ADVP005; Dengue CVD 12000 - Dengue-1-Virus Live Virus Human Challenge (DENV-1-LVHC)

This is an interventional basic science trial for Dengue Read More

Inclusion Criteria:

• 1. Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent.
• 2. Tetravalent dengue antibody response at 28 days following final vaccination for vaccinated groups of volunteers.
• 3. Volunteers must be able and willing to provide written informed consent.
• 4. Volunteers must be healthy as established by medical history and clinical examination at study entry.
• 5. Volunteers must pass a comprehension test and be able to comply with all study requirements.
• 6. Female volunteers of non-childbearing potential (non-childbearing potential is defined as having had one of the following: a tubal ligation at least 3 months prior to enrollment, a hysterectomy, an oophorectomy, or is post-menopausal).
• 7. Female volunteers of childbearing potential may be enrolled in the study, if all of the following apply:
• Practiced adequate contraception (see Definition of Terms, section 5.4.2.3.) for 30 days prior to challenge
• Has a negative urine pregnancy test on the day of DHIM
• Agrees to continue adequate contraception until two months after completion of the DHIM
• 8. Provide consent for release of medical history records from primary care physician, college or university medical center, urgent care, or emergency room visit

Exclusion Criteria:

• 1. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
• 2. Recent (in the past 4 weeks) travel to any dengue endemic area. These potential volunteers may be eligible for enrollment a minimum of 4 weeks later
• 3. Volunteer seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
• 4. Unvaccinated volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus.
• 5. Any history of FV infection or FV vaccination except for participation in the ADVP003 or ADVP004 dengue vaccination studies; during the study period (Note: Late time point serology from the trials can be tested concomitant to screening serology to clarify if incident FV infection has occurred between vaccination and challenge)
• 6. Medical history of, or current, diabetes, chronic obstructive pulmonary disease, peptic ulcer disease, coronary artery disease, cardiac arrhythmia, cardiomyopathy, pericarditis, or auto-immune disease
• 7. Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months)
• 8. History of Guillain-Barré syndrome (GBS)
• 9. History of bipolar disorder, schizophrenia, hospitalization in the past year for a mental health disorder, or any other psychiatric condition, which in the opinion of the investigator prevents the volunteer from participating in the study
• 10. Safety laboratory test results at screening that are deemed clinically significant or more than Grade 1 deviation from normal with the exception of PT/PTT, fibrinogen decrease, ALT/AST increase (<1.1 x ULN acceptable), platelet decrease which will be exclusionary at Grade 1 or higher
• 11. Significant screening physical examination abnormalities at the discretion of the investigator, including a BMI > 35 kg/m2
• 12. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months)
• 13. Female: pregnant, lactating or history of heavy menstrual bleeding menstrual periods lasting consistently and regularly longer than 6 days, or consistently and regularly requiring 5 or more pads or tampons per day, and volunteer to the opinion and review of the investigator.
• 14. Female volunteers using an intrauterine device (IUD) or Mirena®
• 15. Female volunteers with a history of clinically significant fibroids or uterine polyps, endometriosis, dysmenorrhea, adenomyosis, and uterine scarring (e.g. after D&C), unless treated, with no active clinically significant disease
• 16. Allergy (hives, shortness of breath, swelling of the lips or throat), or hospitalization related to a previous vaccination, anaphylaxis of unknown etiology, or allergy to specific medications/animals for which antigens may be in the virus preparations to include: Shellfish allergy, Fetal Bovine Serum, L-Glutamine, Neomycin and Streptomycin
• 17. Recent blood donation within prior 56 days of inoculation or planning to donate blood in the one 1 year following inoculation with dengue virus
• 18. Receipt of blood products or antibodies within 90 days of inoculation or during the study period
• 19. Any personal beliefs that bar the administration of blood products, transfusions, or serum albumin
• 20. Participation in the 4 weeks preceding inoculation, or planned participation during the present trial period, in another clinical trial investigating a vaccine except for participation in the ADVP003 or ADVP004 study, drug, medical device, or medical procedure
• 21. Planned administration of a licensed or study vaccine not planned in the study protocol during the period starting 30 days prior to the DHIM for a live vaccine or 14 days prior to DHIM for inactivated vaccines and extending until 56 days after study completion
• 22. Planned or current administration of an HMG-CoA reductase inhibitor (i.e., lovastatin, simvastatin, atorvastatin, etc.)
• 23. Currently taking methadone or suboxone
• 24. Currently regularly taking anti-coagulant medication, aspirin or non-steroidal anti-inflammatory drugs (NSAIDs)
• 25. Chronic migraine headaches, defined as more than 15 headache days per month over a 3-month period of which more than 8 are migraines, in the absence of medication over use
• 26. Chronic or recent acute medical condition that, in the opinion of the investigator, impacts volunteer safety.