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

NCT04786457 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: HP-00088798
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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.

Conditions

Dengue

Outcome Measures

Primary Outcomes (9)

• 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

  Days 2, 4, 5, 6, and 7

• 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

  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)

• 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

  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)

• 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

  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)

• 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.

  Days 1-16

• 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

  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)

• 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

  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)

• Number of Participants With Long-Term SAEs

  Number of participants with SAEs until 6 months post virus inoculation

  Days 2-180

• 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

  Days 2-28

Study Arms (1)

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

EXPERIMENTAL

open-label injection of DENV-1-LVHC to 15-20 adults who were previously vaccinated and 5 adults who have never received a dengue vaccination

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

Interventions

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

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

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.
• \. Tetravalent dengue antibody response at 28 days following final vaccination for vaccinated groups of volunteers.
• \. Volunteers must be able and willing 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 oophorectomy, or is post-menopausal).
• \. 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
• \. Provide consent for release of medical history records from primary care physician, college or university medical center, urgent care, or emergency room visit

You may not qualify if:

• \. Planned travel during the study period (180 days) which would interfere with the ability to complete all study visits
• \. 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
• \. Volunteer seropositive for hepatitis B surface antigen (HBsAg), hepatitis C virus antibodies (anti-HCV), or human immunodeficiency virus antibodies (anti-HIV)
• \. Unvaccinated volunteers positive for antibodies to flaviviruses (FV) to include dengue virus, West Nile virus, Yellow Fever virus, Zika virus, and Japanese encephalitis virus.
• \. 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)
• \. Medical history of, or current, diabetes, chronic obstructive pulmonary disease, peptic ulcer disease, coronary artery disease, cardiac arrhythmia, cardiomyopathy, pericarditis, or auto-immune disease
• \. 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)
• \. History of Guillain-Barré syndrome (GBS)
• \. 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
• \. Women who intend to become pregnant or men who intend to father a child during the study period (approximately 6 months)
• \. 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.
• \. Female volunteers using an intrauterine device (IUD) or Mirena®
• \. 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
• \. 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

Sponsors & Collaborators

• University of Maryland, Baltimore: lead
• United States Army Medical Materiel Development Activity: collaborator
• 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

Related Publications (1)

• 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.

  PMID: 38679035 DERIVED

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

klyke@som.umaryland.edu

410-706-5328

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: November 24, 2020
• First Posted: March 8, 2021
• Study Start: November 30, 2020
• Primary Completion: July 9, 2021
• Study Completion: July 9, 2021
• Last Updated: February 27, 2025
• Results First Posted: February 27, 2025

Record last verified: 2025-02

Locations

US (1)