats per minute (bpm), inclusive.

          8. Systolic blood pressure (BP) is 85 to 150 mm Hg, inclusive.

          9. Diastolic blood pressure (BP) is 55 to 95 mm Hg, inclusive.

         10. Have acceptable screening laboratories within 28 days prior to enrollment

               -  Screening labs include white blood cell (WBC), Hgb, platelet count, ANC, sodium,
                  potassium, creatinine, albumin, total protein, PT, PTT, alanine aminotransferase
                  (ALT). Blood Urea Nitrogen (BUN) will be obtained only if creatinine is above
                  normal range.

                    -  Screening laboratory values that are outside the range of eligibility but
                       are thought to be due to an acute condition or due to laboratory error may
                       be repeated once.

         11. Have normal screening laboratories for urine protein. Trace protein is acceptable.

         12. Drug screen for opiates is negative.

         13. Hemoglobin A1C (HgbA1C) < 6.3% at screening.

         14. HIV 1/2 antibody negative.

         15. HCV antibody negative.

         16. HBsAg negative.

         17. Women of childbearing potential, must be using an effective method of contraception
             from 30 days prior to the first study vaccination until 90 days after the second study
             vaccination.

             - Women of childbearing potential are not sterilized via tubal ligation, bilateral
             oophorectomy, hysterectomy, successful Essure(R) placement (permanent, non-surgical,
             non-hormonal sterilization) with history of documented radiological confirmation test
             at least 90 days after the procedure (or with use of another birth control method if
             history of confirmation test not confirmed), still menstruating, or < 1 year of the
             last menses if menopausal.

             -- Effective methods of contraception includes, but is not limited to, non-male sexual
             relationships, abstinence from sexual intercourse with a male partner, monogamous
             relationship with a vasectomized partner, male condoms with the use of applied
             spermicide, intrauterine devices, NuvaRing(R), and licensed hormonal methods such as
             implants, injectables or oral contraceptives ("the pill").

         18. Women of childbearing potential must have a negative serum pregnancy test at screening
             and a negative urine pregnancy test within 24 hours prior to each study vaccination.

         19. Women agree to not donate eggs (ova, oocytes) from the start of screening onwards
             until at least 90 days after the second vaccination.

         20. Agrees not to participate in another clinical trial during the study period.

         21. Agrees not to donate blood to a blood bank for 3 months after receiving the second
             study vaccine.

        Exclusion Criteria:

          1. Women who are pregnant, planning to become pregnant or lactating. - Includes
             breastfeeding or planning to breastfeed at any given time from the receipt of study
             vaccination through the 6-month trial period.

          2. Known allergy or history of anaphylaxis, severe local or other serious adverse
             reactions to vaccines or vaccine products, or history of severe allergic reactions.

             - Includes a known allergy to egg, egg products and aminoglycosides or any of the
             constituents of the study vaccines [e.g., polysorbate 80, ethylenediaminetetraacetic
             acid (EDTA), L-histidine, tris (hydroxymethyl)-amino methane (THAM)).

          3. Received an experimental agent within 3 months prior to Day 1, or expects to receive
             an experimental agent (other than from participation in this study) during the 6-month
             trial-reporting period.

             - Including vaccine, drug, biologic, device, blood product, or medication.

          4. Received immunoglobulin or other blood product within 3 months before enrollment in
             this study.

          5. Received any licensed live vaccine within 30 days prior to the first study vaccination
             through 30 days after the second study vaccination.

          6. Received a licensed inactivated vaccine within 14 days prior to the first study
             vaccination through 14 days after the second study vaccination.

          7. Has been vaccinated with an Ebola vaccine.

          8. Has been diagnosed with Ebola disease, or exposed to Ebola virus including travel to
             West Africa in 2014-2016.

             - West Africa includes but is not limited to the countries of Guinea, Liberia, Mali,
             Nigeria, and Sierra Leone.

