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

NCT05268302 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HP-00087533
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Dengue

Outcome Measures

Primary Outcomes (9)

• Number of Participants With Solicited Injection Site Adverse Events

  solicited injection site adverse events until 7 days post virus inoculation

  Days 1-7 post-challenge

• 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

  Days 2, 4-16, 28

• 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

  Days 2, 4-16, 28

• Incidence of Abnormal Laboratory Measurements

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

  Days 2, 4-16, 28

• 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

  Days 2, 4-16, 28

• 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

  Days 2, 4-16, 28

• Number of Participants With Short-Term SAEs

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

  Days 2, 4-16, 28

• Number of Participants With Long-Term SAEs

  Number of SAEs until 6 months post virus inoculation

  Days 2, 4-16, 28, 180

• 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

  Days 2, 4-16, 28, 180

Secondary Outcomes (2)

• Number of Participants With Detected Viremia

  Days 2, 4-16, 28

• Microneutrilization (50%) Geometric Mean Titer

  Day 28

Study Arms (2)

Low Dose Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Primary

EXPERIMENTAL

0.95 x 10\^2 Plaque Forming Units

Biological: Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose

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

EXPERIMENTAL

0.95 x 10\^2 Plaque Forming Units

Biological: Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge

Interventions

Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose BIOLOGICAL

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

Low Dose Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Primary

Dengue 4 Live Virus Human Challenge (DENV-4-LVHC) - Low Dose - Homologous Rechallenge BIOLOGICAL

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.

Also known as: Homologous Rechallenge

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

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• Medical Technology Enterprise Consortium (MTEC): collaborator

Study Sites (1)

University of Maryland, Baltimore, Center for Vaccine Development and Global Health

Baltimore, Maryland, 21201, United States

Location

MeSH Terms

Conditions

Dengue

Condition Hierarchy (Ancestors)

Mosquito-Borne Diseases; Vector Borne Diseases; Infections; Arbovirus Infections; Virus Diseases; Flavivirus Infections; Flaviviridae Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Results Point of Contact

• Title: Kirsten E. Lyke, MD
• Organization: University of Maryland, Baltimore Center for Vaccine Development and Global Health (CVD)

klyke@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator, Professor of Medicine

Study Record Dates

• First Submitted: February 9, 2022
• First Posted: March 7, 2022
• Study Start: February 28, 2022
• Primary Completion: January 4, 2024
• Study Completion: January 4, 2024
• Last Updated: April 17, 2025
• Results First Posted: April 17, 2025

Record last verified: 2025-04

Locations

US (1)