Dosage-Escalation Study of the Safety and Immunogenicity of a Novel Rabies Vaccine ChAd155-RG vs. the Comparator RABAVERT Vaccine in Healthy Adult Subjects

Exclusion Criteria

• •1. Was ever vaccinated with a licensed or investigational rabies vaccine\* or was diagnosed with rabies exposure, infection, or disease.
• •\*Includes RABAVERT and Imovax. Subject's verbal history will suffice.
• •2. Has a higher risk than the average US resident with regard to exposure to rabies, per the Rabavert package insert and rabies vaccination recommendations from the CDC\*.
• •* People at high risk of exposure to rabies, such as veterinarians, animal handlers, rabies laboratory workers, spelunkers, and rabies biologics production workers.
• •* People whose activities bring them into frequent contact with rabies virus or with possibly rabid animals.
• •* International travelers who are likely to come in contact with animals in parts of the world where rabies is common.
• •3. Was ever vaccinated with a licensed or investigational Ad vector or Ad vaccine.
• •4. Is currently taking chloroquine or hydroxychloroquine.
• •5. Was diagnosed with laboratory-confirmed COVID-19 (PCR or antigen-based test) in the preceding 28 days.
• •6. Positive serology for HIV antibody, HCV antibody, or Hepatitis B surface antigen (HBsAg).
• •7. Has known allergy or history of anaphylaxis or other serious adverse reaction to a vaccine or vaccine products\*.
• •\*Including egg products, aminoglycosides, gelatin, sorbitol, tris (hydroxymethyl)-amino methane (THAM), or any of the constituents of the study vaccines.
• •8. Has severe allergy or anaphylaxis to latex.
• •9. Has an acute illness or temperature = / \>38.0 Degrees Celsius on Day 1\*.
• •\*Subjects with fever or acute illness on the day of vaccination may be re-assessed and enrolled if healthy or only minor residual symptoms remain within 3 days.
• •10. Female subjects who are pregnant or breastfeeding, or planning to become pregnant while enrolled in this trial and at least 60 days after last vaccination.
• •11. Has history of autoimmune disease, or clinically significant cardiac, pulmonary, hepatic, rheumatologic, or renal disease by history, physical examination, and/or lab studies.
• •12. Has history of malignancy other than squamous cell or basal cell skin cancer, unless there has been surgical excision that is considered to have achieved cure\*.
• •\*Subjects with a history of skin cancer must not be vaccinated at the previous tumor site.
• •13. Has known or suspected congenital or acquired immunodeficiency, or recent history or current use of immunosuppressive therapy\*.
• •\*Anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term (= / \>2 weeks within the previous 3 months) systemic corticosteroid therapy (at a dosage of = / \>0.5 mg/kg/day). Intranasal or topical prednisone (or equivalent) are allowed.
• •14. Is post-organ and/or stem cell transplant, whether or not on chronic immunosuppressive therapy.
• •15. Had major surgery (per the investigator's judgment) within 4 weeks before study entry or planned major surgery during this trial.
• •16. Has history of diabetes mellitus type 1 or type 2, including cases controlled with diet alone.
• •\*Note: history of isolated gestational diabetes is not an exclusion criterion.
• •17. Has history of thyroidectomy, or thyroid disease requiring medication in the last 12 months.
• •18. Has history of hypertension, even if medically controlled.
• •\*Note: Vital signs must be normal by protocol toxicity grading scale. In the event of an abnormal heart rate or blood pressure due to physiological variation or activity, the subject may rest for 10 minutes in a quiet room, and then blood pressure and/or heart rate re-measured. Repeated vital signs may be used to determine eligibility.
• •19. Received live attenuated vaccines from 30 days before first vaccination until 30 days after final vaccination\*.
• •\*Not including licensed or authorized COVID-19 vaccines.
• •20. Received killed or inactivated vaccines from 14 days before first vaccination until 30 days after final vaccination\*.
• •\*Not including licensed COVID-19 vaccines
• •21. Received experimental therapeutic agents within 3 months before first vaccination or plans to receive any experimental therapeutic agents during this trial\*.
• •\*That that in the opinion of the investigator would interfere with safety or immunogenicity assessments.
• •22. Is currently participating or plans to participate in another clinical study which would involve receipt of the following:\*
• •\* An investigational product, blood drawing, or an invasive medical procedure that would require administration of anesthetics, intravenous (IV) dyes, or removal of tissue during this trial and, in the opinion of the investigator, would interfere with safety or immunogenicity assessments.
• •-Includes endoscopy, bronchoscopy, and administration of IV contrast.
• •23. Received blood products or immunoglobulin in the 3 months before study entry or planned use during this trial.
• •24. Donated a unit of blood or blood products within 8 weeks before Day 1 or plans to donate blood or blood products during this trial.
• •25. Has major psychiatric illness in the past 12 months that in the opinion of the investigator would preclude participation.
• •26. Has current alcohol use or current or past abuse of recreational or narcotic drugs by history as judged by the investigator to potentially interfere with study adherence.
• •27. Has a history of chronic urticaria.
• •28. Has tattoos, scars, or other marks on both deltoid areas which would, in the opinion of the investigator, interfere with assessment of the vaccination site.
• •29. Is a site employee\* or staff who are paid entirely or partially by/through the OCRR contract for this trial, or staff who are supervised by the Principal Investigator (PI) or sub-investigators.
• •\*Including the PI, sub-investigators listed on Form FDA 1572 or Investigator of Record Form.
• •30. In the opinion of the investigator cannot communicate reliably, is unlikely to adhere to the requirements of this trial, or has any condition which would limit the ability to complete this trial.
• •31. Has history of Guillain-Barre syndrome, meningitis, encephalitis, neuroparalysis, transient paralysis, myelitis, retrobulbar neuritis, multiple sclerosis, vertigo, or visual disturbances.
• •32. Has a history of arterial or venous thrombosis, or thrombocytopenia that required medical attention.