          9. Known or suspected receipt of ChAd3-EBO-Z or other ChAd3-vectored vaccine.

         10. Known or suspected receipt of an adenovirus serotype 5 (Ad5)-based vaccine.

         11. Known or suspected receipt of any licensed or investigational small pox
             (vaccinia)-based vaccine.

             - Includes any MVA-based candidate vaccine (Imvamune or Imvanex), Dryvax, or Acam2000.

         12. Has a typical vaccinia scar.

         13. Confirmed Asplenia/Functional Asplenia.

         14. A history of bleeding or clotting disorders.

         15. Thyroidectomy or thyroid disease requiring medication during the last 12 months.

         16. History of chronic urticaria (recurrent hives).

         17. Individuals in whom the ability to observe possible local reactions at the eligible
             injection sites (left and right deltoid region) is, unacceptably obscured due to a
             physical condition or permanent body art.

         18. Have an acute illness, as determined by the site PI or appropriate sub-investigator,
             within 72 hours prior to study vaccination.

             - An acute illness which is nearly resolved with only minor residual symptoms
             remaining is allowable if, in the opinion of the site PI or appropriate
             sub-investigator, the residual symptoms will not interfere with the ability to assess
             safety parameters as required by the protocol. Subjects may re-screen after an acute
             illness is resolved.

         19. Any confirmed or suspected immunosuppressive or immunodeficient condition (including
             HIV infection) or use of anticancer chemotherapy or radiation therapy (cytotoxic)
             within 3 years prior to study vaccination

         20. Administration of chronic (defined as more than 14 days) immunosuppressants or other
             immune modifying drugs within 6 months of receipt of study vaccine.

         21. Have taken oral or parenteral (including intraarticular) corticosteroids of any dose
             within 30 days prior to study vaccination.

         22. Have taken high-dose dose inhaled corticosteroids within 30 days prior to study
             vaccination.

             - High-dose defined using the inhaled high-dose reference chart.

         23. Have a history of convulsions or encephalomyelitis within 90 days prior to study
             vaccination.

         24. Current or past history of alcohol or drug abuse in the last 5 years.

         25. Subjects with autoimmune disorders, chronic inflammatory disorders or neurological
             disorders with a potential autoimmune correlation.

         26. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
             psychiatric diagnosis that may interfere with subject compliance or safety
             evaluations.

         27. Have been hospitalized for psychiatric illness, history of suicide attempt, or
             confinement for danger to self or others within 10 years prior to study vaccination.

         28. Have received any antiviral within 3 days of study vaccination

         29. History of myocarditis, pericarditis, cardiomyopathy, transient ischemic attack or
             stroke, myocardial infarction, angina, coronary artery disease, congestive heart
             failure, clinically significant arrhythmia.

             - Including any arrhythmia requiring medication, treatment, or clinical follow-up.

         30. Electrocardiogram (ECG) with clinically significant findings.

             - Clinically significant findings include the following:

               -  Conduction disturbance (complete left or complete right bundle branch block or
                  nonspecific intraventricular conduction disturbance with QRS = / > 120 ms, PR
                  interval = / > 210 ms, any second- or third-degree atrioventricular block, or
                  prolongation of the QT interval corrected according to Bazett's formula [QTcB] [>
                  450 ms]).

               -  Significant repolarization (ST-segment or T-wave) abnormality.

               -  Significant atrial or ventricular arrhythmia; frequent atrial or ventricular
                  ectopy (e.g., frequent premature atrial contractions, 2 premature ventricular
                  contractions in a row).

               -  ST-elevation consistent with ischemia or evidence of past or evolving myocardial
                  infarction

         31. A diagnosis of Type I or II diabetes. (A history of isolated gestational diabetes is
             not an exclusion criterion).

         32. Current employee or staff paid entirely or partially by the contract for this trial,
             or staff who are supervised by the PI or Sub-Investigators.

         33. Any condition that would, in the opinion of the Site Investigator or appropriate
             sub-investigator, is a contraindication to study participation.

               -  Including acute or chronic (persisting for at least 90 days) clinically
                  significant medical disease or condition, that would place the subject at an
                  unacceptable risk of injury, render the subject unable to meet the requirements
                  of the protocol, or may interfere with the evaluation of responses or the
                  subject's successful completion of the study.