Clinical trial NCT05268302: Dengue 4 Human Infection Model (Dengue CVD 11000; DHIM-4)
Official title: Phase One, Open Label, Assessment of a Dengue-4-Virus-Live Virus Human Challenge - (DENV-4-LVHC) Virus Strain in Healthy U.S. Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Dengue
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: Medical Technology Enterprise Consortium (MTEC)
First posted: 2022-03-07
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this research study is to test a weakened form of an experimental dengue virus challenge at different doses to test if participants develop symptoms or circulating virus in the blood (called viremia). When volunteers are exposed to dengue on purpose, it is called a "challenge" or Dengue Human Infection Model (DHIM). The research team is collecting information about the safety of the challenge and the best dose to use. The information may help us to make a dengue challenge (a DHIM) that will test vaccines to protect people from dengue.

Detailed description: The purpose of this research study is to test a weakened form of an experimental dengue virus challenge at different doses to test if participants develop symptoms or circulating virus in the blood (called viremia). When volunteers are exposed to dengue on purpose, it is called a "challenge" or Dengue Human Infection Model (DHIM). The research team is collecting information about the safety of the challenge and the best dose to use. The information may help the research team to make a dengue challenge (a DHIM) that will test vaccines to protect people from dengue. The duration of participation will last for 180 days (six months) after challenge including up to 22 visits. After participants are exposed to the weakened dengue virus, the research team will follow them closely to measure their symptoms. Like the flu, participants might expect to have a headache, rash, body aches, fever and chills or they may experience no symptoms whatsoever. If participants do develop symptoms, the research team will monitor them closely in a local hotel or a wing of our hospital to ensure safety and to treat symptoms if they occur.

Eligibility criteria: 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) (Note: for the homologous rechallenge sub-study, criteria does not apply)
* Volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus. (Note: for the homologous rechallenge sub-study, criteria does not apply)
* 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.

Primary outcomes:
measure: Number of Participants With Solicited Injection Site Adverse Events
timeFrame: Days 1-7 post-challenge
measure: Number of Participants With Unsolicited Injection Site Adverse Events
timeFrame: Days 2, 4-16, 28
measure: Number of Participants With Solicited Systemic Adverse Events
timeFrame: Days 2, 4-16, 28
measure: Incidence of Abnormal Laboratory Measurements
timeFrame: Days 2, 4-16, 28
measure: Number of Participants With Dengue-Related Adverse Events
timeFrame: Days 2, 4-16, 28
measure: Number of Participants With Unsolicited Systemic Adverse Events
timeFrame: Days 2, 4-16, 28
measure: Number of Participants With Short-Term SAEs
timeFrame: Days 2, 4-16, 28
measure: Number of Participants With Long-Term SAEs
timeFrame: Days 2, 4-16, 28, 180
measure: Number of Participants With Fever
timeFrame: Days 2, 4-16, 28, 180
Secondary outcomes:
measure: Number of Participants With Detected Viremia
timeFrame: Days 2, 4-16, 28
measure: Microneutrilization (50%) Geometric Mean Titer
timeFrame: Day 28
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland, Baltimore, Center for Vaccine Development and Global Health
state: Maryland
Study officials:
References: