Dengue 4 Human Infection Model (Dengue CVD 11000; DHIM-4)

This is an interventional basic science trial for Dengue Read More

Inclusion Criteria:

• Male or non-pregnant, non-breastfeeding female between 18 and 50 years of age (inclusive) at the time of consent
• Volunteers must be able to provide written informed consent.
• Volunteers must be healthy as established by medical history and clinical examination at study entry
• Volunteers must pass a comprehension test and be able to comply with all study requirements.
• 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 ovariectomy, or is post-menopausal).
• Female volunteers of childbearing potential may be enrolled in the study, if all the following apply:
• Practiced adequate contraception 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

Exclusion Criteria:

• History of dengue infection or dengue illness, or history of flavivirus infection or vaccination (e.g., yellow fever, tick-borne-encephalitis virus [TBEV], Japanese encephalitis, and dengue)
• Volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus.
• Planned administration of any flavivirus vaccine for the entire study duration
• Any recent (within 4 weeks) or planned travel to any dengue endemic area while participating in the trial
• Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination (no laboratory testing required)
• Volunteer seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
• 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 (acceptable to 1.1 ULN), platelet decrease which will be exclusionary at Grade 1 or higher
• Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic or renal functional abnormality, as determined by physical examination or laboratory screening tests
• 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
• Significant screening physical examination abnormalities at the discretion of the investigator, including a BMI > 35 kg/m2
• Planned administration or administration of a vaccine/product not planned in the study protocol during the period starting 30 days prior to the DHIM until 56 days after the study completion (routine influenza or COVID-19 vaccination will be allowed if it is not administered within 14 days preceding DHIM)
• Use of any investigational or non-registered product (drug or vaccine) other than the study DHIM during the period starting 30 days preceding the DHIM and/or planned use during the study period
• Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs during the period starting 90 days prior to the DHIM (for corticosteroids, this will mean prednisone 5 mg/day or equivalent; inhaled, intranasal and topical steroids are allowed)
• Concurrently participating in another clinical study, at any time during the study period, in which the volunteer has been or will be exposed to an investigational or a noninvestigational product (pharmaceutical product or device)
• Autoimmune disease or history of autoimmune disease
• History of any reaction or hypersensitivity likely to be exacerbated by any component of the study product or related to a study procedure
• Major congenital defects or serious chronic illness
• History of any neurological disorders or seizures
• Acute disease and/or fever (≥37.5°C/99.5°F oral body temperature) at the time of enrollment: note that a volunteer with a minor illness such as mild diarrhea, mild upper respiratory infection, etc., without fever, may be enrolled at the discretion of the investigator
• Administration of immunoglobulins and/or any blood products during the period starting 90 days preceding the DHIM or planned administration during the study period
• Recent history of chronic alcohol consumption (more than 2 drinks per day and/or drug abuse) based on volunteer reported history
• Pregnant or breastfeeding female or female currently planning to become pregnant or planning to discontinue adequate contraception
• Men who intend to father a child during the study period (approximately 2 months)
• Any religious or personal beliefs that bar the administration of blood products, transfusions or serum albumin
• Planned or current administration of an HMG-CoA reductase inhibitor (i.e., lovastatin, simvastatin, atorvastatin, etc.)
• Currently regularly taking anti-coagulant medication, aspirin, or non-steroidal anti-inflammatory drugs (NSAIDs)
• Any other condition which, in the opinion of the investigator, prevents the volunteer from participating in the study
• Temporary Exclusion Criteria:
• Acute disease and/or fever (> 38°C/100.4°F oral body temperature) at the time or within 6 hours of challenge inoculation: note that a volunteer with a minor illness such as mild upper respiratory infection, etc., without fever, and with a negative SARS-CoV-2 upper respiratory (NP or nasal) swab PCR on the day of inoculation, may be enrolled at the discretion of the investigator.
• Recent blood donation (within prior 56 days).
• Recent or scheduled receipt of any live vaccine 30 days and/or inactivated or sub-unit vaccine 14 days prior to inoculation.
• Safety labs may be repeated once. If outside the 90-day screening window, the volunteer may be rescreened except for flavivirus, hepatitis, and HIV viral screens.