AzTrials
AzTrials

DenguePhase 1NCT04786457

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

A Phase 1 study testing Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) 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 the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. 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 1 Live Virus Human Challenge (DENV-1-LVHC)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
10 participants
Where
1 siteUnited States
Study dates
30 Nov 2020to 9 Jul 2021
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

  • 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).
Show all 11Show fewer
  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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.

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: A Phase 1, Open-Label Clinical Trial With Dengue-1-Virus Live Virus Human Challenge (DENV-1-LVHC) Assessment of Healthy U.S. Adults Previously Primed With Tetravalent Dengue Virus Purified Inactivated Vaccine (TDEN-PIV) and Boosted With Tetravalent Dengue Virus Live Attenuated Vaccine Formulation (TDEN LAV)

The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge.

Read the detailed description

The purpose of this research study is to test the protection of volunteers previously vaccinated with Tetravalent Dengue Virus (TDEN) Purified Inactivated Vaccine (PIV) with alum and boosted with TDEN live attenuated vaccine (LAV) formulation against a weakened form of an experimental dengue virus challenge. The Investigators will also include people that have not received the study vaccine. The Investigators are collecting information about how the vaccine protects against a dengue virus challenge as well as adding to knowledge about the safety of the challenge. The information will help Investigators develop vaccines to protect people from dengue. Participation is voluntary. The duration of participation will last for 180 days (six months). After participants are exposed to the weakened dengue virus, the Investigators 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 a participant does develops symptoms, the Investigators will monitor him/her closely in a local hotel or a wing of our hospital to ensure safety and to treat symptoms if they occur. Participants will be compensated for their time.

Conditions
Dengue
Being tested
Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)
Medical subject headings
Dengue

What participants receive

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

  • Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)Biological

    one subcutaneous injection of Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) at 0.5 mL of 6.5 x 10^3 PFU/mL

Study groups in NCT04786457
Study groupRoleWhat they receive
Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)Experimentalopen-label injection of DENV-1-LVHC to 15-20 adults who were previously vaccinated and 5 adults who have never received a dengue vaccination
Receives: Biological: Dengue 1 Live Virus Human Challenge (DENV-1-LVHC)

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

    Number of Participants with Solicited Injection Site Erythema - solicited injection site adverse event until 7 days post virus inoculation

    Measured: Days 2, 4, 5, 6, and 7

  2. Number of Participants With Unsolicited Injection Site Adverse Events

    Number of Participants with Injection site pain - unsolicited injection site adverse events until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4, 5-16, 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)

  3. Number of Participants With Solicited Systemic Adverse Events

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

    Measured: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)

  4. Number of Participants With Incidence of Abnormal Laboratory Measurements

    Number of participants with incidence of abnormal laboratory measurements until 28 days post virus inoculation or 7 days post hospitalization, whichever is later

    Measured: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)

  5. Dengue-Related Illness Index

    Scales:

    Clinical Symptoms: None=0, Mild=1, Moderate=2, Severe=3 (Min Score=0, Max=3) Laboratory Abnormalities: None=0, Mild=1, Moderate=2, Severe=3 based on modified FDA CBER laboratory scale (per protocol) (Min=0, Max=3) Symptoms (Clinical symptoms or Laboratory Abnormalities) duration: 1 point/day (Day 1-16) (Min=0, Max=16) Subscale A (Symptom Duration): 1 point/day (Day 1-16) across 10 Clinical/Laboratory findings (Min = 0, Max = 160) Subscale B (Symptom # per day): 1 point/ Clinical/Laboratory finding (n=10) per day across 16 days Min=0, Max=160 Subscale C (Max Severity Score/day): None=0, Mild=1, Moderate=2, Severe=3 across 16 days: Min=0, Max=48 Total Range in DII score (total scale) which equates to subscale (A + B + C)/3: Min=0, Max=122.7

    https://doi.org/10.1016/s1473-3099(24)00100-2.

    Measured: Days 1-16

  6. Number of Participants With Unsolicited Systemic Adverse Events

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

    Measured: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)

  7. Number of Participants With Short-Term SAEs

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

    Measured: Days 2, 4-16, 19, 22, 25, and 28 (until 28 days post virus inoculation or 7 days post hospitalization, whichever is later, up to a maximum of 28 days)

  8. Number of Participants With Long-Term SAEs

    Number of participants with SAEs until 6 months post virus inoculation

    Measured: Days 2-180

  9. Number of Participants With Persistent Fever

    Number of participants with persistent 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 2-28

Timeline

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

  1. First posted8 Mar 2021
  2. Study start30 Nov 2020
  3. Primary completion9 Jul 2021
  4. Study completion9 Jul 2021

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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04786457
Sponsor's protocol ID
HP-00088798
Status last verified
Feb 2025
First submitted
24 Nov 2020
Last updated
27 Feb 2025
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No

Publications

  • Lyke KE, Chua JV, Koren M, Friberg H, Gromowski GD, Rapaka RR, Waickman AT, Joshi S, Strauss K, McCracken MK, Gutierrez-Barbosa H, Shrestha B, Culbertson C, Bernal P, De La Barrera RA, Currier JR, Jarman RG, Edelman R. Efficacy and immunogenicity following dengue virus-1 human challenge after a tetravalent prime-boost dengue vaccine regimen: an open-label, phase 1 trial. Lancet Infect Dis. 2024 Aug;24(8):896-908. doi: 10.1016/S1473-3099(24)00100-2. Epub 2024 Apr 25.

    PubMed 38679035

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dengue 1 Live Virus Human Challenge (DENV-1-LVHC) 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 11 inclusion and 26 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 27 Feb 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 27 Feb 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 2, 4, 5, 6, and 7). 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 NCT04786457, 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 27 Feb 2025.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in