Clinical trial NCT03583606: A Trial to Evaluate the Safety and Systems Biology Response of Ebolavirus Zaire Vaccine (ChAd3-EBO-Z)
Official title: A Systems Biology Phase 1 Evaluation of the Safety, Reactogenicity, and Immunogenicity of Chimpanzee Adenovirus Type 3- Vectored Zaire Ebolavirus (ChAd3-EBO-Z) and Modified Vaccinia Ankara- Vectored Multivalent Filovirus (MVA-BN(R)-Filo) Vaccine Candidates
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ebola Disease
Immunisation
Keywords: Adenovirus vector
Ebola Virus
Immunogenicity
Non-Human Primates Vaccination/Challenge Studies
Phase 1
Reactogenicity
Safety
Zaire ebolavirus vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
First posted: 2018-07-11
Enrollment: 61
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed description: This is a Phase 1, randomized, double-blind trial of 60 evaluable males and non-pregnant females, 18-45 years old, inclusive, who are in good health, meet all eligibility criteria, and do not meet any exclusion criteria. This trial is designed to assess the safety, reactogenicity and immunogenicity of an Ebolavirus Zaire (ChAd3-EBO-Z) vaccine for the prevention of Ebola. ChAd3-EBO-Z will be administered intramuscularly into the deltoid of all participants on Day 1. On Day 8, subjects will receive either placebo, ChAd3-EBO-Z , or MVA- BN(R)-Filo boosters, administered intramuscularly into the deltoid of the arm opposite their first vaccination, based on study group. There will be 20 subjects in each group. Subjects will be monitored for 6 months after vaccination to assess safety and efficacy for ChA3d-EBO-Z with homologous and heterologous boosting. Differences between the homologous and heterologous arm represent potential points for further, more in depth assessment to determine if there is a correlation with efficacy. Long term goals include comparing results from this study with results from naturally infected individuals as well as non-human primate (NHP) vaccination/challenge studies. 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. The secondary study objective is to assess the antibody response to Zaire ebolavirus (EBOV) glycoprotein (GP) by study group.

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.

Primary outcomes:
measure: Number of Participants With Clinical Safety Laboratory Adverse Events
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants Reporting Serious Adverse Events (SAEs)
timeFrame: Day 1 to Day 182
measure: Number of Participants Reporting Solicited Local Reactogenicity
timeFrame: Day 1 to Day 8 Post First Vaccination
measure: Number of Participants Reporting Solicited Local Reactogenicity
timeFrame: Day 1 to Day 8 Post Second Vaccination
measure: Number of Participants Reporting Solicited Local Reactogenicity
timeFrame: Day 1 to Day 15
measure: Number of Participants Reporting Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 8 Post First Vaccination
measure: Number of Participants Reporting Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 8 Post Second Vaccination
measure: Number of Participants Reporting Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 15
measure: Number of Participants Reporting Vaccine-related Medically Attended Adverse Events (MAAEs)
timeFrame: Day 1 to Day 182
measure: Number of Participants Reporting Vaccine-related Unsolicited Adverse Events (AEs)
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - White Blood Cells
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Hemoglobin
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Platelet Count
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Absolute Neutrophil Count
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - ALT
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Creatinine (Increase)
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Sodium
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - Potassium
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Clinical Safety Laboratory Adverse Events - BUN
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
measure: Number of Participants by Severity of Solicited Local Reactogenicity
timeFrame: Day 1 to Day 8 Post First Vaccination
measure: Number of Participants by Severity of Solicited Local Reactogenicity
timeFrame: Day 1 to Day 8 Post Second Vaccination
measure: Number of Participants by Severity of Solicited Local Reactogenicity
timeFrame: Day 1 to Day 15
measure: Number of Participants by Severity of Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 8 Post First Vaccination
measure: Number of Participants by Severity of Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 8 Post Second Vaccination
measure: Number of Participants by Severity of Solicited Systemic Reactogenicity
timeFrame: Day 1 to Day 15
measure: Number of Participants by Severity of Vaccine-related Unsolicited Adverse Events (AEs)
timeFrame: Day 1 to approximately 28 Days Post Second Vaccination
Secondary outcomes:
measure: Geometric Mean Fold Rise (GMFR) as Measured by Anti-EBOV GP ELISA - ITT Population
timeFrame: Day 8, 15, 22, 29 and 36 compared to baseline (Day 1) reported as Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
measure: Geometric Mean Fold Rise (GMFR) as Measured by Anti-EBOV GP ELISA - Per Prototocol Population
timeFrame: Day 8, 15, 22, 29 and 36 compared to baseline (Day 1) reported as Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
measure: Geometric Mean Titer (GMT) as Measured by Anti-EBOV GP ELISA - ITT Population
timeFrame: Day 1, 8, 15, 22, 29 and 36 reported as Day 1 first vaccination, Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
measure: Geometric Mean Titer (GMT) as Measured by Anti-EBOV GP ELISA - Per Protocol Population
timeFrame: Day 1, 8, 15, 22, 29 and 36 reported as Day 1 first vaccination, Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
measure: Seroconversion as Measured by Anti-EBOV GP ELISA - ITT Population
timeFrame: Day 8, 15, 22, 29 and 36 reported as Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
measure: Seroconversion as Measured by Anti-EBOV GP ELISA - Per Protocol Population
timeFrame: Day 8, 15, 22, 29 and 36 reported as Day 8 post-first vaccination, Day 8 post-second vaccination, Day 15 post-second vaccination, Day 22 post-second vaccination, and Day 29 post-second vaccination, respectively.
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center Vaccine Research Center
state: Ohio
Study officials:
References: