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DenguePhase 1NCT05268302

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

A Phase 1 study testing Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose and Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge in people with Dengue, run by University of Maryland, Baltimore at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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). Read more about this study

Who is it for?
Ages 18 to 50 yearsHealthy volunteers can take part
Conditions the study is for
Dengue
What is being tested?
Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose and Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
1 siteUnited States
Study dates
28 Feb 2022to 4 Jan 2024
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 50 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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:
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  • 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

Who cannot join

  • 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)
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  • 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.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • University of Maryland, Baltimore, Center for Vaccine Development and Global Health

    Baltimore, Maryland, 21201

Other trials in United States

About this study

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

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.

Read the 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.

Conditions
Dengue
Being tested
Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose, Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge
Medical subject headings
Dengue

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low DoseBiological

    Low dose 0.5 mL of the challenge strain is administered subcutaneously in the triceps region of the arm on Study Day 0.

  • Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous RechallengeBiological

    Also called Homologous Rechallenge

    Low dose 0.5 mL of the challenge strain is administered subcutaneously in the triceps region of the arm on Study Day 366 in previously dosed participants.

Study groups in NCT05268302
Study groupRoleWhat they receive
Low Dose Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - PrimaryExperimental0.95 x 10^2 Plaque Forming Units
Receives: Biological: Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose
Low Dose Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Homologous RechallengeExperimental0.95 x 10^2 Plaque Forming Units
Receives: Biological: Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With Solicited Injection Site Adverse Events

    solicited injection site adverse events until 7 days post virus inoculation

    Measured: Days 1-7 post-challenge

  2. Number of Participants With Unsolicited Injection Site Adverse Events

    unsolicited injection site adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 28

  3. Number of Participants With Solicited Systemic Adverse Events

    solicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 28

  4. Incidence of Abnormal Laboratory Measurements

    Incidence of abnormal laboratory measurements until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 28

  5. Number of Participants With Dengue-Related Adverse Events

    dengue-related like adverse events until 28 days post virus inoculation or 7 days post inpatient whichever is later

    Measured: Days 2, 4-16, 28

  6. Number of Participants With Unsolicited Systemic Adverse Events

    unsolicited systemic adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 28

  7. Number of Participants With Short-Term SAEs

    Number of SAEs until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 28

  8. Number of Participants With Long-Term SAEs

    Number of SAEs until 6 months post virus inoculation

    Measured: Days 2, 4-16, 28, 180

  9. Number of Participants With Fever

    The occurrence of fever defined as greater than or equal to 38°C (100.4° F) measured at least 2 times at least 4 hours apart

    Measured: Days 2, 4-16, 28, 180

Secondary outcomes (2)
  1. Number of Participants With Detected Viremia

    RNAemia measurement by PCR through Day 28 post-challenge. RNA detection is in Cycle threshold (Ct). Viremia is determined by the presence of dengue virus RNA through Day 28 post-challenge. (Was viremia detected?)

    Measured: Days 2, 4-16, 28

  2. Microneutrilization (50%) Geometric Mean Titer

    Microneutrilization (50%) Geometric Mean Titer Dengue antibodies

    Measured: Day 28

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted7 Mar 2022
  2. Study start28 Feb 2022
  3. Primary completion4 Jan 2024
  4. Study completion4 Jan 2024

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Basic science
Allocation
Non-randomised
Intervention model
Sequential
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05268302
Sponsor's protocol ID
HP-00087533
Status last verified
Apr 2025
First submitted
9 Feb 2022
Last updated
17 Apr 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Chua JV, Price A, Sharaf S, Camacho Ortega S, Bernal PJ, Butler L, Koudjra AR, Joshi S, Hardy CSC, Currier JR, Waickman AT, Cairo C, Friberg H, Edelman R, Lyke KE. Novel dengue serotype 4 live virus human challenge: a phase 1 dose optimisation and homologous rechallenge study. Lancet Microbe. 2026 Oct 29:101542. doi: 10.1016/j.lanmic.2026.101542. Online ahead of print.

    PubMed 42956783

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose and Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge in people with Dengue, run by University of Maryland, Baltimore at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 32 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Apr 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 17 Apr 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With Solicited Injection Site Adverse Events (time frame: Days 1-7 post-challenge). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05268302, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Apr 2025.

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